Use Of Intensity-modulated Radiotherapy Research Articles

Comparison of prone and supine positioning for breast cancer radiotherapy using REQUITE data: dosimetry, acute and two years physician and patient-reported outcomes

Objective Most patients receive whole breast radiotherapy in a supine position. However, two randomised trials showed lower acute toxicity in prone position. Furthermore, in most patients, prone positioning reduced doses to the organs at risk. To confirm these findings, we compared toxicity outcomes, photographic assessment, and dosimetry between both positions using REQUITE data. Methods REQUITE is an international multi-centre prospective observational study that recruited 2069 breast cancer patients receiving radiotherapy. Data on toxicity, health-related quality of life (HRQoL), and dosimetry were collected, as well as a photographic assessment. A matched case control analysis compared patients treated prone (n = 268) versus supine (n = 493). Exact matching was performed for the use of intensity-modulated radiotherapy, boost, lymph node irradiation, chemotherapy and fractionation, and the nearest neighbour for breast volume. Primary endpoints were dermatitis at the end of radiotherapy, and atrophy and cosmetic outcome by photographic assessment at two years. Results At the last treatment fraction, there was no significant difference in dermatitis (p = .28) or any HRQoL domain, but prone positioning increased the risk of breast oedema (p < .001). At 2 years, patients treated in prone position had less atrophy (p = .01), and higher body image (p < .001), and social functioning (p < .001) scores. The photographic assessment showed no difference in cosmesis at 2 years (p = .22). In prone position, mean heart dose (MHD) was significantly lower for left-sided patients (1.29 Gy vs 2.10 Gy, p < .001) and ipsilateral mean lung dose (MLD) was significantly lower for all patients (2.77 Gy vs 5.89 Gy, p < .001). Conclusions Prone radiotherapy showed lower MLD and MHD compared to supine position, although the risk of developing breast oedema during radiotherapy was higher. At 2 years the photographic assessment showed no difference in the cosmetic outcome, but less atrophy was seen in prone-treated patients and this seems to have a positive influence on the HRQoL domain of body image.

The Correlation Between Lymphocyte Nadir and Radiation Therapy for Soft Tissue Sarcoma: Defining Key Dosimetric Parameters and Outlining Clinical Significance

The objectives of this study were to identify key dosimetric parameters associated with postradiation therapy lymphopenia and uncover any effect on clinical outcomes. This was a retrospective review of 69 patients (between April 2010 and January 2023) who underwent radiation therapy (RT) as a part of curative intent for soft tissue sarcoma (STS) at a single academic institution. All patients with treatment plans available to review and measurable absolute lymphocyte count (ALC) nadir within a year after completion of RT were included. Median follow-up was 22 months after the start of RT. A decrease in lymphocyte count was noted as early as during treatment and persisted at least 3 months after the completion of RT. On multivariable linear regression, the strongest correlations with ALC nadir were mean body dose, body V10 Gy, mean bone dose, bone V10 Gy, and bone V20 Gy. Five-year overall survival was 60% and 5-year disease-free survival was 44%. Advanced T-stage, chemotherapy use, use of intensity-modulated RT, lower ALC nadir, and the development of grade ≥2 lymphopenia at nadir were associated with worse overall survival and disease-free survival. Post-RT lymphopenia was associated with worse outcomes in STS. There were associations between higher body V10 Gy and bone V10 Gy and lower post-RT ALC nadir, despite the varying sites of STS presentation, which aligns with the well-known radiosensitivity of lymphocyte cell lines. These findings support efforts to reduce treatment-related hematopoietic toxicity as a way to improve oncologic outcomes. Additionally, this study supports the idea that the effect of radiation on lymphocyte progenitors in the bone marrow is more significant than that on circulating lymphocytes in treatments with limited involvement of the heart and lung.

The use of 18F-FDG PET/CT for radiotherapy treatment planning in non-small cell lung cancer: a mini-review

: In the past decades, the technical achievements in radiotherapy treatment planning and delivery, such as the use of intensity-modulated radiotherapy or the use of image-guided radiotherapy, alongside with the significant developments in molecular imaging and especially the use of positron-emission tomography (PET) have significantly improved radiotherapy treatment precision. In non-small cell lung cancer (NSCLC), the use of 18F-fluoro-desoxy-glucose (18F-FDG) positron-emission tomography/computed tomography (18F-FDG-PET/CT) has a high accuracy for diagnostic workup, staging and response assessment but has been also implemented to optimize target volume concepts in NSCLC with high precision. These advances led, in the recent years, to an increased tumor control and improved outcomes. Especially in the context of emerging systemic treatments, such as immune checkpoint blockades (ICBs), the prevention of unnecessary irradiation of the lymphatic system might be very important. In the past years, several prospective randomized studies have been performed, aiming to optimize, standardize and develop new concepts in the target volume delineation especially in locally advanced NSCLC using different approaches. While the PET-Plan trial used a uniform target volume reduction based on the 18F-FDG-PET/CT signal in the experimental arm, the PET boost trial and the RTOG 1106 used the 18F-FDG-PET/CT information to define an additional boost volume for dose escalation. Within this mini-review, we provide an overview on the role of 18F-FDG-PET/CT, the challenges and the benefits, in radiotherapy of NSCLC.

Dose-escalated pancreas radiotherapy for unresected pancreatic adenocarcinoma: Patterns of care and survival in the United States.

676 Background: Randomized trials have not shown an overall survival (OS) benefit to adding radiotherapy (RT) to chemotherapy for patients with locally advanced pancreatic adenocarcinoma (LAPC). However, trials such as LAP07 did not incorporate escalated-dose RT (EDR), which may confer longer survival. The adoption of EDR across the United States and associated outcomes are unknown. Methods: We queried the National Cancer Data Base for non-surgically managed patients with LAPC diagnosed between 2004 and 2019. RT with biologically effective doses (BED10) &gt; 70 and ≤ 200 Gy were labeled EDR and conventional-dose RT (CDR) for 39-70 Gy doses. Associations with receipt of EDR and with OS were identified using multivariate analysis (MVA) logistic and Cox regressions, respectively. Bonferroni corrections were applied. Cochran-Armitage and Mann-Kendall trend tests were performed to assess trends in use of RT. Results: Of 64,303 patients, the most common treatments were chemotherapy alone (CT) (71%), chemoradiation (CRT) (27%), and pancreas RT alone (2%). 18,970 patients received pancreas RT, of which 91% was CDR (median dose 50.4 Gy; median 28 fractions) and 9% was EDR (50 Gy; 5 fractions). Use of pancreas RT increased from 14% in 2004 to a peak of 18% in 2010, decreased to a nadir of 13% in 2016, and subsequently increased to 15% by 2019 ( Ptrend &lt; 0.001). EDR use increased from 7% in 2004 to 22% in 2019 ( Ptrend &lt; 0.0001). Median BED10 increased from 53 to 59 Gy ( Ptrend&lt; 0.001). Of patients receiving pancreas RT, use of intensity-modulated RT (IMRT) and stereotactic body RT (SBRT) respectively increased from 25% and 2% in 2004 to 60% and 27% in 2019, while use of 3-D conformal RT (3D-CRT) decreased from 64% to 9% ( Ptrend &lt; 0.02 for all comparisons). On MVA logistic regression, primary tumor location in the body/tail vs. head (aOR 1.22, 95% CI 1.07-1.40; P = 0.003) associated with greater EDR receipt, whereas T3-4 vs. T2 disease (aOR 0.81, CI 0.71-0.92; P = 0.002) associated with lesser receipt. At a median follow up of 59.1 months (CI 57.5-61.0), median OS estimates for CDR and EDR were 10.2 months (CI 10.1-10.3) and 13.3 months (CI 13.2-13.5; P &lt; 0.0001), respectively. On MVA Cox regression, N1 vs. N0 disease (HR 1.08, CI 1.06-1.10; P &lt; 0.001) correlated with higher risk of death, whereas CRT vs. CT (HR 0.83, CI 0.81-0.85; P &lt; 0.001) correlated with lower risk of death. Subset MVA of 14,634 CRT patients correlated higher RT dose—as both a categorical variable (EDR vs. CDR; HR 0.84, CI 0.79-0.90; P &lt; 0.001) and continuous variable (BED10; HR 0.994, CI 0.992-0.995; P &lt; 0.001)—with lower risk of death. Conclusions: Fewer than 1 in 6 patients with unresected LAPC received pancreas RT, despite a nominal increase in utilization in recent years. Although retrospective, these NCDB data suggest longer OS with the addition of RT for unresected LAPC, suggesting continued unmet need. EDR is associated with longer survival vs. CDR.

High weekly integral dose and larger fraction size increase risk of fatigue and worsening of functional outcomes following radiotherapy for localized prostate cancer.

We hypothesized that increasing the pelvic integral dose (ID) and a higher dose per fraction correlate with worsening fatigue and functional outcomes in localized prostate cancer (PCa) patients treated with external beam radiotherapy (EBRT). The study design was a retrospective analysis of two prospective observational cohorts, REQUITE (development, n=543) and DUE-01 (validation, n=228). Data were available for comorbidities, medication, androgen deprivation therapy, previous surgeries, smoking, age, and body mass index. The ID was calculated as the product of the mean body dose and body volume. The weekly ID accounted for differences in fractionation. The worsening (end of radiotherapy versus baseline) of European Organisation for Research and Treatment of Cancer EORTC) Quality of Life Questionnaire (QLQ)-C30 scores in physical/role/social functioning and fatigue symptom scales were evaluated, and two outcome measures were defined as worsening in ≥2 (WS2) or ≥3 (WS3) scales, respectively. The weekly ID and clinical risk factors were tested in multivariable logistic regression analysis. In REQUITE, WS2 was seen in 28% and WS3 in 16% of patients. The median weekly ID was 13.1 L·Gy/week [interquartile (IQ) range 10.2-19.3]. The weekly ID, diabetes, the use of intensity-modulated radiotherapy, and the dose per fraction were significantly associated with WS2 [AUC (area under the receiver operating characteristics curve) =0.59; 95% CI 0.55-0.63] and WS3 (AUC=0.60; 95% CI 0.55-0.64). The prevalence of WS2 (15.3%) and WS3 (6.1%) was lower in DUE-01, but the median weekly ID was higher (15.8 L·Gy/week; IQ range 13.2-19.3). The model for WS2 was validated with reduced discrimination (AUC=0.52 95% CI 0.47-0.61), The AUC for WS3 was 0.58. Increasing the weekly ID and the dose per fraction lead to the worsening of fatigue and functional outcomes in patients with localized PCa treated with EBRT.

Adenoid Cystic Carcinoma of the Head and Neck: Patterns of Recurrence and Implications for Radiotherapy

<h3>Purpose/Objective(s)</h3> Radiotherapy (RT) plays a central role in locoregional control for adenoid cystic carcinoma of the head and neck (ACC). Guidelines on the optimal RT dose, treatment volumes, and modality are lacking in the highly conformal era. We sought to evaluate ACC patterns of recurrence to assess the efficacy of highly conformal RT and optimize target volumes and dose. <h3>Materials/Methods</h3> We identified all patients with ACC consecutively treated at our institution with curative-intent adjuvant or definitive RT from 2005 to 2021 and recorded local (LR) and distant metastasis (DM) events. RT plans were compared to diagnostic imaging to identify in-field, out-of-field, and marginal LRs. Marginal LRs were defined as those within the 50 Gy isodose line but outside of the CTV. <h3>Results</h3> Ninety-nine patients were included. Median follow-up was 5.1 years (IQR: 2.2-9.0). Eighty (80.8%) patients underwent surgery prior to RT. Dose was <60 Gy (10, 10.1%), 60 Gy (49, 49.5%), >60/<70 Gy (19, 19.2%), or 70 Gy (21, 21.2%). CTVs included at least one lymph node level in 61 (61.6%) patients. CTVs tracked along cranial nerves (CN) in 67 (67.7%) patients, with 61 (61.6%) receiving RT to CN V and 43 (43.4%) to CN VII. CN were tracked to the skull base and brainstem in 46 (46.5%) and 21 (21.2%) patients, respectively. Thirty-one (31.3%) patients received intensity modulated proton therapy, with the remainder (68, 68.7%) receiving photon-based intensity modulated radiation therapy. The 2- and 5-year LR risk was 3.6% (95% CI: 1.2-10.9) and 12.2% (6.6-22.7). Predictors of LR on univariate analysis included nasal cavity/nasopharynx location [HR 7.30 (1.17-45.66), <i>p</i>=.034] and primary tumor volume [per 10 cc, HR 1.44 (1.05-1.97), <i>p</i>=.023]. All other factors including concurrent chemotherapy and proton therapy were not associated. Although prescribed RT dose was not significant, 7 of the 10 patients with in-field LRs received ≤60 Gy [50 Gy (n=1), 54 Gy (n=1), 56 Gy (n=1), 60 Gy (n=4)]. Only 2 patients experienced a marginal LR, one with an oral cavity primary that recurred in the mandible bone, and the other with a submandibular primary that recurred in the oropharyngeal mucosa. Only 1 patient each had an out-of-field LR and regional nodal recurrence. Six of the 7 patients with a skull base recurrence (SBR) had coverage of CN to the skull base (n=3) or brainstem (n=3). Six recurred in a treated CN (in-field), and the other recurred in an untreated CN (out-of-field). DM risk was 26.9% (18.9-38.2) and 44.0% (33.8-57.3) at 2- and 5-years, respectively. Median overall survival was 9.2 years. <h3>Conclusion</h3> Modern conformal RT provides excellent locoregional control for patients with ACC. Marginal and out-of-field LRs are rare, validating the use of intensity modulated RT, including proton therapy. Given a low rate of regional nodal recurrence, elective nodal coverage may be omitted in well-selected patients. SBR, while uncommon, occurs primarily in those receiving skull base RT, suggesting a potential role for dose escalation in high-risk patients.

The use of intensity-modulated radiotherapy (IMRT) in the radical treatment of rectal cancer

The use of intensity-modulated radiotherapy (IMRT) in the radical treatment of rectal cancer

Penetrating complications of bevacizumab-containing chemotherapy in previously-irradiated recurrent cervical cancer: a Korean multicenter retrospective study of the Gynecologic Oncology Research Investigators coLLaborAtion (GORILLA) group (GORILLA1001) (036)

<b>Objectives:</b> Gynecologic Oncology Group 240 study showed that incorporating bevacizumab in the treatment of recurrent, persistent, or metastatic cervical cancer conferred overall survival (OS) benefit. However, fistula occurred significantly higher in the bevacizumab (+) group than the chemotherapy alone group. Moreover, all fistulas in the bevacizumab (+) group were developed in patients who were previously irradiated. This study aimed to evaluate the incidence and to identify risk factors for penetrating complications, including gastrointestinal (GI) and genitourinary (GU) fistula/perforation, of bevacizumab plus chemotherapy in recurrent cervical cancer patients who underwent pelvic radiation therapy (RT). <b>Methods:</b> Medical records of the patients with recurrent cervical cancer who previously underwent pelvic radiation at five university hospitals in Korea from 2007 to 2020 were retrospectively reviewed. Women who received chemotherapy immediately after RT were excluded. Clinical-pathologic factors were compared between groups of the following two settings: <i>1)</i> fistula/perforation (+) and (-); <i>2)</i> bevacizumab plus chemotherapy and chemotherapy alone. Univariate and multivariate regression analyses were performed to identify risk factors for penetrating complications. OS was also compared between groups of the two comparisons. <b>Results:</b> Of 219 women with recurrent cervical cancer who previously underwent pelvic RT, 144 (65.8%) received bevacizumab-containing chemotherapy, and 75 (34.2%) received chemotherapy alone. Fistula/perforation of any grade occurred in 36 (16.4%): fistulas alone in 27 (11 GI, 8 GU, and 8 both) and perforations in nine patients. Women receiving bevacizumab experienced fistula/perforation more frequently than those who used chemotherapy alone (20.8% [30/144] vs 8.0% [6/75]; p=0.015) (Table 1). Multivariate regression analysis showed that bevacizumab administration was the only independent risk factor for the occurrence of fistula/perforation. Age, diabetes, hypertension, tumor histology (squamous vs non-squamous), cumulative dose of RT, primary treatment (operation vs. RT vs both), use of intensity-modulated RT, and the time interval between RT and bevacizumab failed to show association with fistula/perforation. During median follow-up of 33.7 months (1.2-185.6 months), significant OS difference was shown neither between bevacizumab (+) versus bevacizumab (-) (HR: 1.03; median 119.8 months [95% CI: 97.3-142.3months] vs 115.7 months [96.0-135.4 months]; p=0.928) nor between fistula/perforation (+) versus fistula/perforation (-) (HR: 1.78; median 84.2 months [59.3-109.0 months] vs 129.5 months [114.1-144.9 months]; p=0.065). <b>Conclusions:</b> The study results suggest that incorporating bevacizumab in the chemotherapy regimen to treat recurrent cervical cancer with a previous history of pelvic RT incurs a considerable risk of GI and/or GU penetrating complications, which might damage the survival outcome as well as the quality of life. The risk and benefit of incorporating bevacizumab in the treatment of previously irradiated recurrent cervical cancer patients are needed to be carefully weighed, considering that effective prevention of the penetrating complications is difficult because of the lack of knowledge regarding other risk factors.

HSD3 Choosing Wisely? Use of Intensity Modulated Radiation Therapy Following Lumpectomy in Early-Stage Breast Cancer: A Seer-Medicare Analysis

The American Society for Radiation Oncology’s (ASTRO) Choosing Wisely (CW) initiative recommends against the routine use of intensity-modulated radiotherapy (IMRT) for whole breast radiotherapy in patients with breast cancer (BC). The impact of CW on use of IMRT in older patients with BC following breast-conserving surgery was evaluated. Also, factors that may predict IMRT use were assessed.

De-escalating elective nodal irradiation for nasopharyngeal carcinoma.

Treatment outcomes for endemic nasopharyngeal carcinoma have steadily improved over the past two decades with routine use of intensity-modulated radiotherapy (IMRT), concurrent chemotherapy, and MRI staging. 1 Peng G Wang T Yang KY et al. A prospective, randomized study comparing outcomes and toxicities of intensity-modulated radiotherapy vs conventional two-dimensional radiotherapy for the treatment of nasopharyngeal carcinoma. Radiother Oncol. 2012; 104: 286-293 Summary Full Text Full Text PDF PubMed Scopus (420) Google Scholar , 2 Blanchard P Lee A Marguet S et al. Chemotherapy and radiotherapy in nasopharyngeal carcinoma: an update of the MAC-NPC meta-analysis. Lancet Oncol. 2015; 16: 645-655 Summary Full Text Full Text PDF PubMed Scopus (459) Google Scholar In the past decade, trials have primarily focused on treatment escalation with induction and consolidative chemotherapy. 3 Zhang Y Chen L Hu GQ et al. Gemcitabine and cisplatin induction chemotherapy in nasopharyngeal carcinoma. N Engl J Med. 2019; 381: 1124-1135 Crossref PubMed Scopus (312) Google Scholar , 4 Pan JJ Ng WT Zong JF et al. Proposal for the 8th edition of the AJCC/UICC staging system for nasopharyngeal cancer in the era of intensity-modulated radiotherapy. Cancer. 2016; 122: 546-558 Crossref PubMed Scopus (164) Google Scholar , 5 Chen YP Liu X Zhou Q et al. Metronomic capecitabine as adjuvant therapy in locoregionally advanced nasopharyngeal carcinoma: a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial. Lancet. 2021; 398: 303-313 Summary Full Text Full Text PDF PubMed Scopus (23) Google Scholar However, with modern treatment, fewer than 20% of patients with non-metastatic nasopharyngeal carcinoma develop disease recurrence. In this population with few competing risks, these excellent outcomes have promoted renewed interest in individualised treatment de-intensification. Elective upper-neck versus whole-neck irradiation of the uninvolved neck in patients with nasopharyngeal carcinoma: an open-label, non-inferiority, multicentre, randomised phase 3 trialElective UNI of the uninvolved neck provides similar regional control and results in less radiation toxicity compared with standard WNI in patients with N0–N1 nasopharyngeal carcinoma. Full-Text PDF

Major adverse cardiac event risk prediction model incorporating baseline Cardiac disease, Hypertension, and Logarithmic Left anterior descending coronary artery radiation dose in lung cancer (CHyLL)

Background and purposeIn patients with locally advanced non-small cell lung cancer (LA-NSCLC) post-radiotherapy, mean heart dose (MHD) and the percent of left anterior descending (LAD) coronary artery receiving ≥15 Gy (LADV15) are associated with major adverse cardiac events (MACE). We developed a MACE prediction model in this population. Materials and MethodsTotal 701 patients with LA-NSCLC treated with curative-intent radiotherapy reviewed, split by diagnosis date into “development” (n = 500) and later (n = 201) “test” cohorts. Development patients were analyzed using a multivariable Cox-proportional hazard model with backward elimination scheme (Bonferroni-adjusted α = 0.025). Potential predictors were selected a priori: age, coronary heart disease (CHD), Framingham Risk, hypertension, MHD, LADV15, intensity modulated radiotherapy use, and CHD and LADV15 interaction (CHD:LADV15). Cardiac doses as quadratic, square root, and logarithmic (ln[X + 1]) forms were explored. Models were internally validated with bootstrapping. ResultsFinal model incorporated CHD, Hypertension, Logarithmic LADV15, and CHD*ln[LADV15 + 1] (CHyLL; β coefficients: 5.51, 1.28, 1.48, −1.36; all p < 0.025; bootstrapping c-index: 0.80; test cohort c-index: 0.76). Possible risk score range: 0–8.11. MACE incidence was 6.8% and 23.6% at 48 months (p = 0.041), and survival rates were 51.6% and 35.0% (p = 0.099), in the low-risk (score <5.00) and high-risk (score ≥5) test groups, respectively. Using the model, calculated LADV15 constraints for patients without CHD were 11.3% and 28.3% for those with and without hypertension, respectively, to remain low-risk. ConclusionsPre-existing CHD, hypertension, and LADV15 were important factors in predicting MACE after radiotherapy. CHyLL has the potential to estimate personalized LADV15 constraints based on cardiac risk factors and acceptable MACE thresholds.

Twice-daily chemoradiotherapy in limited-stage small-cell lung cancer

Acute radiation-induced oesophagitis has been associated with adverse events such as weight loss, substantial effect on quality of life, and reduced survival.1 Concurrent chemotherapy given with hyperfractionated radiation therapy has been associated with an increased incidence of acute oesophageal toxicity.2 Several dosimetric parameters and high doses have been associated with an increased risk of acute oesophagitis.1 However, radiotherapy technical developments (eg, use of intensity-modulated radiotherapy and omission of elective nodal irradiation) allow a reduced dose to the organs at risk, including the oesophagus.

Intensity-modulated radiotherapy combined with intracavitary brachytherapy for locally advanced cervical cancer with uterus didelphys

The purpose of this study was to investigate the clinical application of intensity-modulated radiotherapy combined with intracavitary radiotherapy for locally advanced cervical cancer complicated with uterus didelphys. We retrospectively reviewed the medical records of six patients with locally advanced cervical cancer associated with uterine malformations treated at the National Cancer Center/Cancer Hospital (Beijing, China) between 2015 and 2018. Six cases, including cervical squamous cell carcinoma (n = 3), cervical adenocarcinoma (n = 2), and clear cell adenocarcinoma (n = 1) were identified by pathological diagnosis. Uterine malformation included uterus didelphys (n = 6), with vaginal subseptum (n = 2). Six cases were treated with pelvic intensity-modulated radiotherapy. Four patients received three- dimensional intracavitary brachytherapy based on computed tomography, and two patients received conventional two-dimensional intracavitary brachytherapy. The acute and delayed responses of gastrointestinal and genitourinary toxicities were ≤grade 2 in 5 patients. Five patients achieved clinical complete remission and four patients had no recurrence during the follow-up period. One patient with cervical adenocarcinoma expired due to progression of the disease. The clinical results suggest that advanced cervical cancer associated with uterus didelphys required individual radiotherapy. The use of intensity-modulated radiotherapy combined with three-dimensional intracavitary brachytherapy is recommended in concurrent chemoradiotherapy.

Intensity-modulated Radiotherapy for Rectal Cancer in the UK in 2020

AimsPreoperative (chemo)radiotherapy followed by total mesorectal excision is the current standard of care for patients with locally advanced rectal cancer. The use of intensity-modulated radiotherapy (IMRT) for rectal cancer is increasing in the UK. However, the extent of IMRT implementation and current practice was not previously known. A national survey was commissioned to investigate the landscape of IMRT use for rectal cancer and to inform the development of national rectal cancer IMRT guidance. Materials and methodsA web-based survey was developed by the National Rectal Cancer IMRT Guidance working group in collaboration with the Royal College of Radiologists and disseminated to all UK radiotherapy centres. The survey enquired about the implementation of IMRT with a focus on the following aspects of the workflow: dose fractionation schedules and use of a boost; pre-treatment preparation and simulation; target volume/organ at risk definition; treatment planning and treatment verification. A descriptive statistical analysis was carried out. ResultsIn total, 44 of 63 centres (70%) responded to the survey; 30/44 (68%) and 36/44 (82%) centres currently use IMRT to treat all patients and selected patients with rectal cancer, respectively. There was general agreement concerning several aspects of the IMRT workflow, including patient positioning, use of intravenous contrast and bladder protocols. Greater variation in practice was identified regarding rectal protocols; use of a boost to primary/nodal disease; target volume delineation; organ at risk delineation and dose constraints and treatment verification. Delineation of individual small bowel loops and daily volumetric treatment verification were considered potentially feasible by most centres. ConclusionThis survey identified that IMRT is already used to treat rectal cancer in many UK radiotherapy centres, but there is heterogeneity between centres in its implementation and practice. These results have been a valuable aid in framing the recommendations within the new National Rectal Cancer IMRT Guidance.

The Role of Facility Variation on Racial Disparities in Use of Hypofractionated Whole Breast Radiation Therapy

Hypofractionated radiation therapy is a less burdensome and less costly approach that is efficacious for most patients with early-stage breast cancer. Concerns about racial disparities in adoption of medical advances motivate investigation of the use of hypofractionated radiation in diverse populations. The goal of our study was to determine whether hypofractionated whole breast radiation therapy after breast-conserving surgery was being similarly used across racial groups in the state of Michigan. A prospectively collected statewide quality consortium database from 25 institutions was queried for patients with breast cancer who completed hypofractionated (HF) or conventionally fractionated whole breast radiation therapy from January 2012 to December 2018. We used patient-level multivariable modeling to evaluate associations between HF use and race, controlling for patient and facility factors, and multilevel modeling to account for patient clustering within facilities. Of 9634 patients analyzed, 81% self-reported race as white, 17% as black, and 2% as Asian, similar to statewide and national distributions. In addition, 31.7% of whites were treated at teaching centers compared with 66.7% of blacks and 64.8% of Asians. In 2018, HF was used in 72.7% of whites versus 56.7% of blacks and 67.6% of Asians (P = .0411). On patient-level multivariable analysis, black and Asian races were significantly associated with a lower likelihood of HF receipt (P < .001), despite accounting for treatment year, age, laterality, body mass index, breast volume, comorbidities, stage, triple-negative status, intensity modulated radiation therapy use, teaching center treatment, and 2011 American Society for Radiation Oncology Hypofractionation Guideline eligibility. On multilevel analysis, race was no longer significantly associated with HF receipt. We observed that black and Asian patients receive hypofractionated whole breast radiation therapy less often than whites, despite more frequent treatment at teaching centers. Multilevel modeling eliminated this disparity, suggesting that differences in facility-specific HF use appear to have contributed. Further inquiry is needed to determine whether reduction of facility-level variation may reduce disparities in accessing HF treatment.

Management of Chemotherapy for Stage II Nasopharyngeal Carcinoma in the Intensity-Modulated Radiotherapy Era: A Review.

Nasopharyngeal carcinoma is an endemic disease with a high prevalence in Southeast Asia, Mediterranean countries, and Northern Africa. With substantial advances in screening and diagnosis, increasingly more early-stage (stage I~II) patients are being diagnosed. The undebated treatment modality for stage I patients is radiotherapy alone. However, controversies exist for patients with stage II disease, mostly revolving around the management of chemotherapy. However, the use of intensity-modulated radiotherapy for the treatment of nasopharyngeal carcinoma has increased recently, which has drastically improved survival outcomes. Thus, many oncologists have considered omitting chemotherapy for stage II patients in the intensity-modulated radiotherapy era. Unfortunately, prospective studies comparing concurrent radio-chemotherapy with intensity-modulated radiotherapy alone are limited. Notably, stage II nasopharyngeal carcinoma consists of three subgroups, among which stage T2N1M0 disease is unique and potentially warrants additional treatment including chemotherapy. Additionally, molecular biology techniques are advancing at an incredible speed. Instead of adopting a one-size-fits-all recommendation, exploring potential predictive biomarkers to select patients who are likely to derive benefit from chemotherapy is a better choice. In this review, we summarize the data from studies and reviews regarding chemotherapy for stage II nasopharyngeal carcinoma in the intensity-modulated radiotherapy era and discuss chemotherapy utility. Eventually, we conclude that IMRT alone may be sufficient for stage II nasopharyngeal carcinoma, but this needs to be verified by prospective studies in the near future, the evidence collected thus far suggests that concurrent chemo-radiotherapy without induction or adjuvant chemotherapy is yet to be necessary for patients with stage II disease.

The financial impact of fractionation scheme and treatment planning method for rectal cancer in the United States.

6518 Background: Preoperative long-course chemoradiotherapy (CRT) and short-course radiotherapy (SCR) for locally advanced rectal cancer (LARC) were found to have equivalent outcomes in three randomized trials. SCR may have lower acute toxicity and the down-staging following CRT is more well-established. At present, SCR is frequently used in Europe but has not been widely adopted in the United States (US). It is standard to deliver radiotherapy by 3D planning, while the use of Intensity-modulated radiotherapy (IMRT) is controversial. In recent years there has been an increasing focus on understanding the cost and value of cancer care. In this study we aimed to assess the economic impact of fractionation scheme and treatment planning method for payers in the US. Methods: We performed a population-based analysis of the total cost of radiotherapy for LARC in the US annually. The national annual target population of patients was calculated using the Surveillance, Epidemiology, and End Results (SEER) database. Treatment costs for various fractionation schemes were based on billing codes and 2018 pricing by Medicare's Hospital Outpatient Prospective Payment System (OPPS). The cost of chemotherapy was based on the Payment Allowance Limits for Medicare Part B Drugs by Centers for Medicare and Medicaid Services (CMS). Results: We estimate that 12,945 patients with LARC are treated with radiotherapy annually in the US. The cost of CRT with 3-D or IMRT is US$ 15,881.76 and US$ 23,744.82 per patient, respectively. With 3-D SCR the cost is US$ 5,457 per patient. The use of SCR would lead to 64-77% annual savings of US$ 125,701,387 - US$ 236,727,934 in the US compared with 3-D and IMRT based CRT, respectively. IMRT based planning increases the total cost of CRT by 49% and if adopted widely would lead to an excess cost of US$ 101,787,312 annually. Conclusions: SCR may have the potential to save in the region of US$ 0.12-0.23 billion annually in the US, likely without impacting outcomes. Lack of evidence showing benefit with costly IMRT should limit its use to clinical trials. SCR may also lead to lower personal financial toxicity. It would be reasonable for public and private payers to consider which type of radiation is most suited to reimbursement.

Intensity-modulated radiotherapy (55 Gy in 20 fractions) for high-grade laryngeal dysplasia: report of acute toxicity and functional outcome.

Radiotherapy is an option to treat high-grade laryngeal dysplasia. This study aimed to evaluate the use of intensity-modulated radiotherapy, 55 Gy in 20 daily fractions, in treating this disease. Acute toxicity was evaluated in all 14 patients treated. In 10 patients, functional voice outcome was measured using the Voice Handicap Index, and the Grade, Roughness, Breath, Asthenia, Strain ('GRBAS') scale. These measurements were performed pre-treatment and three months after intensity-modulated radiotherapy. All but one patient managed to complete radiotherapy. Acute toxicity was significant (one patient developed grade 4 and three patients developed grade 3 dysphagia). Four patients required hospital admission. In 9 out of 10 patients, radiotherapy improved voice quality. This radiotherapy regimen using intensity-modulated radiotherapy for laryngeal dysplasia is feasible and provided excellent functional outcome, but acute toxicity was significant. Dose de-escalation can be considered in the framework of clinical trials.

Technical Advances in Radiation Therapy for Brain Tumors.

Radiation therapy plays a critical role in the management of brain tumors. Recent advances in radiation techniques include the use of intensity-modulated radiotherapy (IMRT), volumetric-modulated arc therapy (VMAT) and stereotactic radiosurgery (SRS). All of these techniques allow the delivery of higher radiation doses to the target volume, at the same time reducing the risk of toxicity to normal tissues as compared with conventional 3D conformal radiotherapy (3D-CRT). Proton therapy may represent a treatment alternative to photon irradiation, due to the more favorable dose distribution to the target volume. This review summarizes current developments in radiation therapy and their clinical impact on the management of patients with brain tumors.

Association of Target Volume Margins With Locoregional Control and Acute Toxicities for Non-small cell lung cancer Treated With Concurrent Chemoradiation Therapy

PurposeThis study aimed to investigate the association between target volume margins and clinical outcomes for patients with inoperable non-small cell lung cancer (NSCLC) treated with concurrent chemoradiation therapy. Methods and materialsWe reviewed the records of 82 patients with inoperable NSCLC treated between 2009 and 2016 with concurrent chemoradiation. All patients received positron emission tomography–based treatment planning, 4-dimensional computed tomography simulation to define an internal target volume, and daily cone beam computed tomography. We quantified variations in target volume margins with a margin deviation index (MDI), calculated as the percentage change in equivalent uniform dose between the original planning target volume (PTV) and a standard reference PTV 10 mm beyond the original gross tumor volume, consistent with the minimum margins mandated by recent NSCLC trials. Greater MDIs equated to smaller effective target volume margins. We dichotomized patients by the upper tercile MDI value (5.8%). Endpoints included time to locoregional progression and time to grade ≥ 3 radiation esophagitis (RE3) or radiation pneumonitis (RP3), modelled with the Fine-Gray method. ResultsMedian follow-up was 37.8 months (range, 5.9-58.1 months). Larger MDIs correlated with smaller clinical target volume (CTV) + PTV margins, larger gross tumor volumes, later treatment year, and intensity modulated radiation therapy use. The risk of locoregional progression did not differ for MDI ≥5.8% versus <5.8% (adjusted hazard ratio: 0.88; P = .76), but the risk of RE3 or RP3 was decreased for MDI ≥5.8% (adjusted hazard ratio: 0.27; P = .027). Patients with MDI ≥5.8% were treated with smaller CTV + PTV margins (median, 5.6 vs 8 mm; P < .0001) and a marginally lower volume of esophagus receiving ≥50 Gy (median, 31.1% vs 35.3%; P = .069). ConclusionsSmaller margins were used for larger tumors but were not associated with an increase in locoregional failures. Additional studies could clarify whether smaller margins, when used alongside modern radiation therapy techniques, decrease treatment-related toxicity for inoperable NSCLC.