Use Of 3D-CRT Research Articles

Evaluating the Effects of Prostate Radiotherapy Intensified with Pelvic Nodal Radiotherapy and Androgen Deprivation Therapy on Myelosuppression: Single-Institution Experience.

Prostate cancer (PCa) management commonly involves the utilization of prostate radiotherapy (PRT), pelvic nodal radiotherapy (PNRT), and androgen deprivation therapy (ADT). However, the potential association of these treatment modalities with bone marrow (BM) suppression remains inadequately reported in the existing literature. This study is designed to comprehensively evaluate the risk of myelosuppression associated with PRT, shedding light on an aspect that has been underrepresented in prior research. We conducted a retrospective analysis of 600 patients with prostate cancer (PCa) treated with prostate radiotherapy (PRT) at a single oncology center between 2007 and 2017. Patients were categorized into four cohorts: PRT alone (n = 149), PRT + ADT, (n = 91), PRT + PNRT (n = 39), and PRT + PNRT + ADT (n = 321). To assess the risk of myelosuppression, we scrutinized specific blood parameters, such as hemoglobin (HGB), white blood cells (WBCs), neutrophils (NEUT), lymphocytes (LYM), and platelets (PLT) at baseline, mid-treatment (mRT), immediately post-RT (pRT), 1 month post-RT (1M-pRT), and 1 year post-RT (1Y-pRT). The inter-cohort statistical significance was evaluated with further stratification based on the utilized RT technique {3D conformal radiotherapy (3D-CRT), and intensity-modulated radiation therapy (IMRT)}. Significant statistical differences at baseline were observed in HGB and LYM values among all cohorts (p < 0.05). Patients in the PRT + PNRT + ADT cohort had significantly lower HGB at baseline and 1M-pRT. In patients undergoing ADT, BMS had a significant impact at 1M-pRT {odds ratio (OR) 9.1; 95% Confidence Interval (CI) 4.8-17.1} and at 1Y-pRT (OR 2.84; CI 1.14-7.08). The use of 3D-CRT was linked to reduced HGB levels in the PRT + PNRT + ADT group at 1 month pRT (p = 0.015). Similarly, PNRT significantly impacted BMS at 1M-pRT (OR 6.7; CI 2.6-17.2). PNRT increased the odds of decreased WBC counts at 1Y-pRT (OR 6.83; CI: 1.02-45.82). Treatment with any RT techniques (3D-CRT or IMRT), particularly in the PRT + PNRT and PRT + PNRT + ADT groups, significantly increased the odds of low LYM counts at all time points except immediately pRT (p < 0.05). Furthermore, NEUT counts were considerably lower at 1M-pRT (p < 0.05) in the PRT + PNRT + ADT group. PLT counts were significantly decreased by PRT + PNRT + ADT at mRT (OR 2.57; 95% CI: 1.42-4.66) but were not significantly impacted by the RT technique. Treatment with PRT, ADT, PNRT, and 3D-CRT is associated with BMS. Despite this statistically significant risk, no patient required additional interventions to manage the outcome. While its clinical impact appears limited, its importance cannot be underestimated in the context of increased integration of novel systemic agents with myelosuppressive properties. Longer follow-up should be considered in future studies.

Hybrid VMAT-3DCRT as breast cancer treatment improvement tool

Radiation therapy is an important tool in the treatment of breast cancer and can play a crucial role in improving patient outcomes. For breast cancer, if the technique has been for a long time the use of 3DCRT, clinicians have seen the management evolve greatly in recent years. Field-in-field and IMRT approaches and more recently dynamic arctherapy are increasingly available. All of these approaches are constantly trying to improve tumour coverage and to preserve organs at risk by minimising the doses delivered to them. If arctherapy allows a considerable reduction of high doses received by healthy tissues, no one can deny that it also leads to an increase of low doses in tissues that would not have received any with other techniques. We propose a hybrid approach combining the robustness of the 3DCRT approach and the high technicality and efficiency of arctherapy. Statistical tests (ANOVA, Wilcoxon, determination coefficient, ROC, etc.) allow us to draw conclusions about the possibility of using the hybrid approach in certain cases (right breast, BMI > 23, age > 48, target volume > 350 cc, etc.). Depending on the breast laterality and patients morphological characteristics, hybridization may prove to be a therapeutic tool of choice in the management of breast cancer in radiotherapy.

Myocardial Infiltration in Primary Mediastinal B-Cell Lymphoma Detected by Cardiac Magnetic Resonance Imaging

Introduction: Cardiac involvement, particularly myocardial infiltration in primary mediastinal lymphoma, is a rare occurrence with an incidence of only 9% in known cases of primary malignancy. Neoplasm infiltration into the myocardium manifests through direct invasion, hematogenous spread, transvenous invasion through the great veins, or lymphangitic spreading in the mediastinal. Myocardial infiltration in lymphoma presents a grim prognosis and its treatment may be associated with specific risks, such as myocardial rupture. Various imaging modalities may detect cardiac involvement, with cardiac magnetic resonance (CMR) imaging considered the gold standard. CMR enables clear delineation of myocardial infiltration, making it valuable for local staging, pretreatment planning, and evaluating treatment response. Case Presentation: : A 37-year-old woman patient was diagnosed with primary mediastinal large B-cell lymphoma. Mild chest discomfort and shortness of breath were observed 3 months before hospital admission. A thorax CT scan showed a heterogeneous contrast-enhancing mass with a central necrotic area in the anterior mediastinum. Following thoracotomy and tumor debulking, the patient complained of severe crushing chest pain radiating to her back, accompanied by new T wave inversion on ECG and elevated cardiac troponin levels a week after surgery. Coronary angiogram results showed a normal coronary artery. Subsequent cardiac MRI showed tumor infiltration into the anterior pericardial space, as well as the myocardium of the left and right ventricles. Chemotherapy was promptly initiated, resulting in a gradual improvement of symptoms. Conclusions: In this study, we discuss the use of 3D-CRT in the re-irradiation of NPC with its limitation on obtaining optimum dose sculpture compared to more sophisticated and widely spread modalities like IMRT. However, with careful planning, we can still obtain optimum tumor dose, minimize OAR dose, and subsequently late toxicities that come after. We hope that this study can bring hope to centers with limited facilities, and we suggest further studies on reirradiation, especially in OAR dose tolerance guidelines.

Cardiac dose in the treatment of synchronous bilateral breast cancer patients between three different radiotherapy techniques (VMAT, IMRT, and 3D CRT)

PurposeSynchronous bilateral irradiation of both mammary glands and chest wall is a challenging task due to technical difficulties and limited evidence supporting an optimal technique to improve treatment outcomes. We studied and compared the dosimetry data of three radiotherapy techniques to select the most optimal one.MethodsWe compared three-dimensional conformal radiation treatment (3D CRT), intensity-modulated radiation therapy (IMRT), and volumetric modulated arc therapy (VMAT) during irradiation of synchronous bilateral breast cancer in nine patients followed by examination of dose distribution to the cardiac conduction system (SA node, AV node and Bundle of His), myocardium, lungs, left anterior descending artery (LADA) and right coronary artery (RCA) .ResultsVMAT is the most sparing technique for SBBC treatment. Even though doses to the SA node, AV node and Bundle of His were higher with VMAT (Dmean were 3.75 ± 0.62, 2.58 ± 0.83 and 3.03 ± 1.18 Gy respectively) compared with 3D CRT (Dmean were 2.61 ± 0.66, 1.52 ± 0.38 and 1.88 ± 0.70 Gy respectively), this difference is statistically insignificant. Doses to the right and left lung (average Dmean = 12.65 ± 3.20 Gy, V20Gy = 24.12 ± 6.25%), myocardium (Dmean = 5.33 ± 1.51 Gy, V10Gy = 9.80 ± 3.83%, V20Gy = 7.19 ± 3.15%, V25Gy = 6.20 ± 2.93%), and LADA (Dmean = 10.04 ± 4.92 Gy, V20Gy = 18.17 ± 13.24% and V25Gy = 15.41 ± 12.19%) were highest with 3D CRT. The highest Dmean in the cardiac conduction system (5.30 ± 2.23, 3.15 ± 1.61 and 3.89 ± 1.85 Gy respectively) was observed with IMRT, and a similar effect was noted in RCA (Dmean = 7.48 ± 2.11 Gy).ConclusionVMAT is the optimal and satisfactory radiation therapy technique for sparing organs at risk (OARs). With VMAT, a lower Dmean value was noted in the myocardium, LADA, and lungs. The use of 3D CRT significantly increases the dose of radiation reaching the lungs, myocardium, and LADA, which can subsequently cause cardiovascular and lung complications, but not in the cardiac conduction system.

Explainable Artificial Intelligence for Identification of Dosimetric Predictors of Radiation Toxicity: A Secondary Analysis of RTOG 0617

<h3>Purpose/Objective(s)</h3> Dosimetric predictors of toxicity in patients treated with definitive chemoradiation (CRT) for locally advanced non-small cell lung cancer have been identified, though these are often identified through trial and error or difficult to understand statistical methods. This study utilizes machine learning (ML) evaluated using explainable artificial intelligence (EAI) techniques to empirically characterize dosimetric predictors of toxicity in patients with LA-NSCLC treated with CRT as part of a prospective clinical trial. <h3>Materials/Methods</h3> A secondary analysis was performed to utilize ML EAI to identify dosimetric predictors of treatment-related toxicity in the RTOG 0617 trial. We trained a machine-learning based, gradient-boosted tree (GBT) models of ≥ grade 3 pulmonary, cardiac, and esophageal toxicities using Zubrod performance status, T stage, N stage, group stage, radiation technique, receipt of cetuximab, receipt of consolidative chemotherapy, and available dosimetric parameters. Shapley additive explanation (SHAP) values based on the GBT models were used to identify inflection points to select dosimetric thresholds. Identified thresholds were validated using univariate (UVA) and multivariable (MVA) logistic regression. <h3>Results</h3> Of the patients included on the trial, 471 patients had available dosimetry data. A total of 27 (5.7%), 56 (11.9%), and 45 (9.6%) patients experienced ≥ grade 3 pulmonary, esophageal, and cardiac toxicities, respectively. For pulmonary toxicities, using SHAP plots, lung V5≥57% and ≥82% were identified as an inflection points predictive of pneumonitis, which was validated using MVA, with odds ratios (OR) of 4.04 (p=0.004) and 5.11 (p=0.009), respectively. Upon inspection of lung V20, values ≥30% (OR: 3.23; p=0.011) and ≥39% (OR: 5.42; p=0.003) were predictive. Using mean lung dose, values ≥21 Gy were associated with increased toxicity (OR: 3.52; p=0.004). Use of 3DCRT was significantly associated with increased pneumonitis only in the V5 ≥57%, V5 ≥82%, V20 ≥39% MVAs. When assessing esophagitis, esophagus V20 ≥36% (OR: 4.76; p=0.010) and ≥74% (OR: 4.82; p=0.002) were associated with increased risk, as were mean values ≥21 Gy (OR: 4.66; p=0.004) and ≥32 Gy (OR: 3.30; p<0.001). In all of these analyses, radiation technique did not have a significant impact but receipt of consolidative chemotherapy was protective against esophagitis. On evaluation of cardiac dosimetric parameters, only heart V40 ≥57% (OR: 2.04; p=0.032) was predictive of cardiotoxicity. Only group stage was also significantly associated with cardiotoxicity. <h3>Conclusion</h3> Using validation with logistic regression, we demonstrated the feasibility of ML EAI approaches to identify dosimetric predictors of toxicity. Using this method, new dosimetric thresholds were identified, pending validation in larger datasets. Our findings support the utilization of ML EAI for empiric determination of radiation treatment planning considerations.

Quality of Life Analysis of a Phase II Randomized Controlled Trial Comparing 3D-Conformal Radiotherapy (3D-CRT) and Intensity Modulated Radiotherapy (IMRT) in Locally Advanced Rectal Cancer (TRI-LARC)

<h3>Purpose/Objective(s)</h3> The aim of the study was to compare the use of 3D-CRT and IMRT in pre-operative long course chemo-radiotherapy for locally advanced rectal cancer. We herein evaluate the impact of the two treatment modalities on quality of life (QOL), a secondary objective of the study. <h3>Materials/Methods</h3> 94 patients with rectal adenocarcinoma were enrolled in a prospective randomized phase II trial across three institutions between 2014 and 2020. Eligible patients had stage T3-4, N(any) or circumferential resection margin at risk with no evidence of metastatic disease. All patients were prescribed 50.4Gy in 28 fractions with concomitant 5-fluorouracil or capecitabine. Patients were randomly assigned (1:1) to 3D-CRT and IMRT planning techniques. QOL was assessed using the EORTC QLQ C30 and QLQ CR29 questionnaires at baseline, during the final week of radiotherapy and at six and twelve months after radiotherapy. A paired sample t test was used to compare differences in QOL from baseline to each follow-up. One-way between-group analyses of covariance (ANCOVA) were conducted to compare the effect of the trial arms on each QOL score. <h3>Results</h3> At a median follow-up of 14 months, the trial was terminated early due to failure to establish efficacy in the primary outcome, acute gastrointestinal toxicity. The median age was 59 years and 72/94 (77%) were male. 86/94 (91%) patients completed the baseline and at least one other QOL assessments. QOL data at one year was available in 55/94(58%). At baseline, there was no difference in QOL scores between trial arms. Overall, emotional functioning had improved at six months but physical, cognitive, role and social functioning had declined. At six months, there was a significant improvement in constipation, blood and mucous in stool, bloating, urinary frequency, buttock pain and anxiety scores compared to baseline. There was a significant deterioration in dyspnea, fatigue, nausea/vomiting, taste, hair loss, erectile dysfunction, body image and global health scores from baseline to 6-month follow-up. After adjusting for pre-intervention score, the IMRT arm had better physical functioning (p=0.038) and role functioning (p=0.014) during the final week of radiotherapy compared to the 3DCRT arm. The end of radiotherapy embarrassment score, for those without a stoma, was significantly worse in the IMRT arm (p=0.032). There was no other significant difference in QOL scores between the two arms, at either the final week of radiotherapy or at 6 months, after adjustment for pre-intervention scores. The limitations of the study include its early termination, the potential for type 1 error and the possible influence of other factors on QOL data such as chemotherapy and postoperative complications. <h3>Conclusion</h3> There are limited QOL benefits of IMRT compared to 3D-CRT in the neoadjuvant setting for rectal cancer.

Real World Rates and Predictive Factors of Pneumonitis in Advanced, Non-Resectable NSCLC Treated with Concurrent Chemoradiation and Durvalumab

<h3>Purpose/Objective(s)</h3> Real world outcomes related to pneumonitis in patients with locally advanced (LA) non-resectable non-small cell lung cancer (NSCLC) treated with concurrent chemoradiation (chemoRT) and consolidative durvalumab (D) may differ from those seen in prospective trials given selection biases and other variables in clinical trials. We aimed to assess the real-world incidence of pneumonitis for LA NSCLC patients and identify clinical or dosimetric predictors of pneumonitis. <h3>Materials/Methods</h3> We retrospectively identified consecutive patients with locally advanced NSCLC treated with chemoRT and D at a single institution from 4/2017 to 6/2019 from our prospectively maintained institutional database. The actuarial incidence of pneumonitis was estimated using the Kaplan-Meier method and compared using log-rank tests. Toxicity was evaluated via retrospective examination of clinical documents and prescription records (i.e., steroids or oxygen) and graded according to Common Terminology Criteria for Adverse Events, version 5.0. Logistic regression was used to assess associations between pneumonitis and relevant clinical and dosimetric variables. Patients were followed with clinical examination and surveillance computed tomography scans every 3 months for 2 years and every 6 months afterwards. <h3>Results</h3> We identified 61 patients with locally advanced NSCLC that were consecutively treated with a median RT dose of 66 Gy (range 60-70Gy). Median follow up was 29 months (range 4-55). Intensity-modulated radiation therapy (IMRT) was used in 36 (59%) patients, and 25 (41%) patients received 3D-conformal RT (3DCRT). Twenty-three (37.7%) patients developed pneumonitis. Highest grade pneumonitis was 2 (n=17, 27.9%), and 3 (n=5, 8.2%). Of patients who developed pneumonitis, the median time to onset was 3.2 months from completion of RT (range 1.2-9.1), with a 1-year actuarial rate of 43.5% for all grade pneumonitis. On logistic regression, significant predictors of any grade pneumonitis were higher mean lung dose, V5, V10, V15, V20 and V25. There was no association between time to pneumonitis and the volume of the planning target volume (PTV) or use of 3DCRT vs IMRT (p > 0.05). <h3>Conclusion</h3> In real-world patients with locally advanced NSCLC treated with concurrent chemoRT and consolidative durvalumab, the incidence of any grade and grade 3 pneumonitis may be higher than previously observed in prospective clinical trials. Several dosimetric parameters (MLD, V5, V10, V15, V20 and V25) predicted development of pneumonitis, emphasizing the global importance of minimizing dose to normal lung tissue.

Re-Irradiation of Recurrent Nasopharyngeal Cancer: A 4-year Follow-up Study of Treatment using 3-Dimensional Conformal Radiotherapy

Introduction: Nasopharyngeal cancer (NPC) is a prevalent diagnosis of head and neck cancers (HNC) in Asia. In Indonesia, it is estimated that there are 12,000 new cases per year. Case Presentation: The author reports a 25-year-old male patient with recurrent NPC. This patient was first diagnosed with NPC stage IVB in 2013 and was treated by chemoradiation. In 2016, he found another mass in his neck. The biopsy result showed the recurrence of the NPC with histopathology of Undifferentiated carcinoma (WHO type III). Re-irradiation was planned, and the patient subsequently received 3D-Conformal Radiotherapy (3D-CRT) at our department. Four years after the completion of re-irradiation, the patient was alive and well with no signs of recurrence but still complained about late toxicities like trismus and fibrotic neck. Conclusions: In this study, we discuss the use of 3D-CRT in the re-irradiation of NPC with its limitation on obtaining optimum dose sculpture compared to more sophisticated and widely spread modalities like intensity-modulated radiotherapy (IMRT). However, with careful planning, we can still obtain optimum tumor dose, minimize organs at-risk (OAR) dose, and subsequently late toxicities that come after. We hope that this study can bring hope to centers with limited facilities, and we suggest further studies on re-irradiation, especially in OAR dose tolerance guidelines.

Cervical cancer patient reported gastrointestinal outcomes: intensity/volumetric modulated vs. 3D conformal radiation therapy.

ObjectiveTo evaluate gastrointestinal (GI) patient reported outcomes (PROs) in cervical cancer patients treated with definitive radiotherapy (RT), comparing 3D conformal RT (3DCRT) vs. intensity modulated/volumetric modulated arc therapy (IMRT/VMAT).MethodsAn analysis of patients treated with definitive RT between 2015–2018 was performed. GI PROs were prospectively collected at baseline, during RT (acute), ≤12 weeks after RT (subacute), and >12 weeks after RT (late). GI PROs evaluated three symptom domains: bowel problems (BPs), bowel bother (BB), and abdominal problems (APs). Multiple linear regression analysis was performed to investigate associations between mean changes of symptom scores with clinical and dosimetric variables.ResultsThe cohort included 167 patients. A total of 100 (60%) patients were treated with IMRT/VMAT and 67 (40%) with 3DCRT. In the subacute phase, the mean change of symptom scores from baseline in 3DCRT vs. IMRT/VMAT were +0.9 vs. −1.15 (p=0.004) for BP, +2.18 vs. −0.10 (p=0.019) for BB, and +1.41 vs. −0.38 (p=0.021) for AP. Likewise, in the late phase, mean changes were +0.72 vs. −0.82 (p=0.014) for BP, +1.98 vs. −0.03 (p=0.008) for BB, and +1.29 vs. −0.31 (p<0.001) for AP. On multiple linear regression, use of 3DCRT vs. IMRT/VMAT was associated with greater mean changes in subacute BP (p=0.023) and late phase AP (p=0.019). A higher small bowel V50Gy was associated increased symptom scores in late AP (p=0.012).Conclusion3DCRT was associated with significantly greater worsening of GI PRO symptom scores in the subacute and late phase. These data support the ongoing use of IMRT/VMAT in routine practice.

Dosimetric evaluation of SBRT treatment plans of non-central lung tumours: clinical experience

AbstractObjectives:Lung cancer is the most commonly diagnosed cancer in Canada and the leading cause of cancer-related mortality in both men and women in North America. Surgery is usually the primary treatment option for early-stage non-small cell lung cancer (NSCLC). However, for patients who may not be suitable candidates for surgery, stereotactic body radiation therapy (SBRT) is an alternative method of treatment. SBRT has proven to be an effective technique for treating NSCLC patients by focally administering high radiation dose to the tumour with acceptable risk of toxicity to surrounding healthy tissues. The goal of this comprehensive retrospective dosimetric study is to compare the dosimetric parameters between three-dimensional conformal radiation therapy (3DCRT) and volumetric-modulated arc therapy (VMAT) lung SBRT treatment plans for two prescription doses.Methods:We retrospectively analysed and compared lung SBRT treatment plans of 263 patients treated with either a 3DCRT non-coplanar or with 2–3 VMAT arcs technique at 48 Gy in 4 fractions (48 Gy/4) or 50 Gy in 5 fractions (50 Gy/5) prescribed to the planning target volume (PTV), typically encompassing the 80% isodose volume. All patients were treated on either a Varian 21EX or TrueBeam linear accelerator using 6-MV or 10-MV photon beams.Results:The mean PTV V95% and V100% for treatment plans at 48 Gy/4 are 99·4 ± 0·6% and 96·0 ± 1·0%, respectively, for 3DCRT and 99·7 ± 0·4% and 96·4 ± 3·4%, respectively, for VMAT. The corresponding mean PTV V95% and V100% at 50 Gy/5 are 99·0 ± 1·4% and 95·5 ± 2·5% for 3DCRT and 99·5 ± 0·8% and 96·1 ± 1·6% for VMAT. The CIRI and HI5/95 for the PTV at 48 Gy/4 are 1·1 ± 0·1 and 1·2 ± 0·0 for 3DCRT and 1·0 ± 0·1 and 1·2 ± 0·0 for VMAT. The corresponding CIRI and HI5/95 at 50 Gy/5 are 1·1 ± 0·1 and 1·3 ± 0·1 for 3DCRT and 1·0 ± 0·1 and 1·2 ± 0·0 for VMAT. The mean R50% and D2cm at 48 Gy/4 are 5·0 ± 0·8 and 61·2 ± 7·0% for 3DCRT and 4·9 ± 0·8 and 57·8 ± 7·9% for VMAT. The corresponding R50% and D2cm at 50 Gy/5 are 4·7 ± 0·5 and 65·5 ± 9·4% for 3DCRT and 4·7 ± 0·7 and 60·0 ± 7·2% for VMAT.Conclusion:The use of 3DCRT or VMAT technique for lung SBRT is an efficient and reliable method for achieving dose conformity, rapid dose fall-off and minimising doses to the organs at risk. The VMAT technique resulted in improved dose conformity, rapid dose fall-off from the PTV compared to 3DCRT, although the magnitude may not be clinically significant.

Hematological Changes Associated With Prostate Radiotherapy And Androgen Deprivation Therapy

Prostate cancer (PCa) is often managed with prostate radiotherapy (PRT), pelvic nodal radiotherapy (PNRT), and androgen deprivation therapy (ADT). Both PNRT and ADT are thought to place patients at risk for myelosuppression. The interaction and duration of PRT, PNRT, ADT, and RT technique (3D-CRT versus IMRT) on myelosuppression is not well characterized in PCa patients. This study sought to address this uncertainty. A single-institution retrospective analysis of 600 PCa patients treated with PRT (between 2007-2017) was conducted. Patients were stratified into four groups: PRT alone (group-1), PRT and PNRT (group-2), PRT and ADT (group-3), and PRT, PNRT, and ADT (group-4). Hemoglobin (HGB), white blood cells (WBC), neutrophils, and platelets (PLTs) were extracted from baseline (prior to RT), mid-RT, at RT end, one-month post-RT, and one-year post-RT. Chi-Square tests were performed to test differences between groups. Additionally, hematologic values were stratified by the RT technique. A total of 600 patients were identified in this study for the final analysis. Although bone marrow suppression (BMS) was associated with Group 2, 3, and 4. Only Group 4 (N = 321) showed persistent decreased HGB one-month post-treatment. The addition of ADT was associated with an Odds-Ratio (OR) of 2.43 (CI:1.33-4.35, P<0.004) and that of PNRT with an OR of 3.24 (CI:1.76-5.74, P<0.001). Decreased WBCs were observed in all groups, with PNRT carrying the highest impact with an OR of 2.23 (CI:1.12-4.50, P<0.023). Neutrophil counts were decreased in all groups, with PNRT carrying an OR of 4.69 (CI:3.02-7.27, P<0.001). Both WBC and neutrophil recuperated at four weeks post-PRT in all groups. IMRT was associated with lower BMS than 3DCRT. Our analysis did not identify a statistically significant decrease in platelet count in all groups. Importantly, no patient required intervention for the myelosuppression. Our study suggests that prostate RT, ADT, and the use of 3D-CRT vs. IMRT is associated with mild myelosuppression. The myelosuppression is mild and transient with most patients recuperating to their baseline at four weeks post-radiation therapy. Longer follow up, and patient-reported outcomes should be considered in future studies to determine if these changes are clinically significant.

National Variation in Radiation Oncology Procedures

Significant variation in clinical practice exists in the US healthcare system, particularly with regard to well-reimbursed procedures. Predictors of radiotherapy (RT) procedures and technologies, however, remain poorly characterized. We hypothesized that provider gender, practice rurality, practice region, and length of experience would predict for the use of specific RT procedures in the Medicare population. The Centers for Medicare and Medicaid Services (CMS) Physician and Other Supplier Public Use File (POSPUF), which includes all Healthcare Common Procedure Coding System (HCPCS) codes reimbursed by Medicare for individual physicians in 2016, was linked to the CMS Physician Compare database by National Provider Identifier (NPI). Entries that could not be linked or lacked our variables of interest were excluded. Covariates for multivariable regression analysis included provider gender (male vs female), practice rurality (metro vs non-metro), practice region (Midwest vs South vs West vs Northeast), and years since graduation. Treatment delivery HCPCS codes for 3D-conformal RT (3DCRT), intensity modulated RT (IMRT), stereotactic radiosurgery (SRS), stereotactic body RT (SBRT), low dose rate brachytherapy (LDR), and high dose rate brachytherapy (HDR) were evaluated as response variables. All fits were obtained via logistic regression. 1,802 physicians were available for analysis: 1,383 (76.7%) were male and 419 (23.3%) were female. 119 (6.6%) practiced in rural areas while 1683 (93.4%) practiced in metro areas. 378 (21.0%) providers practiced in the Midwest, 290 (16.1%) in the Northeast, 743 (41.2%) in the South, and 391 (21.7%) in the West. Mean time from medical school graduation was 26.56 years (SD 11.14). On multivariable regression analysis, male gender predicted for LDR use (OR 8.19, p<0.001), but not the use of other technologies, while metro practice predicted for greater utilization of HDR (OR 12.95, p=0.01). Use of 3DCRT was more likely in the South (OR 1.33, p<0.01) and the West (OR 1.38, p<0.01) than the Northeast whereas SRS was less common in the Midwest (OR 0.71, p<0.01), South (OR 0.49, p<0.001), and West (OR 0.43, p<0.001) relative to the Northeast. SBRT, on the other hand, was more commonly utilized in the Midwest (OR 2.63, p=0.03), South (OR 3.44, p<0.01), and West (OR 4.87, p<0.001) compared to the Northeast. HDR use was also greater in the Midwest (OR 1.97, p=0.02) and West (OR 1.87, p=0.03) compared to the Northeast. Longer practice experience was related to lower SBRT use (OR 0.98, p<0.001) and higher utilization of LDR (OR 1.02, p=0.02). Aside from LDR, gender does not influence procedure use, though adopting newer technology appears to be inversely related with experience. Substantial geographic variation in the use of specific RT technologies was identified. The degree to which this variation reflects effective care, preference-sensitive care, or supply-sensitive care warrants further investigation.

Conventional and Conformai Radiotherapy with and without Beam Intensity Modulation in Patients with Stage II Hodgkin's Lymphoma with Supradiaphragmal Lesions

Within the group treated with the conventional RT 19 (8.1 %) patients had recurrent disease. Overall 5- and 10-year survival (OS) was equal and accounted for 98.0 ± 1.4 %, the disease-free survival (DFS) was also equal between groups and accounted for 85.9 ± 1.3 %. The rate of 5- and 10-year OS in patients who received CF was 97.8 ± 1.7 %; the DFS rate for the same period was 85.0 ± 1.5 % with standard fractionation and 86.2 ± 1.6 % with MF (p &gt; 0.1). The total number of local radiation reactions and the number of radiation pulmonitis were significantly smaller with the exposure twice daily compared to CF at 2D planning and mantle irradiation. Decreasing the radiation volume from the mantle type to IFRT was shown to reduce the incidence of pulmonitis. The incidence of esophagitis remained the same with different fractionation and the irradiation volumes specified above. The results of the analysis proved the total absence of radiation pericarditis with both types of conformal RT with or without IMRT. No pulmonitis cases were observed with IMRT; the use of 3D-CRT and 2D-RT significantly increased the incidence of pulmonitis. The incidence of esophagitis within the CRT-group (n = 80) was 2 times lower compared to the conventional RT (22.5 % and 43.9 %; p &lt; 0.01). Conclusion. The innovative technologies of radiation therapy allowed to reduce the incidence of early local radiation reactions. These technologies will be the basis for preventing severe late radiation complications that reduce the life expectancy and quality of life of patients with HL.

Local Tumor Control After Stereotactic Body Radiation Therapy for Early Lung Cancer is Not Impacted by the Use of Intensity Modulated Radiation Therapy or Respiratory Gating

Though stereotactic body radiation therapy (SBRT) has become a standard treatment option for stage I NSCLC, the majority of published results relate to three-dimensional treatment planning (3D-CRT). Less data is available following treatment with IMRT, and there is also limited published experience using respiratory gating, where treatment is only delivered to a portion of the breathing cycle, during SBRT. Retrospective review of patients treated with SBRT for Stage I NSCLC between 2007 and 2015. All patients had a 4D simulation with the Varian RPMTM system and abdominal compression was used in the majority (81%). Respiratory gating was typically used if longitudinal tumor motion exceeded 1cm. Patient characteristics, treatment planning and delivery parameters, dosimetry information, and patient outcomes were collected and analyzed using SPSS statistical software (descriptive stats, bivariate procedures and survival analyses). A total of 297 patients (median age 71, range 43-89) with stage I NSCLC were included. Pathology was confirmed in 94.6% of patients. The majority of lesions were located in the upper lobes (60.9%) and clinical stage T1A (68%). The use of 3DCRT and IMRT planning was similar, 52% vs 48%, although an increased frequency of IMRT was noted in more recent years. Respiratory gating was employed in approximately 16% of cases (n=51). The gating cohort included 78% lower lobe tumors, while 26% of lesions treated without gating were in the lower lobes. The most common SBRT regimens were 48Gy in 4 fractions and 54-60Gy in 3 fractions. With a median follow up of 22.7 months, there were 17 local failures for a crude relapse rate of 5.7%. Local tumor relapse was similar in patients treated with 3DCRT and IMRT (6.5% vs 4.9%, p=0.962), and relapse likewise was similar with and without respiratory gating (7.8% vs 4.9%, p=0.560). In addition, T-stage, tumor size, pathology and SBRT regimen did not correlate with local tumor control. Overall survival for the entire population approximated 72% at 2 years. Treatment appeared tolerated well with 6 documented grade 3+ events, and thus there were too few events to compare toxicity amongst treatment cohorts. The utilization of respiratory gating or the use of IMRT does not appear to compromise the therapeutic ratio for patients treated with SBRT for stage I NSCLC.

Patterns of Dose Prescription and Recording in Stereotactic Body Radiation Therapy: A Multi-institutional Study

Hypofractionated stereotactic body radiation therapy (SBRT) has become standard of care for small inoperable lesions in many disease sites. Dose prescription and delivery play an important role; however there is no consistent way of reporting dose and treatment outcome (1). This study evaluates the variability in dose prescription and reporting among academic institutions. The SBRT data of 428 patients from 8 academic institutions were collected. Prescription and delivery parameters were examined such as treatment site, technique (3DCRT, IMRT, VMAT, etc.), treatment planning system, inhomogeneity correction algorithm, dose prescription, size of target volume, normalization and monitor unit (MU). The dose-volume histogram (DVH) for each patient was anonymously analyzed at a central location following international guidelines, ICRU-50 and ICRU-83 for 3DCRT and IMRT, respectively. Dose parameters; D100, D98, D95, D50, D2 were extracted for analysis of SBRT plan and variability among institutions. Use of 3DCRT, IMRT and VMAT was 12%, 31%, and 57%, respectively. Surprisingly every institution used same treatment planning and algorithm for dose calculation. Disease sites were mainly lung (71%) followed by liver (15.5%), prostate (7.5%), spine (6.8%), brain (4.1%), and pancreas (2.5%). Target volume in lung cases varied and largely fell into two groups (22.0-28.7) and (48.0-67.1) cm3 indicating differences in margin or selection of larger tumors. The MU was inversely proportion to the treatment volume. A hot spot ranging from 120-150% was noted in nearly half of the patients and was more specific to some institutions. A D50 ≥110% was found in nearly half of the institutions. Three of the four institutions that delivered D50 values <110% still had a difference between D50 and D98 of ≥10%, suggesting the relative dose distributions among these 3 institutions was similar in general to that of the other four with high D50 values. These same seven institutions had relatively high inhomogeneity index (HI) as summarized in Table 1. As shown by the large variation in dosimetry among academic institutions, a single dose parameter to characterize SBRT prescriptions in the literature or in guidelines can be very misleading. Large variation in volume indicates larger margin characteristics of institutional practice. An attempt to unify dose prescription and delivery is needed for outcome comparison as we move towards more hypofractionated treatments.

Efficacy of three-dimensional conformal radiotherapy combined with transarterial chemoembolization for hepatocellular carcinoma with portal vein tumor thrombus.

ObjectiveThe current study aimed to evaluate the efficacy and outcomes of three-dimensional conformal radiotherapy (3DCRT) combined with transarterial chemoembolization (TACE) for treating patients with hepatocellular carcinoma involving portal vein tumor thrombus.MethodsBetween January 2000 and December 2013, a total of 182 hepatocellular carcinoma patients with portal vein tumor thrombus were retrospectively analyzed: 68 patients were treated by 3DCRT alone (group A), 74 by TACE alone (group B), and 40 by a combination of 3DCRT + TACE (group C). The overall survival (OS) of the three groups was compared using the Kaplan–Meier method. The independent predictors of survival were identified using multivariate analysis.ResultsThe total effective rate (complete response + partial response) among all patients was 44% (80/182). The objective response rate (complete response + partial response) was higher in group C than in group A or B, but the differences were not significant. OS rates at 1, 2, and 3 years were significantly higher in group C than in group A or B (P<0.05), while OS rates were similar between groups A and B. Multivariate analysis identified serum levels of alpha-fetoprotein <400 ng/mL and the use of 3DCRT + TACE as independent predictors of better OS.ConclusionThese results suggest that combining 3DCRT with TACE may provide better OS than either technique alone in hepatocellular carcinoma patients with portal vein tumor thrombus.

6th Annual Conference of Indian Brachytherapy Society 2016 (IBSCON 2016) Proceedings

PurposeTo report the incidence, severity, and time of onset of late toxicities in patients of endometrial adenocarcinoma (EA) treated with external beam radiotherapy (EBRT) + brachytherapy (BT), or vaginal brachytherapy (VBT) alone.Material and methodsArchives of a single institution from 2008-2015 were studied. The indications for EBRT and VBT were based on standard recommendations. EBRT was planned to 50 Gy/25 fractions/5 weeks/3DCRT with 4-field ‘box’ technique on a dual energy linear accelerator. VBT was planned using appropriate vaginal cylinder treating upper half of vaginal cuff, prescribed 5 mm from vaginal surface using Ir-192 micro-Selectron to doses of 4 Gy x 4 fractions/4 days or 6 Gy x 5 fractions/ 7 days with or without EBRT, respectively. Intra-cavitary BT (ICBT) was prescribed to point A to 7 Gy x 3 fractions once weekly. Survival was calculated from Kaplan-Meier curves, and toxicity was recorded using CTCAE V3.ResultsOf 120 patients registered, 19 were excluded due to inadequate follow-up. Among the 63 patients who received RT, 18 received VBT alone and 40 received adjuvant EBRT + VBT. Five patients received definitive EBRT + ICBT, all of whom are disease free with median follow-up of 36.5 (range: 18-76) months. With median follow-up of 30 (range: 0.8-81) months, median DFS and OS were 79.2% and 75.7%, respectively in the adjuvant RT setting. Cystitis, proctitis, and enteritis was reported in 7% (all grade I/II), 17% (9% grade I/II and 8% grade III), and 5% (all grade I/II), respectively. All toxicities were seen in the EBRT arm. EBRT resulted in significantly higher proctitis than VBT alone (p = 0.02). The median time to cystitis, proctitis, and enteritis were 27, 17, and 28 months, respectively.ConclusionWith the use of 3D-CRT in endometrial adenocarcinoma, late toxicity rates appear low and mild, however EBRT leads to significantly higher proctitis than VBT alone.

Patient and Clinician Reported Acute Toxicity During Preoperative Chemoradiation for Locally Advanced Rectal Cancer

Preoperative pelvic radiation therapy (RT) with concurrent 5-Fluorouracil (FU)-based chemotherapy is the standard of care for patients with locally advanced rectal cancer. Pelvic RT is associated with significant acute toxicities that can adversely impact a patient’s quality of life. As opposed to 3D conformal RT (3DCRT), intensity modulated RT (IMRT) allows for more focal dose delivery, thus sparing normal tissues. We compared clinician reported acute toxicity profiles between patients treated with IMRT and 3DCRT and described patient reported outcomes (PROs) for IMRT patients. We retrospectively reviewed records of 335 consecutive rectal cancer patients treated with preoperative pelvic RT at our institution from 2007–2014. Clinical information, including weekly acute toxicity graded according to the CTCAE v3.0, was collected. Weekly PROs using a 7 or 14-item questionnaire based on the Bowel Problems Scale, and NCI PRO-CTCAE were also collected for 150 patients treated with IMRT from 2009–2014. Symptom frequency, severity and interference with daily activities were reported on a 5-point Likert-type scale between 1-“not at all” and 5-“very frequently” A clinically meaningful PRO score was defined as ≥3. Fisher exact test was used to test for statistical differences. The median age was 56 years (range, 22–93) and 202 (60%) patients were male. The majority of patients had clinical stage T3 (79%) and N+ (79%) disease. Of the 335 patients, 229 (68%) were treated with IMRT and 106 (32%) with 3DCRT. All patients received concurrent 5-FU-based chemotherapy with no significant difference in the median RT dose between the two cohorts. Significantly fewer patients experienced ≥grade 2 diarrhea in the IMRT group compared to the 3DCRT group (11% vs 22%, P = .02). While no grade 3 cystitis or proctitis occurred in either groups, fewer patients experienced grade 2 cystitis in the IMRT group (5% vs 12% 3DCRT, P = .02), and there was a trend towards decreased grade 2 proctitis in the IMRT group (19% vs 28% 3DCRT, P = .06). Of the 150 IMRT patients who completed PROs, a high proportion reported PRO scores ≥3 for diarrhea (65%) and urgency (73%). About half of the patients experienced rectal pain (53%) and tenesmus (49%), with fewer complaining of abdominal cramping (42%), rectal bleeding (34%) and loss of bowel control (30%). In this large cohort of patients undergoing preoperative chemoradiation for locally advanced rectal cancer, compared to the use of 3DCRT, the use of IMRT significantly reduced lower gastrointestinal and genitourinary toxicity during treatment as measured by clinicians. Patient reported outcomes show that lower gastrointestinal toxicity is experienced frequently amongst patients treated with IMRT. Further studies are needed to determine the best method to assess the impact of IMRT on treatment related toxicities.

Three-dimensional conformal fractionated radiotherapy for spinal schwannoma with a paravertebral or an intraosseous component.

We retrospectively evaluated the efficacy of three-dimensional conformal radiotherapy (3D-CRT) for spinal schwannoma. Nine patients with spinal schwannoma were treated with 3D-CRT. All patients had a paravertebral or intraosseous component. Tumor sizes ranged from 0.8 to 8.7 cm, with a median of 3.5 cm. The prescribed dose was 50 Gy in 25 fractions at the isocenter, except for 1 patient who received 66 Gy in 33 fractions for a large sacral tumor. The follow-up period ranged from 20 to 137 months, with a median of 72 months. Tumor shrinkage within 3 mm occurred in 4 patients and tumor expansion within 3 mm occurred in 3. One tumor showed neither expansion nor shrinkage at the last follow-up. One patient experienced transient expansion by 8 mm in diameter at 12 months after the completion of radiotherapy (35-43 mm), and then the tumor size remained unchanged for 7 years. No severe late toxicity ≥ grade 3 was observed. Only 1 of 9 tumors showed transit expansion over 3 mm after 3D-CRT, and severe late radiation toxicity was not observed. Use of 3D-CRT should be considered a treatment option for spinal schwannoma.

Clinical and dosimetric predictors of acute hematologic toxicity in rectal cancer patients undergoing chemoradiotherapy

Background and purposeTo identify clinical and dosimetric factors associated with hematologic toxicity (HT) during chemoradiotherapy for rectal cancer. Materials and methodsWe analyzed 120 rectal cancer patients treated with neoadjuvant pelvic radiotherapy (PRT) with concurrent 5-fluorouracil-based chemotherapy. The coxal (ilium, ischium, and pubis) bone marrow (BM), sacral BM, and femoral BM were contoured and dose-volume parameters were extracted. Associations between cell count trend and clinical predictors were tested using repeated-measures analysis of variance (ANOVA) test. Associations between clinical variables, Vx (percentage volume receiving x Gy), and cell count ratio at nadir were tested using linear regression models. ResultsNadirs for white blood cell count (WBC), absolute neutrophil count (ANC), and platelets (PLT) occurred in the second week of PRT and the fifth week for hemoglobin and absolute lymphocyte count (ALC). Using cell count ratio, patients treated with 3DCRT had a lower WBC ratio trend during PRT compared to patients treated with IMRT (p=0.04), and patients ⩾59years of age had a lower hemoglobin ratio trend during PRT (p=0.02). Using absolute cell count, patients treated with 3DCRT had lower ANC cell count trend (p=0.03), and women had lower hemoglobin cell count trend compared to men (p=0.03). On univariate analysis, use of 3DCRT was associated with a lower WBC ratio at nadir (p=0.02). On multiple regression analysis using dosimetric variables, coxal BM V45 (p=0.03) and sacral BM V45 (p=0.03) were associated with a lower WBC and ANC ratio at nadir, respectively. ConclusionsHT trends during PRT revealed distinct patterns: WBC, ANC, and PLT cell counts reach nadirs early and recover, while hemoglobin and ALC decline steadily. Patients who were treated with 3DCRT and older patients experienced lower cell count ratio trend during PRT. Dosimetric constraints using coxal BM V45 and sacral BM V45 can be considered.