3D Conformal RT Research Articles

Current practices of craniospinal irradiation techniques in Turkey: a comprehensive dosimetric analysis

ObjectiveThis study evaluates various craniospinal irradiation (CSI) techniques used in Turkish centers to understand their advantages, disadvantages and overall effectiveness, with a focus on enhancing dose distribution.MethodsAnonymized CT scans of adult and pediatric patients, alongside target volumes and organ-at-risk (OAR) structures, were shared with 25 local radiotherapy centers. They were tasked to develop optimal treatment plans delivering 36 Gy in 20 fractions with 95% PTV coverage, while minimizing OAR exposure. The same CT data was sent to a US proton therapy center for comparison. Various planning systems and treatment techniques (3D conformal RT, IMRT, VMAT, tomotherapy) were utilized. Elekta Proknow software was used to analyze parameters, assess dose distributions, mean doses, conformity index (CI), and homogeneity index (HI) for both target volumes and OARs. Comparisons were made against proton therapy.ResultsAll techniques consistently achieved excellent PTV coverage (V95 > 98%) for both adult and pediatric patients. Tomotherapy closely approached ideal Dmean doses for all PTVs, while 3D-CRT had higher Dmean for PTV_brain. Tomotherapy excelled in CI and HI for PTVs. IMRT resulted in lower pediatric heart, kidney, parotid, and eye doses, while 3D-CRT achieved the lowest adult lung doses. Tomotherapy approached proton therapy doses for adult kidneys and thyroid, while IMRT excelled for adult heart, kidney, parotid, esophagus, and eyes.ConclusionModern radiotherapy techniques offer improved target coverage and OAR protection. However, 3D techniques are continued to be used for CSI. Notably, proton therapy stands out as the most efficient approach, closely followed by Tomotherapy in terms of achieving superior target coverage and OAR protection.

Quality Assessment Radiotherapy Planning of Breast Cancer Patients with Built-In Metal Port Implants

Purpose: To evaluate the quality of radiation planning for breast cancer patients with implants with a built-in metal port. Conduct a quantitative analysis of the quality of planning, assess the dose load on critical organs for this category of patients.Material and methods: Homogeneity and conformity indices were calculated, and dose loads in critical organs were assessed for irradiation plans using 3D conformal RT (3D CRT) technology for 23 breast cancer patients with a built-in metal port implants. Calculations were carried out both taking into account (outlining) the metal port and artifacts from it on CT images, and without taking it into account.Results: Based on the results of the analysis of the calculated values of conformity and homogeneity indices, doses in critical organs of irradiation plans for 23 patients with breast cancer, it was shown that the presence of a metal port and artifacts from it affects the nature of the dose distribution.Conclusions: When creating a 3D CRT treatment plan, it is necessary to delineate the metal port and artifacts and assign true densities.

Cardiac exposure in left-sided breast cancer patients undergoing deep inspiratory breath hold radiation therapy.

Left-sided breast cancer (BC) patients undergoing post-operative radiation therapy (PRT) may have higher risk of late cardiovascular toxicity, which may be reduced by hearth-sparing RT techniques. This study evaluated dosimetric parameters of the deep inspiration breath hold (DIBH) compared to free breathing (FB) RT. We analysed factors impacting on doses to the heart and cardiac substructures and sought anatomic factors allowing patient selection for DIBH. The study group included 67 left-sided BC patients who underwent RT after breast-conserving surgery or mastectomy. Patients treated with DIBH were trained to hold their breath. Computed tomography (CT) scans were performed in both FB and DIBH patients. Plans were generated using 3-dimensional (3D) conformal RT. The dosimetric variables were obtained from dose-volume histograms, and the anatomical variables were derived from the CT scans. The variables in the two groups were compared by t-test, the U test, and the chi-squared test. Correlation analysis was performed using Pearson's correlation coefficient. Receiver operating characteristic curves were used to analyze the efficacy of the predictors. Compared to the FB, DIBH allowed for a mean dose reduction to the heart, left anterior descending coronary artery (LAD), left ventricle (LV), and right ventricle (RV) by 30.0%, 38.7%, 39.3%, and 34.7%, respectively. DIBH markedly increased the heart height (HH), heart chest wall distance (HCWD), the mean distance between the ipsilateral lung and breast (DBIB), and decreased the heart-chest wall length (HCWL) (P<0.05). The different value of HH, DBIB, HCWL, and HCWD between DIBH and FB were 1.31, 1.95, -0.67, and 0.22 cm, respectively (all P<0.05). ΔHH was an independent predictor of the mean dose to the heart, LAD, LV, and RV, with the area under the curve values of 0.818, 0.725, 0.821, and 0.820, respectively. DIBH significantly reduced the dose to the entire heart and its substructures in left-sided BC patients undergoing post-operative RT. ΔHH predicts the mean dose to the heart and its substructures. These results may inform patient selection for DIBH.

Development and Validation of a Normal Tissue Complication Probability Model for Lymphedema After Radiation Therapy in Breast Cancer

To develop and test a multivariable normal tissue complication probability (NTCP) model predicting lymphedema in patients with breast cancer receiving radiotherapy. We retrospectively reviewed 1345 patients with breast cancer who received radiotherapy from two independent institutions. The patients were divided into a training cohort (Institution A, n=368, all treated with 3D conformal external beam RT [3DCRT] with 2Gy/fraction) and an external validation cohort (Institution B, n=977, treated either with 3DCRT or with volumetric modulated RT and either with 1.8-2.0Gy/fraction or with 2.67Gy/fraction). Axillary-lateral thoracic vessel juncture (ALTJ) was delineated. The multivariable model was generated using dosimetric and clinical parameters. The performance of the model was comprehensively validated internally and externally. During a median follow-up of 78.7 months for the entire cohort, 97 patients (7.2%) developed lymphedema. The multivariable model that took into account the number of lymph nodes dissected (LNDno), as well as the volume of the ALTJ receiving a dose ≥ 35Gy EQD2 (ALTJ V35), showed good agreement between predicted and observed results for both internal and external validation (Hosmer-Lemeshow p-value > 0.05). The area under the curve (AUC) and negative log-likelihood (NLL) values for the multivariable NTCP model were 0.89 and 0.19 in internal validation and 0.83 and 0.19 in external validation. In addition, the multivariable model performance was acceptable for hypofractionated regimens (AUC 0.70) and VMAT (AUC 0.69). LNDno and ALTJ V35 were found to be the most important factors influencing lymphedema after radiotherapy. We first developed and validated the multivariable NTCP model for the lymphedema incidence in patients with breast cancer after radiotherapy. The multivariable NTCP model showed excellent performance and robustness in predicting lymphedema in both internal and completely independent external validations. The multivariable model for lymphedema prediction was robust and reliable for different treatment modalities and fractionation regimens.

CANTO-RT: One of the Largest Prospective Multicenter Cohort of Early Breast Cancer Patients Treated with Radiotherapy including Full DICOM RT Data.

This article describes the methodology used and provides a characterization of the study population in CANTO-RT (CANcer TOxicities RadioTherapy). CANTO (NCT01993498) is a prospective clinical cohort study including patients with stage I-III BC from 26 French cancer centers. Patients matching all CANTO inclusion and exclusion criteria who received RT in one of the 10 top recruiting CANTO centers were selected. Individual full DICOM RT files were collected, pseudo-anonymized, structured and analyzed on the CANTO-RT/UNITRAD web platform. CANTO-RT included 3875 BC patients with a median follow-up of 64 months. Among the 3797 patients with unilateral RT, 3065 (80.4%) had breast-conserving surgery, and 2712 (71.5%) had sentinel node surgery. Tumor bed boost was delivered in 2658 patients (68.5%) and lymph node RT in 1356 patients (35%), including internal mammary chain in 844 patients (21.8%). Most patients (3691 (95.3%)) were treated with 3D conformal RT. Target volumes, organs at risk contours and dose/volume histograms were extracted after quality-control procedures. CANTO-RT is one of the largest early BC prospective cohorts with full individual clinical, biological, imaging and DICOM RT data available. It is a valuable resource for the identification and validation of clinical and dosimetric predictive factors of RT and multimodal treatment-related toxicities.

Radiotherapy Physics Quality Assurance and Management Practices in Less Resourced Facilities: An Initial Pilot Survey in Six Countries Followed by an Onsite Visit and Audit of Radiotherapy Centers in a Lower Middle-Income Country (LMIC)

<h3>Purpose/Objective(s)</h3> To assess physics quality assurance (PQA) and practices in less resourced RT clinics to improve the quality of care. <h3>Materials/Methods</h3> An initial survey was conducted in 2020 to thirteen select RT centers in six countries. In 2021, from the survey outcome, our team conducted onsite visits to all the RT-centers in one of the countries: one private, and two public (Public-1- and –2). Public-1 in the capital and Public-2 in a regional capital. Follow-up surveys were sent to 17 medical physicists. Questions centered on the topic of equipment, institutional practice, physics quality assurance, management, and safety practices. Qualitative and descriptive methods were used for data analysis. We accessed operational challenges using a 5-point Likert system: machine downtime, patient related issues, power outage and staffing. <h3>Results</h3> We received a 100% response rate. Six (6/17) had 1-3 years of experience and two (2/17) have over 15 years of experience. Over 80% of respondents had experience with a treatment planning system. Private and public-1 have CT simulators located in RT clinic. Breast, genitourinary, Gynecologic, H&N were the most treated diseases in all three centers. All three (3) clinics have 3D conformal RT (3D-CRT), the private and public-2 have electron treatment modalities and only public-1 have IMRT treatment available. An audit during the visit showed that no single point diode patient specific QA is done for 3D-CRT patients and none of the institutions had a functioning diode to carry out this QA process. The average daily patient workload on external beam device for each clinic was LINAC: Private = 25, public-1 = 55, public-2 = 40; Co- 60: public-1 = 45, Public-2 = 25. Public-1 and-2 lacked the equipment necessary to conform to best practices in TG-142 and 198. Public-2 reported significant challenges in the operational challenges above with values of 4.5, 3 and 2.75 and 2.25. Notably Public-1 and-2 have peer review chart rounds which are attended by clinical oncologists, medical physicists, physicians, and physics trainees. All (17/17) responded to having a system of documenting, tracking, and trending patient related safety incidents but only one (1/17) physicist reported using a voluntary incident reporting system. Although not quantifiable audits during site visits show education and training remains the most important need in operating successful local PQA and management programs. In the initial survey RT centers in lower GNIpc country there was a direct correlation between QA needs and the country index. <h3>Conclusion</h3> The initial study showed a direct correlation between QA needs and the development index of a country which has led to the first of a continent-wide survey intended to spotlight PQA practices in LIMCs, the challenges faced, lessons learned, to help understand the gaps and needs to better support their local PQA and management programs.

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.

Evaluation of Patient-Reported Outcome Differences by Radiotherapy Techniques for Bone Metastases in A Population-Based Healthcare System.

We assessed whether advanced RT techniques were associated with differences in patient-reported outcomes (PROs). Patients with bone metastases who completed the brief pain inventory (BPI) before and after RT were identified, and RT technique was categorized as simple (e.g., parallel opposed pair) or advanced (e.g., 3D-conformal RT (3DCRT), intensity-modulated RT (IMRT), or stereotactic ablative RT (SABR)). Pain response and patient-reported interference on quality of life secondary to pain was compared. A total of 1712 patients completed the BPI. From 2017–2021, the rate of advanced RT technique increased significantly (p < 0.001; 2.4%, 2.4%, 9.7%, 5.5%, 9.3%), with most advanced techniques consisting of IMRT, and only 7% of advanced techniques were SABR. Comparing simple vs. advanced technique, neither the complete pain response (12.3% vs. 11.4%; p = 0.99) nor the partial pain response (50.0% vs. 51.8%; p = 0.42) was significantly different. There was no significant patient-reported difference in pain interfering with general activity, mood, walking ability, normal work, relationships, sleep, or enjoyment of life. Given that there is increasing utilization of advanced RT techniques, there is further need for randomized trials to assess their benefits given the increased cost and inconvenience to patients.

Finding safe dose-volume constraints for re-irradiation with SBRT of patients with prostate cancer relapse: The IEO experience

The primary aim of this study is to provide preliminary indications for safe constraints of rectum and bladder in patients re-irradiated with stereotactic body RT (SBRT). Data from patients treated for prostate cancer (PCa) and intraprostatic relapse, from 1998 to 2016, were retrospectively collected. First RT course was delivered with 3D conformal RT techniques, SBRT or volumetric modulated arc therapy (VMAT). All patients underwent re-irradiation with SBRT with heavy hypofractionated schedules. Cumulative dose-volume values to organs at risk (OARs) were computed and possible correlation with developed toxicities was investigated. Twenty-six patients were included. Median age at re-irradiation was 75years, mean interval between the two RT courses was 5.6years and the median follow-up was 47.7months (13.4-114.3months). After re-irradiation, acute and late G≥2 GU toxicity events were reported in 3 (12%) and 10 (38%) patients, respectively, while late G≥2 GI events were reported in 4 (15%) patients. No acute G≥2 GI side effects were registered. Patients receiving an equivalent uniform dose of the two RT treatments<131Gy appeared to be at higher risk of progression (4-yr b-PFS: 19% vs 33%, p=0.145). Cumulative re-irradiation constraints that appear to be safe are D30% < 57.9Gy for bladder and D30% < 66.0Gy, D60% < 38.0Gy and V122.1 Gy<5% for rectum. Preliminary re-irradiation constraints for bladder and rectum have been reported. Our preliminary investigation may serve to clear some grey areas of PCa re-irradiation.

Proton Therapy for Head and Neck Cancer: Current Clinical Applications and Future Direction

Intensity-modulated radiation therapy (IMRT) using X-rays is a standard technique implemented for treating head and neck cancer (HNC). Compared to 3D conformal RT, IMRT can significantly reduce the radiation dose to surrounding normal tissues by using a highly conformal dose to the tumor. Proton therapy is a type of RT that uses positively charged particles named protons. Proton therapy has a unique energy deposit (i.e., Bragg peak) and greater biological effectiveness than that of therapy using X-rays. These inherent properties of proton therapy make the technique advantageous for HNC treatment. Recently, advanced techniques such as intensity-modulated proton therapy have further decreased the dose to normal organs with a higher conformal dose to the tumor. The usage of proton therapy for HNC is becoming widespread as the number of operational proton therapy centers has increased worldwide. This paper aims to present the current clinical evidence of proton therapy utility to HNC clinicians through a literature review. It also discusses the challenges associated with proton therapy and prospective development of the technique. Key Words: Proton therapy, Intensity-modulated proton therapy, Radiation therapy, Head and neck cancer

Provider-Level Variation in Treatment Planning of Radiation Oncology Procedures in the United States.

Variation in the use of radiation oncology procedures and technologies is poorly characterized. We sought to identify associations between the treatment planning codes used to bill for radiotherapy procedures and the demographic characteristics of the radiation oncologists submitting them. The Physician and Other Supplier Public Use File was linked to the Physician Compare database by using the physician National Provider Identifier for the year 2016. Analysis was stratified by practice setting, considering both the freestanding non-facility-based (NFB) setting and the facility-based (FB) setting. Multivariable logistic regression was used to determine provider characteristics (gender, practice rurality, and years since graduation) that predicted for the use of 3D-conformal RT (3DCRT) planning, intensity-modulated RT (IMRT) planning, and brachytherapy planning in the Medicare population. Three thousand twenty-nine physicians were linked for analysis. In both the FB and NFB settings together, male gender predicted for decreased likelihood of 3DCRT planning (OR, 0.70, 95% CI, 0.62 to 0.80, P < .001) and increased likelihood of IMRT planning (OR, 1.35, 95% CI, 1.19 to 1.54, P < .001). Brachytherapy planning was also more likely with increasing years since medical school graduation (OR, 1.03, 95% CI, 1.01 to 1.04, P < .001) in the combined FB and NFB settings. These significant associations persisted when examining the NFB and FB settings individually. In both settings overall, brachytherapy planning was more likely in male providers (OR, 1.75, 95% CI, 1.10 to 2.76, P = .02) and also more likely for providers practicing in metropolitan regions compared with those practicing in rural areas (OR, 3.01, 95% CI, 1.23 to 7.39, P = .02). Male gender predicts for utilization of IMRT planning, whereas female gender predicts for utilization of 3DCRT planning. Future research is warranted to better understand the role that provider gender and rurality play in the selection of radiation planning techniques for Medicare patients.

PO-0984: Dosimetric Analysis of External Beam Modalities for APBI: Comparing 3D-Conformal and MRGuided RT

PO-0984: Dosimetric Analysis of External Beam Modalities for APBI: Comparing 3D-Conformal and MRGuided RT

Simultaneous Integrated Boost During Postoperative Radiotherapy in Extremity Soft Tissue Sarcoma

Intensity modulated radiotherapy (IMRT) has allowed the use of simultaneous integrated boost (SIB) volumes. We compared the outcomes of extremity soft tissue sarcoma (eSTS) patients treated with postoperative RT with either a sequential or integrated boost. We retrospectively reviewed a prospectively maintained institutional database of eSTS patients. All patients underwent assessment by both a surgical and radiation oncologist and surgical resection prior to definitive treatment. The majority underwent preoperative radiation followed by surgery as that was the preferred option. When chosen, postoperative RT consisted of either a 2 phase plan with 50 Gy in 25 fractions followed by 16 Gy in 8 fraction boost (total 66 Gy in 33 fractions) to a reduced volume or a single phase delivering 56 Gy in 33 fractions to the larger volume and 66 Gy in 33 fractions (SIB) to the reduced volume. The change from 3D-conformal RT (3DCRT) to IMRT facilitated the use of SIB. Functional outcomes were collected using Toronto Extremity Salvage Score (TESS) and Musculoskeletal Society Score (MSTS). Multivariable logistic regression was used to compare major wound healing complications (MWC) between the two groups. Cumulative incidence of local recurrence considering death as a competing risk was calculated. T-test was used to compare functional outcomes at each follow up time between the groups. Between January 2001 and December 2017, 112 patients were treated with surgery and RT of whom 104 were treated with post-operative radiation for eSTS excluding patients with angiosarcoma and desmoid tumor. Median age of patients was 64 years (range 17-95). Median tumor size was 9 cm, 61% had high grade tumor, 32% had upper and 68% had lower eSTS. The margin status was negative in 66% and positive in 35%. The median follow-up was 45 months (range 3-194 months). There was no significant difference in MWC between the SIB group (18%) and the sequential boost group (16%) adjusting for lower vs upper extremities and tumor size, OR (95%CI) was 1.23 (0.39, 3.86), p = 0.72. The 5-year cumulative incidence of local recurrence was 3.6% and 2.2% for the sequential and SIB groups, respectively, p = 0.35. For the entire group the 5-year local recurrence (LR) was 3.4% (0-7.3), 5-yr metastasis-free rate was: 64.3% (55.-73.8) and 5-year OS: 68.7% (60.0-78.8). There was no difference in the functional outcome scores using TESS, MSTS87. Postoperative RT in eSTS resulted in excellent local control rates. No differences were found in local control and functional outcomes between sequential or simultaneous boost techniques, although the analysis was limited by the relatively small sample size.

Radiation Therapy in the Hispanic Breast Cancer Population: An Analysis of Patient Demographics and the Impact of Insurance Status on Rates of Breast Conserving Radiation Therapy.

Disparities in minority healthcare include lower rates of insurance coverage and increased morbidity and mortality from cancer. We sought to evaluate the demographics of our Hispanic breast cancer population and evaluate the impact of insurance status on rates of breast conserving radiation therapy (BCT) including whole breast radiation (WBRT) and accelerated partial breast irradiation (APBI) versus postmastectomy radiation therapy (PMRT). We performed a retrospective review of 120 women with invasive and non-invasive breast cancer receiving curative RT between the dates of January 2017 through June 2019. Women identifying as Hispanic and all women from Latin America were included. BCT included WBRT with 3D-conformal RT (3D-CRT) and APBI with either 1. 3D-CRT or 2. HDR 192Ir brachytherapy interstitial catheters or surface applicators. We defined insurance status as 1. Insured, 2. Medicaid and 3. Non-insured. Additional patient demographics including age, BMI, country of birth, and anatomical stage were reviewed. Multivariable logistic regression model was used to evaluate odds ratios for primary outcome of WBRT/APBI as a BCT event vs. PMRT. 70 Hispanic women were identified for analysis. Median age, insurance status and cancer stage are listed (Table 1). The median BMI was 29.7 (22.0, 45.3) and median age was 58.5 (33.0, 81.0). The median BMI was non-significant but slightly lower in PMRT group (29.7 vs. 30, p-value = 0.82). Multivariable model was constituted with variable: age, BMI, primary insurance, anatomic stage, and country/region of birth (USA, Caribbean, and South/Central America). There were 58 BCT events (49 WBRT and 9 APBI) which explains enough power to construction of multivariable model. In a multivariable model, the insured subjects had 17.5 times higher odds of opting for WBRT/APBI BCT [OR (95% CI) = 17.53 (1.69, 432.0)] compared to non-insured subjects which was statistically significant (p = 0.036). This association was significant [OR (95% CI) = 6.36 (1.44, 34.37), p = 0.019] in a single variable model with more than 6 times higher odds. All other associations in the multivariable model were not statistically significant. Hispanic women comprise the majority of breast cancer patients treated at our community hospital with 83% receiving BCT versus PMRT. Insured status was a significant predictor of BCT with the insured population having an almost 18-fold higher rate of receiving WBRT or APBI than the non- insured population (OR = 17.53). Although this is a single institution study and limited by a small PMRT sample size, this health care disparity warrants further investigation to better understand access to care and barriers to BCT in the Hispanic population.Tabled 1Abstract 2925; TableWBRT/APBI n = 58PMRT n = 12All n = 70Age59.553.558.5Insured35338Medicaid12315Non-insured11617Stage 010010Stage I27027Stage II181028Stage III325 Open table in a new tab

Prospective trial of adjuvant therapy after radical cystectomy for locally advanced bladder cancer: Analysis of the squamous cell carcinoma subgroup.

524 Background: The role of adjuvant therapy after radical cystectomy (RC) is not well-defined for squamous cell carcinoma (SqCC) of the bladder. Several studies suggest limited efficacy for chemo while adjuvant RT improved disease-free survival (DFS) vs. observation in a previous trial. In this study, we report a post-hoc subgroup analysis of SqCC to compare adjuvant therapies. We hypothesized that adjuvant RT would improve DFS vs. chemo for locally advanced bladder cancer (LABC) (≥pT3N0-N+). Methods: A randomized phase III trial was opened to compare adjuvant RT vs. sandwich chemo+RT after RC for LABC at the NCI in Cairo. A 3rd arm, adjuvant chemo, was added later. Bladder cancer patients ≤70 y/o with ≥1 of the following (pT3b/pT4a, grade 3, or pN+) with negative margins after RC were eligible. RT was delivered to the pelvis with 3D conformal RT (45Gy in 1.5Gy BID). Chemo+RT included 2 cycles of gemcitabine/cisplatin before &amp; after RT. Chemo alone included gem/cis x 4. Primary &amp; secondary endpoints were DFS and overall survival (OS). Results: 198 patients were enrolled. 82 (41%) had SqCC &amp; 77 had ≥pT3N0-N+ disease and were analyzed (34 RT, 27 chemo+RT, &amp; 16 chemo). Median age was 53. Median F/U was 20 months (1-127 months). The RT vs chemo arms were well-balanced except for number of nodes removed (mean 12 vs. 9, p=0.05). On univariable analysis, RT was not significantly associated with DFS [HR 0.56 (95%CI 0.26-1.21), p=0.14]. On multivariable analysis, only pN+ was significant. 2-yr DFS was 60% for RT &amp; 43% for chemo (log-rank p=0.13). OS was improved with RT (2-yr OS 71% vs. 43%, p=0.04). There was one death during treatment (chemo-related). There was no significant difference in DFS or OS for RT vs. chemo+RT with 2-yr DFS of 59% &amp; 55% (p=0.65) &amp; 2-yr OS of 67% &amp; 74% (p=0.16). Conclusions: On post-hoc analysis, RT for locally advanced bladder SqCC was associated with significantly improved OS vs. adjuvant chemo. We hypothesize that the inferior OS with chemo was due to increased toxicity &amp; limited efficacy. There was no difference in outcomes for RT vs. chemo+RT. Adjuvant RT should be a standard option for ≥pT3 SqCC of the bladder after RC. Alternative chemo agents for SqCC should be explored. Clinical trial information: NCT01734798.

Randomized trial of adjuvant chemotherapy versus adjuvant radiation therapy for locally advanced bladder cancer after radical cystectomy.

4507 Background: Some chemotherapy-naïve patients with locally advanced bladder cancer (LABC) after radical cystectomy (RC) are sufficiently de-conditioned that they are not candidates for adjuvant chemotherapy or decline it, even though such treatment may be warranted. There is no clear alternative adjuvant therapy for these patients, who are usually observed. In this study, we compare post-op radiotherapy (PORT) vs. adjuvant chemotherapy in a randomized clinical trial. We hypothesized that PORT can achieve comparable disease-free survival (DFS). Methods: A randomized phase III trial was opened to compare PORT vs. sequential chemo+PORT after RC for LABC &amp; accrued from 2002–2008 at the NCI in Cairo. In 2007, a third arm comparing adjuvant chemo was added. Herein, we report the results of PORT vs. adjuvant chemo. Patients ≤70 y/o with ≥1 of the following factors (≥pT3b/T4a, grade 3, or positive nodes) with negative margins after RC + pelvic node dissection were eligible. Routine follow-up &amp; pelvic CT q6 months were performed. PORT included 3D conformal pelvic RT (45Gy/1.5Gy BID). Chemo included gemcitabine/cisplatin x 4. Post-hoc non-inferiority exploratory analysis was performed. Results: The PORT arm accrued 78; the chemo arm accrued 45. 51% had urothelial carcinoma; 49% had squamous cell carcinoma/other. The two arms were well-balanced except for gender (p = 0.06). Two-year outcomes &amp; overall adjusted hazard ratios (HR) for PORT vs. chemo alone were 54% vs. 47% (HR 0.65(95%CI 0.35-1.19, p = 0.16) for DFS; 92% vs. 69% (HR 0.28(95%CI 0.10-0.82), p = 0.02 for LRFS; 75% vs. 79% (HR 2.39(95%CI 0.94-6.09), p = 0.07) for DMFS; 61% vs. 60% (HR 0.94(95%CI 0.52-1.69), p = 0.83) for OS. Late grade ≥3 GI toxicity was observed in 6 PORT patients (8%) &amp; 1 chemo patient (2%). Based on our data, there is a greater than 90% probability that the true difference in 2 yr DFS is less than 10%, the pre-specified non-inferiority margin. Conclusions: This randomized study demonstrates superior local control with PORT vs. adjuvant chemo with no significant differences in DFS, DMFS or OS. Results suggest that PORT could be an option for patients with LABC after RC who are medically unfit for adjuvant chemo or who decline it. Clinical trial information: NCT01734798.

Effect of early salvage radiotherapy at PSA < 0.5 ng/ml and impact of post-SRT PSA nadir in post-prostatectomy recurrent prostate cancer.

For patients with recurrent prostate cancer after radical prostatectomy (RP), salvage radiotherapy (SRT) offers a second chance of cure. European guidelines (EAU) recommend SRT at a PSA < 0.5 ng/ml. We analyze the efficacy of SRT given according to this recommendation and investigate the predictive power of the post-SRT PSA nadir. Between 1998 and 2013, 301 patients of two university hospitals received SRT at a PSA < 0.5 ng/ml (median 0.192 ng/ml, IQR 0.110-0.300). Patients, who previously received androgen deprivation therapy, were excluded. All patients had 3D-conformal RT or intensity-modulated radiotherapy (IMRT, n = 59) (median 66.6 Gy). The median follow-up was 5.9 years. Progression and overall survival were the endpoints. After SRT, 252 patients re-achieved an undetectable PSA. In univariate analysis, pre-RP PSA ≥ 10 ng/ml, pT3-4, Gleason score (GS) 7-10 or 8-10, negative surgical margins, post-RP PSA ≥ 0.1 ng/ml, pre-SRT PSA ≥ 0.2 ng/ml and post-SRT PSA nadir ≥ 0.1 ng/ml correlated unfavorably with post-SRT progression. In a multivariable Cox model, pT3-4, GS 7-10, negative margins and a pre-SRT PSA ≥ 0.2 ng/ml were significant risk factors. If the post-SRT PSA was added to the analysis, it dominated the outcome (HR = 9.00). Of the patients with a pre-SRT PSA < 0.2 ng/ml, only 9% failed re-achieving an undetectable PSA. Overall survival in these patients was 98% after 5.9 years compared to 91% in patients with higher pre-SRT PSA (Logrank p = 0.004). SRT at a PSA < 0.2 ng/ml correlates significantly with achieving a post-SRT undetectable PSA (<0.1 ng/ml) and subsequently with improved freedom from progression. Given these overall favorable outcomes, whether additional androgen deprivation therapy is required for these men requires further study.

The Relationship of Mean Heart Dose and Cardiac Substructure Dose over Evolving Radiation Techniques in Mediastinal Lymphoma

Our understanding of the relationship between cardiac morbidity and mean heart dose among survivors of mediastinal lymphoma (mHL) dates back to the use of standard large-field 2D techniques. Over time, RT treatment in mHL has evolved with smaller, more personalized radiation fields and more conformal techniques, like 3D conformal RT (3D), intensity-modulated RT (IMRT), and proton therapy (PT). We investigated the relationship between mean heart dose and cardiac substructures across treatment fields and delivery techniques. We retrospectively developed IFRT (n=37) plans among selected patients with mHL treated with involved-site radiation therapy (ISRT) between 2008 and 2017. Doses to the cardiac substructures were exported to a dosimetric database of ISRT plans for mHL, including 3D (n=25), IMRT (n=28), and PT (n=36). The structures included the heart, left anterior descending artery (LAD), mitral valve (MV), tricuspid valve (TV), aortic valve (AV), left and right ventricles (LV, RV), and left and right atriam (LA, RAPlans were scaled to a prescription dose of 30 Gy and the mean heart dose was evaluated for correlation (R2) and slope (beta) of the relationship with mean dose to the cardiac substructures. The table reports the correlation coefficient (R2) and slope for the relationships between mean heart dose and mean cardiac substructure dose, demonstrating less correlation with increasingly conformal delivery. A strong correlation (R2≥70%) was seen for IFRT with RV, LV, and LAD; for 3D with RV and LV; and for IMRT with RV and LV. No strong correlation was observed for PT. When evaluating the slope (beta) for a relationship between mean heart dose and mean LAD dose, the slope was steepest for IFRT (1.86) and PT (1.69) compared to IMRT (1.36) and 3D (1.14), suggesting that a lower mean heart dose can be associated in some instances with a higher mean LAD dose with IFRT and PT compared to IMRT or 3D RT. For the LV, the slope was steepest for IFRT (2.07) followed by 3D (1.25), IMRT (1.17), and then PT (0.98). The relationship between mean heart dose and mean substructure dose changes with increasingly conformal techniques. Calculating mean heart dose as a surrogate for cardiac risk is no longer sufficient. Contouring the cardiac substructures, especially the LAD and LV, is important in understanding the late cardiac risks in the modern era of RT.Abstract 176; TableIFRT3DCRTIMRTPROTONSStructureRhoBETARhoBETARhoBETARhoBETAName(R2)(Slope)(R2)(Slope)(R2)(Slope)(R2)(Slope)Aortic Valve6%0.077%0.1035%0.7143%1.47Left Atrium48%0.2965%0.5453%0.8444%1.41Right Atrium11%0.1034%0.9236%0.8726%0.85Left Ant. Desc. art76%1.8662%1.1460%1.3652%1.69Mitral Valve50%0.7252%0.6138%0.8237%1.34Tricuspid Valve5%0.0850%1.2243%0.9616%0.51Left Ventricle95%2.0772%1.2574%1.1761%0.98Right Ventricle80%0.9085%1.1381%1.0937%0.79 Open table in a new tab

Dosimetric Analysis of Rectum and Mesorectum in 3D Conformal RT and IMRT for Intact Cervical Cancer

Dosimetric Analysis of Rectum and Mesorectum in 3D Conformal RT and IMRT for Intact Cervical Cancer

Predictors of Radiation Esophagitis in Locally Advanced Non-Small Cell Lung Cancer with Modern Radiation Therapy Planning

Radiation esophagitis (RE) is major side effect of concurrent chemoradiation (cCRT) for locally advanced non-small cell lung cancer (NSCLC). Advances in radiation technology allow for better esophageal sparing, potentially affording opportunities to reduce RE without compromising outcomes. Existing studies on RE largely do not include patients treated using intensity modulated radiation therapy (IMRT). In this study, we aimed to determine RE frequency and predictors with modern radiation planning. We retrospectively analyzed 594 NSCLC patients treated with definitive intent with cCRT using 3D-conformal RT (3D-CRT) or IMRT at one institution from 2001-2014. A mean esophageal dose constraint of 34 Gy was used in most cases. RE events were graded with the Radiation Therapy Oncology Group (RTOG) system. Predictors of RTOG grade ≥3 RE were analyzed with multivariable logistic regression using backward selection. Overall survival (OS) and progression free survival (PFS) were calculated with the Kaplan-Meier method. Median follow-up was 22.8 months (mo), median OS was 25.2 mo, and median PFS was 10.8 mo. Median age was 65.2 years and 49.8% of patients were male. At presentation, 8.4% were Stage II, 55.9% Stage IIIA, and 35.7% Stage IIIB. Adenocarcinoma made up 46.0% of cases, squamous cell carcinoma 30.0%, and NSCLC-NOS 24.1%. 3D-CRT was used in 75.1% of cases, and IMRT in 24.9%. Median prescribed dose was 66 Gy (range, 36-74 Gy) and median dose per fraction was 2 Gy (range, 1.8-3 Gy). Median maximum and mean esophageal doses were 64.7 Gy (range, 0.9-78.8 Gy) and 24.0 Gy (range, 0.4-56.8 Gy), respectively. Mean esophageal dose was >34 Gy in 95 (16.0%) of patients. Median esophageal V45, V55, and V60 were 28.7% (range, 0-82.7%), 17.0% (range, 0-73.7%), and 8.4% (range, 0-66.8%), respectively, and these values were higher in patients treated with IMRT (Table 1). Grade ≥3 RE was observed in 113 (19%) patients. On multivariable analysis, NSCLC-NOS histology (OR 2.08, 95% CI 1.23-3.53, p=0.006), IMRT (OR 0.36, 95% CI 0.20-0.63, p<0.001), and mean esophageal dose per Gy (OR 1.10, 95% CI 1.07-1.13, p<0.001) were associated with grade ≥3 RE.Abstract TU_26_3574; Table 13D-CRT and IMRT dose-volume metrics3D-CRT (n=446)IMRT (n=148)p-valuePrescribed dose, Gy (median, range)66 (36-74)66 (40-72)0.65Maximum esophageal dose, Gy63.2 (0.9-78.8)66.9 (7.5-77.5)0.0001Mean esophageal dose, Gy22.7 (0.4-56.8)27.5 (1.6-55.4)<0.0001Esophageal V45, %28.1 (0-77.8)33.2 (0-82.7)0.0002Esophageal V55, %16.0 (0-71.2)21.0 (0-73.7)0.0005Esophageal V60, %5.8 (0-66.8)16.0 (0-66.6)0.0003 Open table in a new tab Mean esophageal dose was the strongest dosimetric predictor of grade ≥3 RE. Even after controlling for higher mean esophageal dose, IMRT was associated with lower RE risk. This suggests that different dose-volume constraints may be important in 3D-CRT and IMRT plans.