3D Conformal Radiotherapy Research Articles

Field-in-field breast planning for a jawless, double-stack MLC LINAC using flattening-filter-free beams.

BackgroundThis study intends to develop an efficient field‐in‐field (FiF) planning technique with the Eclipse treatment planning system (TPS) to determine the feasibility of using the Halcyon treatment delivery system for 3D treatment of breast cancer.MethodsTen treatment plans were prepared on the Halcyon treatment planning system and compared to the same patients’ clinically delivered TrueBeam plans which used flattened 6 MV and 10 MV beams. Patients selected for this study were treated via simple, tangential breast irradiation and did not receive radiotherapy of the supraclavicular or internal mammary lymph nodes. Planning target volumes (PTV) volumes ranged from 519 cc to 1211 cc with a mean target volume of 877 cc. Several planning techniques involving collimator, gantry rotation, and number of FiF segments were investigated as well as the use of the dynamically flattened beam (DFB) — a predefined MLC pattern that is designed to provide a flattened beam profile at 10 cm depth on a standard water phantom. For comparison, the clinically delivered TrueBeam plans remained unaltered except for normalization of the target coverage to more readily compare the two treatment delivery techniques.ResultsUsing the physician defined PTV, normalized such that 98% of the volume was covered by 95% of the prescribed dose, the Halcyon plans were deemed clinically acceptable and comparable to the TrueBeam plans by the radiation oncologist. Resulting average global maximum doses in the test patients were identical between the TrueBeam and Halcyon plans (108% of Rx) and a mean PTV dose of 102.5% vs 101.6%, respectively.ConclusionsFrom this study a practical and efficient planning method for delivering 3D conformal breast radiotherapy using the Halcyon linear accelerator has been developed. When normalized to the clinically desired coverage, hot spots were maintained to acceptable levels and overall plan quality was comparable to plans delivered on conventional C‐arm LINACs.

Hippocampal sparing radiotherapy in adults with primary brain tumours: a comparative planning and dosimetric study using IMPT, IMRT and 3DCRT.

Abstract Introduction We assessed the feasibility of hippocampal sparing in adults with primary brain tumours using Intensity Modulated Proton Therapy (IMPT) and compared this with Intensity Modulated Radiotherapy (IMRT) and 3D-Conformal Radiotherapy (3DCRT). Methods and Materials 20 patients were identified, and each patient underwent a radiotherapy planning CT scan and 2 MRI scans. A pre-operative diagnostic MRI scan was fused with the planning CT and used for target delineation and a dedicated 3T MRI scan at the time of planning was fused with the CT for hippocampus delineation. 3 hippocampal sparing plans were generated for each patient with specific prescriptions (54Gy/30 fractions, 60Gy/30 fractions and 59.4Gy/33 fractions) using IMPT, IMRT and 3DCRT. Hippocampal sparing was defined as median dose to contralateral hippocampus ≤25Gy without compromising target coverage and organ at risk dose constraints. Results Hippocampal sparing was achieved in 19 patients (95%) with IMPT, 16 patients (80%) with IMRT and 13 patients (65%) with 3DCRT. The largest median hippocampal dose reduction was seen with IMPT, with a mean median hippocampal dose of 4.8Gy (range: 0.0Gy-24.9Gy), 14.6Gy (range: 1.9Gy-21.7Gy), and 16.2Gy (range: 2.3Gy-25.0Gy) for IMPT, IMRT and 3DCRT respectively. Hippocampal sparing IMPT failed in one case with the largest tumour volume (650cc) where 2/3 of the hippocampus overlapped the target volume. Conclusion IMPT as compared to IMRT and 3DCRT plans showed a trend towards significant and effective hippocampal sparing in adult patients with primary brain tumours. We are currently evaluating this in a larger patient cohort and comparing IMPT with VMAT.

Risk of Pelvic Fracture With Radiation Therapy in Older Patients

Older patients undergoing radiation therapy (RT) for pelvic malignancies are at increased risk for pelvic fracture, which is associated with significant morbidity and mortality. RT techniques such as brachytherapy or intensity modulated RT (IMRT) allow for more conformal dose distributions, but it is not known whether the risk for pelvic fracture varies by RT modality. This observational cohort study involved 28,354 patients ≥65 years old, treated with RT for pelvic malignancies. We evaluated the relative risk of pelvic fracture by type of RT when accounting for baseline factors. To test for nonspecific effects, we also evaluated risk of nonpelvic fractures in the same population. The 5-year incidence of pelvic fractures was 12.7% (95% confidence interval [CI], 11.6%-13.8%), 11.8% (10.8%-12.8%), and 3.7% (3.4%-4.0%) for patients with gastrointestinal, gynecologic, and prostate cancer, respectively. On multivariable analysis, being treated with IMRT (hazard ratio, 0.85; 95% CI, 0.73-0.99) or brachytherapy therapy alone (hazard ratio, 0.43; 95% CI, 0.34-0.54) was associated with a reduced hazard for pelvic fractures compared with 3D conformal radiation therapy in female patients. In contrast, there was no association with RT modality and the hazard for nonpelvic fractures among females. There was no significant association between pelvic fractures and IMRT or brachytherapy for male patients. White race, advanced age, and higher comorbidity were associated with an increased hazard for pelvic fracture. IMRT and brachytherapy were associated with a reduced risk of pelvic fractures in older women undergoing RT for pelvic malignancies. Pelvic insufficiency fracture risk should be considered when treating with pelvic RT.

Conformal hypofractionated radiotherapy for dogs with large adrenal tumours

Adrenalectomy has been recognised as the treatment of choice for adrenal tumours. However, excision of large tumours with or without vena caval tumour thrombi is difficult. The purpose of this...

219P - Pneumonitis and fibrosis after breast cancer radiation

BackgroundBreast cancer(BC) radiation therapy(RT) reduce local recurrence, BC mortality and improves overall survival, but may induce lung damage ranging from radiological changes only to respiratory failure. Lung toxicity may present as radiation pneumonitis (RP) 3-6 months after treatment and radiation fibrosis (RF) after 6-12 months. The aim of the study is to describe the occurrence of RP and RT after conventional RT and examine their potential predictors. Methods250 patients were entered in a prospective cohort study from February 2007 to October2008. All patients received standard postoperative 3D conformal radiation therapy (2Gy x 25) for BC. Pulmonary High Resolution Computer Tomography and clinical examinations were performed before RT and 3, 6 and 12 months after radiation treatment. Smoking habits were reported by patients. Estimated lung dosevolums (V20, V30, D25) were retrieved from the doseplan system(Oncentra). Patient- and treatment-related factors were registered by oncologists at start. Evaluation of RP and RF were performed by a radiologist according to NCÍs CTCAE (version 3.0 ). Predictors of RP and RF were evaluated by univariate and multivariable logistic regression. Patient reported outcomes were measured using EORTC QLQ-C30. ResultsThe occurence of RP 3 months after radiation therapy was 76.6% and RF 12 months after treatment was 90.5 %. 17.5% had symptomatic RP and 17.1% symptomatic RF, mainly as grade 1. In We identified correlation between mastectomy and symptomatic RP (OR=2.41 p<0.05), age and RF (OR=1.08 p<0.05) and endocrine treatment and symptomatic RF (OR=2.24 p<0.05). Smoking seems to have a protective effect against RP also demonstrated in multivareble analysis (OR=0.34 p<0.05). Before radiation treatment 30.3 % of the patients reported dyspnoea, at 3 months 42.7% and at 12 months 39.8%. Physicians registered dyspnoea by 8.4% before treatment, 14.3% at 3 months and 10.4% at 12 months. ConclusionsOur data shows that RP and RF is common the first year after BC radiation. We identified that age was associated with RP, mastectomy with symptomatic RP and endocrine therapy with symptomatic RF. Dyspnoea were more frequent reported by patients than physicians. Legal entity responsible for the studyFaculty of Medicine and Health, NTNU, Norway. FundingSentral Norway Regional Health Authority. DisclosureThe author has declared no conflicts of interest.

P03.14 New features of modern 3D conformal external radiotherapy (RT) of benign head tumors in children

Abstract BACKGROUND demonstrate the possibilities of radiation therapy (LT) in children with benign head tumors using IMRT, VMAT, IGRT techniques - high-precision modern 3D conformal radiation therapy MATERIAL AND METHODS From 1990 to 2007 for the first time in Russia, 88 children with juvenile angiofibromas were treated in Russian Scientific Center of Roentgenoradiology. The studies were carried out on the gamma-therapeutic apparatus “AGAT-P1” and on the linear accelerator “Phillips SL75” Total dose was 35–45 Gy. In 2014–2018 we treated 29 patients aged 3–17 years with benign tumors of the skull base and brain (angiofibromas, craniopharyngiomas, hemangiomas) using high-precision techniques (IMRT, VMAT, IGRT). 15 of 29 patients were repeatedly operated in various domestic and foreign clinics and were admitted to RT with the threat of bleeding, with recurrent growth of tumors, including after multiple selective angioembolization. RESULTS Up to 80% of patients had a 5-year stable remission, and the optimal total dose for radiation therapy of benign head tumors in children was scientifically substantiated. It was found that there is a high risk of continued growth after RT in children under 8 years of age, complications in 10% of patients in the coming years after RT and in 100% of those reirradiated. In all 29 cases of RT in children, we observed a positive clinical effect - stopping bleeding from the nasopharynx after 1–3 sessions of 3D conformal RT (Dose per fraction 1.8 Gy, total dose 45–54 Gy), positive clinical symptoms under the supervision of an Head and Neck surgeon. The effect of hardening and stopping the growth of tumors according to MRI data were followed up after 3 months, 6 months, 1 year. CONCLUSION The development of navigational, endosurgical and fibro-endoscopic minimally invasive technologies in the last 30 years has allowed to expand the indications for surgical methods of treatment for benign head tumors in children, which has reduced their flow to RT. However, after modern surgical interventions, 6–10% of these patients experience recurrences and bleeding, the number of which can be reduced with timely RT. New technologies in LT provide minimal impact on surrounding healthy tissues and allow wider use of RT in recurrent and difficult-to-reach benign skull base tumors in children

The Patient’s Perspective on Radiation for Rectal Cancer: Initial Expectations Versus Actual Experience

Radiation therapy (RT) serves as a key component in the multidisciplinary management of rectal cancer. How patients perceive RT, particularly in the context of their overall treatment experience, remains unclear. Consecutive patients with adenocarcinoma of the rectum treated with neo- or adjuvant chemoradiation, surgical resection, and adjuvant chemotherapy from 2009-2018 and who were without recurrence were surveyed. Patients were surveyed ≥6 months after ileostomy reversal or ≥3 months after adjuvant chemotherapy, whichever was later. The survey assessed patients’ baseline knowledge and fears of RT and asked them to compare their short- and long-term side effects with initial expectations. Patients were also asked to compare their experiences of each modality (RT, surgery, and chemotherapy). Questions were adapted from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. The response rate was 51% (40/78). The median age was 68 years (range 39-89) and 53% were female. The clinical stage distribution was 5% stage I (upstaged at surgery), 20% stage II, and 75% stage III. The majority underwent neoadjuvant (88%) chemoradiation with capecitabine (85%); 53% were treated with 3D conformal RT and 47% intensity-modulated RT (median total dose 50.4 Gy, range 45-54 Gy). Surgical resections were as follows: 65% low anterior resection, 25% abdominal perineal resection, and 10% other. The most common adjuvant chemotherapy was capecitabine/oxaliplatin (43%) for median duration of 6 cycles. Median follow-up at survey was 41 months (range 4-107 months). Before treatment, 70% of patients indicated little to no knowledge of RT, though 43% reported hearing frightening stories about RT. The most commonly top ranked fears included organ damage (26%), skin burns (14%), and inability to carry out normal daily activities (10%). Regarding short-term effects of RT, 80% reported overall effects to be less than or as expected, with urinary changes (93%), abdominal discomfort (90%), and anxiety (88%) most commonly rated as less than or as expected. Regarding long-term effects of RT, 85% reported overall effects to be less than or as expected, with pain (95%), changes to the appearance of the treated area (85%), and dissatisfaction with body image (80%) most commonly rated as less than or as expected. Of the modalities, surgery was most commonly rated as the most difficult treatment (50%) and most responsible for long-term effects (55%). RT was least commonly rated as the most difficult treatment (13%) and chemotherapy least commonly rated as most responsible for long-term effects (13%). The majority of patients indicated short- and long-term side effects of RT for rectal cancer to be better than initial expectations. In the context of trimodality therapy, patients reported RT to be the least difficult of the treatments.

Intensity-Modulated Radiation Therapy versus 3D Conformal Radiation Therapy in Patients Undergoing Regional Nodal Irradiation/Postmastectomy Radiation Therapy for Breast Cancer: Looking Beyond Dosimetric Outcomes

Prospective data and meta-analyses support the use of adjuvant regional nodal irradiation (RNI)/postmastectomy radiation therapy (PMRT) for the majority of women with axillary lymph node positive breast cancer. However, RNI increases dose to the heart and lung compared resulting in increased toxicity. Inverse-planned intensity modulated radiation therapy (IMRT) has the ability to reduce high dose to the heart/lung compared to traditional 3D conformal radiation therapy (3DCRT). Early concerns with IMRT were that it may be too conformal resulting in increased risk of local-regional failures (LRF). To date, clinical outcomes with IMRT have not been well studied in patients receiving RNI/PMRT. We have used planning target volume (PTV)-based, dose-volume analysis driven RNI/PMRT planning since 2013 using primarily 3DCRT but IMRT as needed to meet heart/lung planning objectives. We hypothesize that toxicity and LRF rates are similar between patients treated with IMRT and 3DCRT. We identified patients that received RNI/PMRT from 2013-2016. Patients received conventional fractionation (200 cGy/day) to the breast/chestwall, axillary, supraclavicular (SCV), and internal mammary chain (IMC) PTVs. We divided the cohort into 2 groups (IMRT vs. 3DCRT). We collected patient and disease characteristics, acute toxicity, LRF, and distant metastases (DM) events. Differences in characteristics were evaluated with the t-test or Chi-square test. The primary endpoint was the cumulative incidence of LRF as a first failure. We also evaluated the cumulative incidence of DM. We included 241 patients (69 IMRT, 172 3DCRT): 60% had stage III disease; 60% (ER+ or PR+)/HER2-; 20% triple-negative; 20% HER2+. IMRT group had higher rates of left-sided (65% vs. 47%, p=0.009) and grade 3 (58% vs. 43%, p=0.04) disease. The IMCs were irradiated in 97%. Treatment was well tolerated: grade 3 dermatitis 6% in each group with no other grade 3 toxicities. Grade 2 pneumonitis occurred in 2 (0.83%), both 3DCRT. Median follow-up is 3.5 years. There were 5 LRF events (2 IMRT, 3 3DCRT): 2 patients with isolated LRF (iLRF) and 3 patients with simultaneous LRF+DM resulting in 4-year LRF=2.1% (4.1% IMRT vs. 1.4% 3DCRT, p=0.55) and 4-yr iLRF=1.1% (1.5% vs. 0.8%, p=0.43). The iLRF (1 IMRT, 1 3DCRT) both occurred in the SCV region. The other LRF+DM event in the IMRT group was a chestwall/axillary/IMC recurrence post-mastectomy. The additional 2 LRF+DM events in the 3DCRT group included: ipsilateral SCV and level V nodes post-lumpectomy; and a lumpectomy bed recurrence. Most failures were DM: 4-year rate=15% (21.0% IMRT vs. 13.2% 3DCRT, p=0.58). In this modern cohort of patients receiving RNI/PMRT with a PTV-based approach, we saw rare high-grade toxicity, and we found no difference in LRF and DM rates between IMRT and 3DCRT patients. These data should provide reassurance that IMRT does not compromise disease outcomes and that IMRT can safely be used when needed to meet normal tissue constraints.

Changing Practice Patterns in the Radiation Treatment Delivery for Locally Advanced Lung Cancer: Results from a Statewide Consortium

In 2014, the RTOG 0617 trial defined the standard radiation therapy (RT) dose as 60 Gy with concurrent chemotherapy in locally advanced non-small cell lung cancer (LA-NSCLC) patients. Further analyses of the study showed a decrease in grade 3 pneumonitis with static intensity modulated radiation therapy (sIMRT). Radiation treatment techniques used in routine clinical practice have evolved from 3D conformal radiation therapy (3DCRT) to sIMRT and more recently to rotational IMRT (rIMRT). However, the uptake of lower lung tumor RT dose recommendations and RT treatment techniques used in the “real world” setting is not known. The purpose of this study was to evaluate patterns of practice of both radiation dose and type of radiation technique used in a statewide radiation oncology consortium. From 2012 to 2018, 2741 patients with lung cancer treated with curative intent RT at 24 institutions participating in a statewide Radiation Oncology Quality Consortium were enrolled. Patients with small cell lung cancer, previous surgical resection, and patients who did not complete treatment were excluded. Furthermore, for RT dose analyses, outliers of RT doses (<45 Gy and >100 Gy) were excluded. Patients lacking DICOM information regarding treatment plans were excluded for the RT technique analyses. Changes in prescription doses and treatment techniques over time were evaluated. Trends over time in academic (n=4) vs. non-academic centers (n=20) were also analyzed. Academic centers were defined as those with a medical residency training program. Sample t-tests were used to compare means. 1134 patients were analyzed for RT dose analysis, while 1087 patients were evaluated for the RT treatment technique. The mean prescription RT dose delivered to tumor decreased from 63 Gy to 60 Gy (p<0.001) over the 6-year time period. In the earlier years of the data collection (2012-2013), >50% of the cases were treated with 3DCRT and rIMRT was used in ≤5%. However, by 2018, the rate of rIMRT increased to 56.9% (p<0.0001). See Table below. Similar practice patterns were seen in academic and non-academic centers for both RT dose and treatment technique analyses. In this large prospective “real world” study from a statewide consortium of practicing radiation oncologists, prescription mean RT dose used to treat LA-NSCLC has decreased to 60 Gy as per evidence-based guidelines. The primary treatment technique of delivering RT in LA-NSCLC has also changed in this interval. More than half of LA-NSCLC patients are now receiving rIMRT. The clinical implications of potential increases in low dose volumes (e.g., Lung and Heart V5) resulting from rIMRT will have to be evaluated going forward, especially in the changing systemic therapy paradigm that includes immunotherapy.Abstract 3120; Table 1Year3DCRTsIMRTrIMRT201263.5%34.6%1.9%201355.1%40.4%4.5%201444.8%38.1%17.2%201540.2%33.1%26.7%201619.0%31.4%49.6%201721.9%25.1%53%201821.8%21.3%56.9% Open table in a new tab

Analysis of Chronic Renal Failure Following Radiotherapy for Gastric/Duodenal Mucosa-associated Lymphoid Tissue Lymphoma at a Single Institution

Only few studies have analyzed chronic radiotherapy (RT)-associated renal failure owing to its long latency period. This study was aimed at evaluating the relationship between renal failure after RT for gastric/duodenal mucosa-associated lymphoid tissue (MALT) lymphoma and the dose–volume histogram (DVH) of the kidneys. We analyzed the data of 37 patients (median age, 62 [range, 38–81] years) diagnosed with gastric/duodenal MALT lymphoma treated with RT alone between February 2002 and October 2017. Selection criteria included patients treated with 3D conformal RT, with analyzable DVH data, and followed up for at least 6 months. Patients with decreased renal function before RT were excluded. Chronic renal failure was defined as continuous elevation of serum creatinine levels. Creatinine increases were evaluated using the Common Terminology Criteria for Adverse Events version 5.0. Mean bilateral kidney dose, DVH Vx (Vx, percentage bilateral kidney volume receiving ≥x Gy), and patients’ baseline clinical characteristics were analyzed. The Mann–Whitney U-test as well as univariate and multivariate logistic regression analyses were used to evaluate the associations between dosimetric parameters and increases in serum creatinine levels. Statistical significance was defined as p-value < 0.05. Regarding the primary disease, 33 patients had gastric disease, 2 had duodenal disease, and 2 had gastroduodenal disease. The median RT dose was 30 (range, 24–44.8) Gy in 15 fractions. At the median follow-up period of 65 (range, 9–203) months, 13 of the 37 (35.1%) patients experienced grade 1 increased creatinine levels and 4 others (10.8%) experienced grade 2 toxicity. No patients experienced ≥grade 3 toxicity. Various Vx (V5, 10, 15, and 25) and mean bilateral kidney doses were significantly associated with the probability of grade 1 increased creatinine levels. The most significant difference was observed for V10 (p = 0.002). The rates of renal toxicity were higher in patients with V10 ≥ 45% than in those with V10 < 45% (64.3% vs. 17.4%, respectively; p < 0.05). Increased bilateral kidney V10 was associated with chronic renal failure in patients with MALT lymphoma undergoing RT. Chronic renal failure was observed over an extended follow-up period after RT; hence, continuous follow-up was needed.

Hemoglobin Level during Radiotherapy Predicts Survival Outcomes after Radiochemotherapy for Stage III Non-Small Cell Lung Cancer

Low hemoglobin (Hgb) levels have been linked with poor prognosis in various malignancies including non-small cell lung cancer (NSCLC). Here we tested the hypothesis that low Hgb levels during radiochemotherapy for stage III NSCLC are associated with lower rates of overall survival (OS), disease-free survival (DFS), and distant metastasis(DM). We retrospectively reviewed Hgb levels before and during definitive radiochemotherapy (radiation dose ≥60 Gy) in 189 patients with inoperable stage III NSCLC. Seventy-nine (42%) patients were treated with 3D conformal radiotherapy (3DCRT), 85 (45%) with intensity-modulated radiotherapy (IMRT), and 24 (13%) with passive scattering proton therapy (PSPT), 1 patient received PSPT and IMRT sequentially. Eighty-one patients (43%) received induction chemotherapy. We calculated Hgb means before and during treatment and analyzed the changes in these values. Potential associations between mean Hgb levels during treatment and rates of OS, DM, and DFS were analyzed with Cox proportional hazards models. Mean Hgb levels before and during treatment for all patients were 13.2 g/dL (range 8.2−17.4) and 11.5 g/dL (range 8.6−14.7). Hgb decreased in most patients during treatment (mean difference 2.1 g/dL [range 0.5−6.9]). The median follow-up time was 21.3 months (range 2.8–121.4). In univariate analyses, mean Hgb levels were found to be associated with OS (hazard ratio [HR] 0.856, 95% confidence interval [CI] 0.750–0.977, P=0.021), DFS (HR 0.818, 95% CI 0.711–0.941,P=0.005), and DM (HR 0.786, 95% CI 0.668–0.924, P=0.004). Gross tumor volume (GTV) and tumor histology were also associated with survival outcomes and applied in multivariate analysis. Mean Hgb level was still significantly associated with OS (HR 0.871, 95% CI 0.763–0.994, P=0.041), DFS (HR 0.853, 95% CI 0.739–0.985,P=0.03), and DM (HR 0.837, 95% CI 0.709–0.988, P=0.035) after adjustment for GTV and histology. Hgb decreased during radiotherapy. Low Hgb levels during treatment predicted poorer OS, DFS, and DM in patients with stage III NSCLC. Monitoring Hgb levels during radiotherapy in large multi-center studies is recommended to validate the role of Hgb and to select threshold values.

Lung Density Changes Following SBRT: Association with Lung Dose and Clinical Pneumonitis

Radiation pneumonitis is an inflammation of the lungs that can develop following radiation therapy, the cause of which is not fully understood. The hypothesis of this study is that radiation induced lung changes are associated with radiation dose to the lung and pneumonitis. This work investigates the relationship between lung dose and the development of radiographic lung changes following stereotactic body radiotherapy (SBRT). In addition, the lung dose and radiographic changes were investigated for their ability to predict the development of clinical grade ≥2 radiation pneumonitis (RP≥2). Regions of consolidation (dense) and ground-glass opacities (hazy) were semi-automatically contoured on 262 3- and 6-month post treatment CT-scans for 145 subjects who underwent SBRT between 2008 and 2018 receiving 40-60 Gy in 3-10 fractions. 84% of the subjects received 48Gy in 4 fractions. RP≥2 was diagnosed in 9 patients (6%). The PTV volume, relative and absolute lung volumes irradiated within defined dose bins were extracted from the treatment plans. Volumes of dense and hazy radiographic changes, both absolute volumes in mL and volumes normalized by the PTV volume were assessed at 3- and 6-months. Correlations for all 3- and 6-month hazy and dense volumes with PTV volumes, relative and absolute lung volumes in defined dose bins, and treatment technique (3D conformal radiotherapy (3DCRT), static intensity modulated radiotherapy (IMRT), or volumetrically modulated arc therapy (VMAT)) were established through Spearman correlation using Bonferroni correction. Univariate logistic models, using the Firth small sample bias correction, were developed for predicting RP≥2. PTV volume and relative lung dose bins between 25 and 40 Gy were significantly correlated with the hazy and dense volumes on both the 3 and 6 month images (p=<0.0001-0.0019). There was no significant difference in the hazy or dense volumes at either 3- or 6-months by the treatment technique. Subjects developing RP≥2 on average demonstrated a 2- to 4-fold increase in the hazy and dense absolute and normalized volumes at both 3- and 6-months (n.s.). The 3-month dense (p=0.03), 6-month dense (p=0.02), 6-month dense normalized (p=0.04), and 6-month hazy volumes (p=0.03) were significantly correlated with RP≥2 in univariate logistic models (AUC 0.64-0.67). Lung V20-40Gyappears to be correlated with radiographic changes following lung SBRT. While irradiated lung volumes were not correlated with RP≥2, the amount of dense volume present at 3 and 6 months in particular appears to be related to the development of RP≥2. This observation indicates that in addition to dose, demographic and clinical factors may influence the development of RP and need to be further investigated.

Truncation of the PTV for Minimization of Risk of Chest Wall Toxicity in Patients Receiving SBRT for Stage I NSCLC

Chest wall toxicity, including chest wall pain and rib fracture, is a known potential complication of stereotactic body radiation therapy (SBRT) for non-small cell lung cancer (NSCLC), impacting 10 – 40 % of patients. Smaller tumor-to-chest wall distance has been identified as a risk factor for chest wall pain after SBRT. While the standard planning target volume (PTV) is typically a uniform expansion on the gross/ internal target volume (GTV/ITV), for selected patients with tumors within 5 mm of the chest wall, we plan and deliver SBRT using a truncated PTV along the chest wall. The aims of this study were to identify outcomes and toxicities associated with use of a truncated PTV along the chest wall. We retrospectively analyzed the records of patients with stage I (T1-2aN0M0) NSCLC who received SBRT from 6/2009 to 7/2016. Patients were immobilized with a custom vacuum bag. 4-dimensional CT (4DCT) was performed. A uniform 5 mm expansion of the ITV was generated for the PTV. When this expansion overlapped with the chest wall, the region of overlap was removed from the PTV. SBRT was delivered using 3D conformal radiotherapy, intensity-modulated radiotherapy, or volumetric arc therapy on a treatment couch with six degrees of freedom with cone-beam CT (CBCT) guidance. Respiratory gating or abdominal compression were used in selected cases. For each fraction, typically at least 2 CBCTs were obtained to assess for intrafraction motion. Descriptive statistics were used to analyze outcomes. The study was approved by the IRB. Median follow-up was 36.8 months. 276 tumors were treated in 240 patients. 241 tumors were peripheral tumors and ITVs for 127 tumors (46.0%) were located within 5 mm of the chest wall. Of these, 67 tumors (52.8%) directly abutted the chest wall. Median ITV was 6.5 cc (range 0.6 – 80 cc) and median PTV was 19.5 cc (range 4.2 – 126.0 cc). Median total dose to the ITV was 48 Gy (range 48 – 60 Gy) in 4 (range 3 – 5) fractions. For the chest wall, the median V30 was 10.5 cc (range 2 – 38.8 cc), median V40 was 1.4 cc (range 0 – 23.2 cc), and median Dmax was 50Gy (range 43.8 – 60 Gy). For tumors directly abutting the chest wall, the chest wall median V30 was 11.6 cc (2.1 – 38.8 cc), median V40 was 2.9 cc (0.1 – 23.2 cc) and median Dmax was 51 Gy (45.8 – 60 Gy). The rate of chest wall pain attributable to SBRT was 1.7%. The rate of rib fracture attributable to SBRT was 4.1%; of those, only 2/10 patients reported pain. There were 15 local recurrences, and 3-year local control was 92.7%. Truncation of the PTV to avoid overlap with the chest wall in peripheral NSCLC was not associated with increased risk of local failure. There were minimal rates of chest wall toxicity despite a high percentage of tumors directly abutting the chest wall. Rigid immobilization and use of multiple CBCTs for assessment of intrafraction motion are critical when using a truncated PTV. In carefully selected patients, this is an excellent option for minimizing chest wall toxicity without compromising local control.

NTCP Modeling of Xerostomia Related to Parotid Dose from Whole-Brain Radiation Therapy

We recently reported an association between parotid dose and xerostomia in patients receiving whole brain radiation therapy (WBRT). The purpose of this analysis is to perform normal tissue complication probability (NTCP) modeling to further explore the parotid dosimetric indices associated with patient-reported xerostomia. Patients receiving WBRT (25-40 Gy in 10-20 fractions) for any diagnosis were enrolled on a prospective observational study. WBRT was delivered with 3D-conformal radiation therapy using standard opposed lateral fields covering C1. The parotids were not prospectively delineated, but retrospectively delineated and considered one structure for analysis. Patients completed the University of Michigan Xerostomia Questionnaire (Xerostomia score, scaled 0-100, higher is worse) and a 4-point dry mouth “bother” score (1-Not at all, 2-A little, 3-Quite a bit, 4-Very much) at baseline, conclusion of WBRT, 2 weeks, 1 month (primary endpoint), 3 months, and 6 months post-WBRT. The clinical data were fitted by the Lyman-Kutcher-Burman (LKB) and Relative Seriality (RS) NTCP models using outcomes at 1 month post-RT. We defined toxicity as a ≥20 point worsening in xerostomia score, or a ≥2 point worsening in bother score. 55 patients who reached the primary time point of 1 month were eligible for analysis. Median WBRT dose was 30 Gy in 10 fractions. Median parotid mean dose was 17Gy (Range, 11-28Gy) and median parotid V20Gy was 48% (Range, 24-84%). Xerostomia score increased by ≥20 in 19 patients (35%), and bother score increased by ≥2 points in 11 patients (20%). Parotid V5Gy-V20Gy were found to correlate best with toxicity, with AUC 0.68 for xerostomia score and 0.69 to 0.71 for bother score. AUC values for parotid mean dose were 0.64 and 0.65 for xerostomia score and bother score respectively. The values for the D50, m and n parameters of the Lyman-Kutcher-Burman model were 22.3Gy, 0.84 and 1.0, respectively for xerostomia score and 28.4Gy, 0.55 and 1.0 for bother score. Similarly, the values for the D50, γ and s parameters of the Relative Seriality model were 23.5Gy, 0.28 and 0.0001, respectively for xerostomia score and 32.0Gy, 0.45 and 0.0001 for bother score. A statistically significant toxicity Odds Ratio of 8.6 and 9.1 was observed in patients with parotid V20Gy > 48% for xerostomia score and bother score, respectively. Clinically significant xerostomia was fairly common after WBRT and correlated well with parotid V5Gy-V20Gy. The dose-response for xerostomia could be determined by fitting the clinical data with the LKB and RS NTCP models. These data support the need for minimization of parotid dose in patients receiving WBRT. Additionally, they can be very useful in prospective treatment plan optimization and evaluation.

A Comparison of Radiation Techniques in Patients Treated with Concurrent Chemoradiation for Stage III Non-Small Cell Lung Cancer

The standard of care in the management of stage III non-small cell lung cancer (NSCLC) is concurrent chemoradiation. Recently, newer more conformal techniques with intensity modulated radiation therapy (IMRT) and volumetric arc therapy (VMAT) are being used. It is unclear whether a more conformal technique ultimately improves survival in patients with stage III lung cancer. We looked at population-based data to examine this question. A retrospective cohort of stage III NSCLC patients treated with concurrent chemoradiation with curative intent between 2009-2014 in Ontario were identified from the ICES (Institute of Clinical Evaluative Sciences) database. Patients were excluded if they had surgery, sequential chemoradiation or radiation alone. Outcomes were compared for patients treated with 3D conformal radiation (3D-CRT), IMRT and VMAT. The primary endpoint was overall survival (OS), calculated using the Kaplan-Meier method and compared using log-rank test. Cox regression was used to investigate effect of radiation type on OS. A minimal clinically important difference (MCID) was set at ≥15%. Between 2009-2014, a total of 2507 patients were treated with 3D-CRT (N=925), IMRT (N=1227) or VMAT (N=355). The rate of 3D-CRT use declined (from 65% in 2009 to 14% in 2014) while the rates of IMRT (35% to 53%) and VMAT (0% to 33%) use concurrently increased. Median survival in months was 22.7 [95% CI 21.0-24.4] for 3D-CRT, 20.8 [95% CI 19.6-22.2] for IMRT and 24.3 [95% CI 20.6-27.9] for VMAT (p=0.041 for all 3 groups, and p=0.046 for 3D CRT vs IMRT alone). The 5 year OS was 22.1% [95% CI 19.2-25.1] for 3D-CRT vs 18.1% [95% CI 15.4-20.9] for IMRT (p=0.046). Prognostic factors for survival on multivariable analysis included male sex [HR 1.29, 95% CI 1.18-1.42, p <0.001], income quintile [HR 0.95, 95% CI 0.92-0.99, p = 0.004], age [HR 1.03, 95% CI 1.00-1.06, p = 0.04], and radiation type [IMRT HR=1.12, 95% CI 1.01-1.24; VMAT HR=0.91, 95% CI 0.76-1.09, p=0.012]. There is increased uptake of more conformal techniques over time amongst stage III NSCLC patients. Although a statistically significant difference in OS was observed, this was likely driven by unmeasured patient selection effects. Absolute differences were modest and did not meet clinical significance.

Chemoradiation Phase II Trials: Re-Exploring a World of Missed Opportunities

Although crucial limitations were identified when concurrent chemoradiation (cCRT) phase III trials characteristics were assessed, characteristics of cCRT phase II trials have never been reported. The objective was to describe features of all cCRT phase II trials. Requests were performed in the Medline database (via PubMed) using MESH terms: “clinical trials: phase II as topic”, “chemoradiotherapy”. 458 cCRT phase II trials were identified, mainly with multicenter (51.5%), single arm studies (77.7%) published after 2011 (55.0%). The median number of included patients was 52. Primary endpoints were mainly response rate (20.5%) and pathological complete response (14.4%). The primary endpoint was not defined in 22% of studies. Tumors were mostly lung (23.1%) and head and neck (20.3%) cancers treated at a locally advanced setting (81.7%). 55.2% of trials used 3D-conformal radiotherapy and 9.1% intensity-modulated radiotherapy, mainly with normo-fractionation (82.0% of the 573 arms with radiotherapy). Radiation technique was not reported in 19.9% of studies. Associated anticancer drugs (563 arms) were mainly conventional chemotherapies (559 arms): cisplatin (46.2%) and 5-fluorouracil (28.3%). Non cytotoxic agents (targeted therapies, immunotherapies) were tested in 97 arms (17%). With a median follow-up of 31 months, acute grade 3–5 were reported in 98.5% of studies and late toxicities in 44.5%. Follow-up was not reported in 17% of studies. cCRT Phase II trials featured severe limitations, with outdated radiation techniques, insufficient reporting of crucial data and a small number of included patients. This certainly hindered the development of successful phase III trials.

UNCONVENTIONAL FRACTIONATION RADIOTHERAPY REGIMENS IN TREATMENT OF INOPERABLE LUNG CANCER

The purpose of the study was to compare the efficacy and toxicity of hypofractionated versus hyperfractionated radiotherapy in patients with inoperable lung cancer.Material and Methods. Patients with inoperable lung cancer, who were treated between 2014 and 2017, were assigned to undergo radiotherapy in two arms: accelerated hypofractionated conformal radiotherapy arm with 70 patients (60 Gy in 25 fractions, with 2.4 Gy per fraction) and accelerated hyperfractionated radiotherapy with 49 patients (60–70 Gy with 1–1.5 Gy per fraction). At the same time, platinum-based chemotherapy was applied.Results. The rates of partial response, complete response, stable disease and progressive disease were 44.3, 7.2, 38.5 and 10.0 %, respectively in patients with hypofractionated conformal radiotherapy arm. The corresponding values were 71.4, 6.1, 16.4 and 6.1 %, respectively in patients with hyperfractionated radiotherapy arm. The 2-year overall survival rate was 62.8 % for the hypofractionated group and 58.1 % for the hyperfractionated group. Esophagitis III grade was observed in 4 (5.7 %) patients of the hypofractionated group and in 3 (6.5 %) patients of the hypofractionated group. Pneumonitis III grade was reported in 2 (2.9 %) patients in the hypofractionated radiotherapy arm and in 4 (8.7 %) patients in the hyperfractionated radiotherapy arm.Conclusion. Results of the study showed that 3D-conformal hypofractionated radiotherapy combined with concurrent chemotherapy resulted no in severe radiation-induced complications, and demonstrated satisfactory short-and long-term treatment outcomes.

IMRT Reduces Acute Toxicity in Patients Treated with Preoperative Chemoradiation for Gastric Cancer

Two large randomized trials are currently investigating preoperative chemoradiation for localized gastric adenocarcinoma. However, radiation therapy (RT) can be associated with relatively high rates of acute toxicity. Newer techniques, such as intensity modulated RT (IMRT), could reduce toxicity by reducing radiation dose to normal structures. Our goal was to compare rates of toxicity, toxicity-related events, and oncologic outcomes in patients treated with IMRT compared to 3D conformal RT (3DCRT). The records of 202 gastric cancer patients treated with preoperative intent RT at our institution from 1998-2018 were retrospectively reviewed. Demographic data, treatment details, acute and late toxicities (CTCAE 4.0), progression and survival data were recorded. Patients who had stage IV disease were excluded. Statistical analysis included descriptive statistics, Cox regression analysis, and Kaplan-Meier survival. 54% were male, and the median age was 63. 82 patients received 3DCRT and 120 patients received IMRT. The median radiation dose was 45Gy (IQR: 45-45 Gy). 78% of patients in the 3DCRT group and 95% of patients in the IMRT group received neoadjuvant chemotherapy prior to RT (p=0.001). 99% of patients in both groups received concurrent chemotherapy. There were no significant differences between the 3DCRT and IMRT groups with respect to gender, race, histology, tumor, or nodal stage. The rate of grade 3-4 acute toxicity was significantly lower in patients treated with IMRT compared to those treated with 3DCRT (53% vs. 73%, p=0.004). The composite rate of toxicity-related events (hospitalization, feeding tube, IV rehydration or RT breaks) was also significantly lower in patients treated with IMRT compared to 3DCRT (56% vs. 85%, p<0.001). 73% of patients who received 3DCRT and 68% of patients who received IMRT underwent subsequent surgical resection (p=0.245). Among patients who underwent surgical resection, there was no significant difference in the rate of positive margins between those who received 3DCRT and those who received IMRT (7% vs 15%, p=0.13). Among patients who underwent surgical resection, the 3-year OS and PFS rates were not significantly different in patients receiving 3DCRT compared to IMRT (OS 73% vs. 73%, p=0.93, PFS 65% vs. 64%, p=0.68). Among patients who did not undergo surgical resection, the 3-year OS and PFS rates were also not significantly different in patients receiving 3DCRT compared to IMRT (OS 27% vs. 28%, p=0.93; PFS 19% vs. 14%, p=0.69). Our study indicates a reduction in the rates of grade 3-4 acute toxicity and toxicity-associated events in patients treated with IMRT compared to 3DCRT, with no significant difference in oncologic outcomes. These findings suggest that IMRT should be considered as the preferred radiation modality in patients treated with preoperative chemoradiation for gastric cancer.

Risk Factors Associated with Lymphocyte Reduction during Radiotherapy in Patients with Limited Stage Small Cell Lung Cancer

We have recently demonstrated that lymphocyte reduction, i.e. lymphopenia, is common during radiation therapy (RT) and is associated with survival in patients with small cell lung cancer (SCLC). This report examines the risk factors contributing to the severity of the treatment induced lymphopenia. We hypothesize that radiation doses to the major normal tissues particularly circulating lymphocytes, play an important role on lymphopenia. This is a retrospective analysis of 582 LS-SCLC patients treated from one single institution during 2013 to 2017.All patients received definitive chemoradiation and had at least three time points of a complete blood count test including a baseline test. The dosimetry parameters for the Planning Target Volume (PTV), RT timing, dose fractionation, RT technique in terms of 3D conformal radiation therapy (3DCRT) versus intensity modulated radiation therapy (IMRT) and important Organs At Risk (OARs) like heart, lung and the total body were analyzed. Effective dose to immune cells (EDIC) was estimated based on these dosimetry parameters. The primary end point was lymphocyte reduction, which was represented by the absolute count of the lymphocyte nadir, percentage of nadir over baseline, and the timing of the lymphocyte nadir. Linear regression was used to examine the significance of the clinical and dosimetry factors on lymphocyte nadir. A total of 582 patients met the study inclusion criteria. The mean absolute lymphocyte counts (ALC’s) were 1.65K (95% CI 0.97-2.30K), 0.94K (95% CI 0.56-1.32K), 0.67K (95% CI 0.38-0.98K) and 0.61K (95% CI 0.33-0.89K) at baseline, 2, 4 and 6 weeks from the start of treatments, respectively. Radiation induced lymphopenia occurred in 414 (66.5%) patients and reached a nadir at median of 4 (95% CI 2.4-5.5) weeks from radiation start. Univariate analysis revealed the clinical stage, body mass index (BMI), use of concurrent chemotherapy, number of chemotherapy cycles before radiotherapy, baseline ALC, RT treatment time, RT technique (3DCRT vs. IMRT), RT fractionation, the total dose of RT and mean dose of lung, heart and total body, and EDIC were all significantly associated with the lymphocyte nadir (all p-values<0.05). Multiple linear regressions showed that clinical stage, baseline ALC, RT technique (CRT vs. IMRT), use of concurrent chemoradiation, the number of chemotherapy cycles before RT, the mean lung dose, the integral total body dose, and EDIC were significant for the lymphocyte nadir. This study of 582 patients demonstrated that many independent risk factors are associated with lymphopenia during RT, as outlined above. These include several treatment related factors that can be modified for improvement.

Quantifying Temporal Trends and the Impact of Advances in Radiation Planning on Heart and Lung Dose for Lung Cancer Treatment Using a Machine Learning Model

Advances in radiotherapy (RT) planning have improved our ability to treat locally advanced non-small cell lung cancer (LA-NSCLC) while limiting damage to normal tissue. Machine learning models may further improve our RT planning by incorporating historic treatment insights to inform the optimal RT plan. We used such a model to quantitatively assess the impact of changes in planning techniques for LA-NSCLC on dose to critical normal tissues. Treatment data from 232 patients with LA-NSCLC treated from 2010-2018 with conventionally fractionated 3D conformal RT (3DCRT) or intensity modulated RT (IMRT)/volumetric modulated arc therapy (VMAT) was collected. A was used to predict patient-specific dosimetric data was built using a validating boosting framework that incorporates feature selection to avoid overfitting, utilizing a library of RT plans and patient features including anatomic information, clinical data, and RT prescription and delivery data. A hindcast model was created with patient data from 2016-2018, and used to predict heart and lung dose for patients treated from 2010-2012 and 2013-2015. To test algorithm integrity, a forecast model was created with data from 2010-2012, and used to predict heart and lung dose for patients from the subsequent era. Predicted and delivered dose metrics were compared using t-tests. From 2010-2012, 40 patients (85%) were treated with 3DCRT and 7 (15%) with IMRT/VMAT. From 2013-2015, 41 patients (53%) were treated with 3DCRT and 37 (47%) with IMRT/VMAT. From 2016-2018, 22 patients (21%) were treated with 3DCRT and 85 (79%) with IMRT/VMAT. The table shows predicted and delivered heart and lung dose metrics for the two models, stratified by treatment era. Predicted heart and lung metrics, except lung V5 Gy, were in general significantly lower than delivered metrics when using a model created with modern treatment planning techniques on earlier patient data, and vice versa. This is likely due to advances in RT planning techniques, particularly with increased adoption of and experience with IMRT/VMAT. Clinical decision support tools such as this may help leverage experience from prior plans to reduce dose to normal tissue such as the heart and lungs, thereby reducing RT toxicity.Abstract 2301; Table 1Mean heart dose (Gy)Mean lung dose (Gy)Lung V5 Gy (%)Lung V20 Gy (%)Hindcast Model Built on 2016-2018 PlansEraPredictedDeliveredPPredictedDeliveredPPredictedDeliveredPPredictedDeliveredP2010-20128.549.710.0312.8513.720.0140.638.80.0921.4823.130.022013-20159.5610.470.0413.6313.610.4743.8341<0.0122.7622.780.482016-20189.59.50.514.1114.110.548.7748.770.523.7823.780.5Forecast Model Built on 2010-2012 Plans2010-20129.719.710.513.7213.720.538.838.80.523.1323.130.52013-201510.7610.470.321413.610.1139.98410.1823.3322.780.22016-201810.699.5<0.0114.6414.110.0141.4448.77<0.0124.0223.780.32 Open table in a new tab