National practice patterns of proton versus photon therapy in the treatment of adult patients with primary brain tumors in the United States.

OBJECTIVES: To examine patterns of care associated with the administration of proton versus photon therapy for adult patients with primary brain tumors in a large national cohort from the United States. METHODS: The National Cancer Database (NCDB) was queried for newly diagnosed primary brain tumors (2004-2014) in adult patients aged 18 and older receiving proton or photon radiotherapy. Clinical features, patient demographics and treatment parameters were extracted. Differences between groups were assessed using multivariable logistic regression analysis. RESULTS: In total, 73,073 patients were analyzed (n = 72,635 [99.4%] photon therapy, n = 438 [0.6%] proton therapy). On multivariable analysis of photon versus proton therapy, several factors predicted for receipt of proton therapy, including younger age (p = .041), highest income quartile (p = .007), treatment at academic institutions (p < .001), in regional facilities outside the Midwest/South (p < .001), diagnosis in more recent years (p = .003), fewer comorbidities (p < .001) and non-glioblastoma histology (p < .001). CONCLUSIONS: There are several significant socioeconomic variables that influence receipt of proton therapy for primary brain tumors. Although not implying causation, the socioeconomic findings discovered herein should be taken into account when delivering cancer care to all patients.

Patterns of care and outcomes with the addition of chemotherapy to radiation therapy for stage I nasopharyngeal cancer.

PURPOSE: The standard of care for stage I (T1N0) nasopharyngeal cancer (NPC) is definitive radiotherapy (RT). Given the phase III evidence supporting combined chemoradiotherapy (CRT) for stage II NPC, we investigated practice patterns and outcomes associated with administration of chemotherapy to RT alone for stage I NPC. METHODS: The National Cancer Data Base (NCDB) was queried for clinical T1N0 primary NPC cases (2004-2013) receiving curative-intent RT. Patients with unknown RT/chemotherapy status were excluded, as were benign/sarcomatous histologies and receipt of pharyngectomy. Patient, tumor, and treatment parameters were extracted. Logistic regression analysis ascertained factors associated with receipt of additional chemotherapy. Kaplan-Meier analysis was used to evaluate overall survival (OS) between patients receiving RT versus CRT. Cox proportional hazards modeling determined variables associated with receipt of OS. RESULTS: In total, 396 patients were analyzed. Chemotherapy was delivered in 147 patients (37%). On multivariate analysis, patients treated at academic/integrated centers were less likely to receive chemotherapy (p = .008); a racial predilection was noted, as non-black/non-white patients were also less likely to receive chemotherapy (p = .006). Respective 5-year OS in patients receiving RT alone versus CRT were 77% and 75% (p = .428). Receipt of chemotherapy did not independently predict for greater OS (p = .447). CONCLUSIONS: These data do not support the routine addition of chemotherapy to definitive RT for T1N0 NPC.

Patterns of Care for Stage IA Cervical Cancer: Use of Definitive Radiation Therapy Versus Hysterectomy.

OBJECTIVE: The standard of care for clinical IA cervical cancer is surgery, but nonoperative cases may receive definitive radiation therapy (RT). Herein, we investigated national practice patterns associated with the administration of definitive RT as compared with hysterectomy-based surgery (HYS) as well as delivery of adjuvant RT after HYS. METHODS/MATERIALS: The National Cancer Data Base (NCDB) was queried for clinical IA primary cervical cancer cases (2004-2013) receiving definitive RT or HYS with or without adjuvant RT. Patients with unknown RT or surgery status were excluded, as were benign histologies and receipt of non-HYS such as fertility-sparing surgery. Patient, tumor, and treatment parameters were extracted. Univariable and multivariable logistic regression determined variables associated with receipt of RT and HYS. RESULTS: In total, 3816 patients were analyzed (n = 3514 [92.1%] HYS alone, n = 100 [2.6%] RT alone, n = 202 [5.3%] combination). On multivariable analysis of HYS versus definitive RT, RT was more likely to be given to patients who were older (P < 0.001) and with Medicare (P = 0.011), Medicaid/other government insurance (P = 0.011), or uninsured/unknown status (P = 0.003). In addition, treatment with surgery alone was associated with patients in the 2 highest income quartiles (P = 0.013, P = 0.054). On multivariable analysis of patients receiving RT in addition to HYS, adjuvant RT was added most commonly for positive margins (P < 0.001) and increasing age (P < 0.001). CONCLUSIONS: This is the largest analysis to date evaluating definitive RT for IA cervical cancer. Younger age and higher socioeconomic status are associated with receipt of HYS instead of definitive RT, and positive margins are most associated with the addition of adjuvant RT. Although these data must be further validated with better defined patient selection and do not imply causation, several socioeconomic findings discovered herein need to be addressed to ensure the highest quality cancer care to all patients.

Open RT Structures: A Solution for TG-263 Accessibility.

PURPOSE: Consistency of nomenclature within radiation oncology is increasingly important as big data efforts and data sharing become more feasible. Automation of radiation oncology workflows depends on standardized contour nomenclature that enables toxicity and outcomes research, while also reducing medical errors and facilitating quality improvement activities. Recommendations for standardized nomenclature have been published in the American Association of Physicists in Medicine (AAPM) report from Task Group 263 (TG-263). Transitioning to TG-263 requires creation and management of structure template libraries and retraining of staff, which can be a considerable burden on clinical resources. Our aim is to develop a program that allows users to create TG-263-compliant structure templates in English, Spanish, or French to facilitate data sharing. METHODS AND MATERIALS: Fifty-three premade structure templates were arranged by treated organ based on an American Society for Radiation Oncology (ASTRO) consensus paper. Templates were further customized with common target structures, relevant organs at risk (OARs) (eg, spleen for anatomically relevant sites such as the gastroesophageal junction or stomach), subsite- specific templates (eg, partial breast, whole breast, intact prostate, postoperative prostate, etc) and brachytherapy templates. An informal consensus on OAR and target coloration was also achieved, although color selections are fully customizable within the program. RESULTS: The resulting program is usable on any Windows system and generates template files in practice-specific Digital Imaging and Communications In Medicine (DICOM) or XML formats, extracting standardized structure nomenclature from an online database maintained by members of the TG-263U1, which ensures continuous access to up-to-date templates. CONCLUSIONS: We have developed a tool to easily create and name DICOM radiation therapy (DICOM-RT) structures sets that are TG-263-compliant for all planning systems using the DICOM standard. The program and source code are publicly available via GitHub to encourage feedback from community users for improvement and guide further development.

Safety of Radiation Therapy in Patients With Prostate Cancer and Inflammatory Bowel Disease: A Systematic Review.

PURPOSE: Inflammatory bowel disease (IBD) has historically been considered a relative contraindication for pelvic radiation therapy (RT). To date, no systematic review has summarized the toxicity profile of RT for patients with prostate cancer and comorbid IBD. METHODS AND MATERIALS: A PRISMA-guided systematic search was conducted on PubMed/Embase for original investigations that reported gastrointestinal (GI; rectal/bowel) toxicity in patients with IBD undergoing RT for prostate cancer. The substantial heterogeneity in patient population, follow-up, and toxicity reporting practices precluded a formal meta-analysis; however, a summary of the individual study-level data and crude pooled rates was described. RESULTS: Twelve retrospective studies with 194 patients were included: 5 examined predominantly low-dose-rate brachytherapy (BT) monotherapy, 1 predominantly high-dose-rate BT monotherapy, 3 mixed external beam RT (3-dimensional conformal or intensity modulated RT [IMRT]) + low-dose-rate BT, 1 IMRT + high-dose-rate BT, and 2 stereotactic RT. Among these studies, patients with active IBD, patients receiving pelvic RT, and patients with prior abdominopelvic surgery were underrepresented. In all but 1 publication, the rate of late grade 3+ GI toxicities was <5%. The crude pooled rate of acute and late grade 2+ GI events was 15.3% (n = 27/177 evaluable patients; range, 0%-100%) and 11.3% (n = 20/177 evaluable patients; range, 0%-38.5%), respectively. Crude rates of acute and late grade 3+ GI events were 3.4% (6 cases; range, 0%-23%) and 2.3% (4 cases; range, 0%-15%). CONCLUSIONS: Prostate RT in patients with comorbid IBD appears to be associated with low rates of grade 3+ GI toxicity; however, patients must be counseled regarding the possibility for lower-grade toxicities. These data cannot be generalized to the underrepresented subpopulations mentioned above, and individualize decision-making is recommended for those high-risk cases. Several strategies should be considered to minimize the probability of toxicity in this susceptible population, including careful patient selection, minimizing elective (nodal) treatment volumes, using rectal sparing techniques, and employing contemporary RT advancements to minimize exposure to GI organs at risk (eg, IMRT, magnetic resonance imaging-based target delineation, and high-quality daily image guidance).

American Society of Clinical Oncology 2022 Annual Meeting Highlights for Radiation Oncologists.

The American Society of Clinical Oncology annual meeting is the largest multidisciplinary oncology-focused conference in the world. With almost 5000 total abstracts in 2022, it is difficult for individuals to evaluate all the results. Here we present a review of 28 selected abstracts, across all disease sites, focusing on those of greatest relevance to radiation oncologists.

Local Treatment of the Primary Tumor for Patients With Metastatic Cancer (PRIME-TX): A Meta-Analysis.

PURPOSE: Local treatment of the primary tumor for patients with metastases is controversial, and prospective data across many disease sites have conflicting conclusions regarding benefits. METHODS AND MATERIALS: A comprehensive search was conducted in PubMed/MEDLINE including randomized controlled trials (RCTs) published in the past 50 years. Inclusion criteria were multi-institutional RCTs of patients with metastatic disease receiving systemic therapy randomized to addition of local treatment to the primary tumor. Two primary outcome measures, overall survival (OS) and progression-free survival (PFS), were quantitatively assessed using random effects, and meta-analyses were conducted using the inverse variance method for pooling. Secondary endpoints were qualitatively assessed and included toxicity and patient-reported quality of life. Exploratory analyses were performed by treatment type and volume of disease. RESULTS: Eleven studies comprising 4952 patients were included (1558 patients received radiation therapy and 913 patients received surgery as primary tumor treatment). OS and PFS were not significantly improved from treatment of the primary (OS: hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.80-1.05; PFS: HR, 0.88; 95% CI, 0.72-1.07). Assessment of primary local treatment modality demonstrated a significant difference in summary effect size on PFS between trials using surgery (HR, 1.15; 95% CI, 0.99-1.33) compared with radiation therapy (HR, 0.73; 95% CI, 0.56-0.96) as the local treatment modality (P = .005). In low metastatic burden patients, radiation therapy was associated with significantly improved OS (HR, 0.67; 95% CI, 0.52-0.85), but surgery was not associated with improved OS compared with no local treatment (HR, 1.12; 95% CI, 0.94-1.34). CONCLUSIONS: In RCTs conducted to date enrolling a variety of cancer types with variable metastatic burden, there is no consistent improvement in PFS or OS from the addition of local therapy to the primary tumor in unselected patients with metastatic disease. Carefully selected patients may derive oncologic benefit and should be discussed in tumor boards. Future prospective studies should aim to further optimize patient selection and the optimal systemic and local therapy treatment types.

The timing and design of stereotactic radiotherapy approaches as a part of neoadjuvant therapy in pancreatic cancer: Is it time for change?

Stereotactic Radiotherapy (SRT) over 5-15 days can be interdigitated without delaying chemotherapy. Bridging chemotherapy may allow for extended intervals to surgery, potentially improving sterilization of surgical margins and overall survival. SRT for pancreatic adenocarcinoma should not be limited to the tumor, and should consider hypofractionated approaches to regional nodes.

Stereotactic body radiation therapy mitigates radiation induced lymphopenia in early stage non-small cell lung cancer.

INTRODUCTION: Radiation-induced lymphopenia (RIL) occurs during treatment with conventional radiation in multiple organ sites. Development of RIL portends poor prognosis. Stereotactic body radiation therapy (SBRT) spares RIL in pancreatic cancer, but has not been examined in other sites commonly treated with SBRT. This work examines if SBRT similarly spares RIL in patients with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Retrospective analysis was done at a single institution on 40 distinct cases of SBRT for early stage NSCLC from 2006-2017. Incidentally collected lymphocyte counts collected within 6 months of SBRT treatment were analyzed to determine if RIL occurred. The presence of RIL was correlated with location of initial failure and survival endpoints. Kaplan-Meier curves were constructed with significance defined at the level p < 0.05. RESULTS: RIL was observed in 35% of the analyzed patients. Patterns of failure and survival data were comparable to prior SBRT literature. There was no observed association in two year local, nodal, or distant failure, progression free survival, or overall survival based on the presence of RIL. DISCUSSION: SBRT spares RIL in NSCLC compared to historical rates observed with conventionally fractionated radiation. As understanding of the role of the immune system in cancer control continues to evolve, the importance of RIL sparing techniques take on increasing importance. This study represents further analysis of RIL sparing in SBRT in an early stage NSCLC cohort without the confounding influence of chemotherapy.

Correlation of dosimetric factors with the development of symptomatic radiation pneumonitis in stereotactic body radiotherapy.

BACKGROUND: The development of radiation pneumonitis (RP) after Stereotactic Body Radiotherapy (SBRT) is known to be associated with many different factors, although historical analyses of RP have commonly utilized heterogeneous fractionation schemes and methods of reporting. This study aims to correlate dosimetric values and their association with the development of Symptomatic RP according to recent reporting standards as recommended by the American Association of Physicists in Medicine. METHODS: We performed a single-institution retrospective review for patients who received SBRT to the lung from 2010 to 2017. Inclusion criteria required near-homogeneous tumoricidal (α/ß = 10 Gy) biological effective dose (BED10) of 100-105 Gy (e.g., 50/5, 48/4, 60/8), one or two synchronously treated lesions, and at least 6 months of follow up or documented evidence of pneumonitis. Symptomatic RP was determined clinically by treating radiation oncologists, requiring radiographic evidence and the administration of steroids. Dosimetric parameters and patient factors were recorded. Lung volumes subtracted gross tumor volume(s). Wilcoxon Rank Sums tests were used for nonparametric comparison of dosimetric data between patients with and without RP; p-values were Bonferroni adjusted when applicable. Logistic regressions were conducted to predict probabilities of symptomatic RP using univariable models for each radiation dosimetric parameter. RESULTS: The final cohort included 103 treated lesions in 93 patients, eight of whom developed symptomatic RP (n = 8; 8.6%). The use of total mean lung dose (MLD) > 6 Gy alone captured five of the eight patients who developed symptomatic RP, while V20 > 10% captured two patients, both of whom demonstrated a MLD > 6 Gy. The remaining three patients who developed symptomatic RP without exceeding either metric were noted to have imaging evidence of moderate interstitial lung disease, inflammation of the lungs from recent concurrent chemoradiation therapy to the contralateral lung, or unique peri-tumoral inflammatory appearance at baseline before treatment. CONCLUSIONS: This study is the largest dosimetric analysis of symptomatic RP in the literature, of which we are aware, that utilizes near-homogenous tumoricidal BED fractionation schemes. Mean lung dose and V20 are the most consistently reported of the various dosimetric parameters associated with symptomatic RP. MLD should be considered alongside V20 in the treatment planning process. TRIAL REGISTRATION: Retrospectively registered on IRB 398-17-EP.

Concurrent Versus Sequential Chemoradiation for Low-grade Gliomas Meeting RTOG 9802 Criteria.

PURPOSE: Radiation Therapy Oncology Group (RTOG) 9802 has established postoperative radiation therapy (RT) and chemotherapy sequentially as the new standard of care for patients with high-risk low-grade glioma (LGG) meeting trial criteria. Although this trial investigated sequential chemoradiation therapy (sCRT) with RT followed by chemotherapy, it is unknown whether concurrent chemoradiation therapy (cCRT) may offer advantages over sCRT. MATERIALS AND METHODS: The National Cancer Database (NCDB) was queried for newly diagnosed World Health Organization (WHO) grade II glioma. Patients with unknown surgery, RT, or chemotherapy status were excluded, along with patients below 40 years old who underwent gross total resection to coincide with RTOG 9802 exclusion criteria. The χ, the Fisher exact, or Wilcoxon rank-sum tests evaluated differences in characteristics between groups. Kaplan-Meier analysis was used to evaluate overall survival (OS) between groups (sCRT vs. cCRT). Cox proportional hazards modeling determined variables associated with OS. RESULTS: In total, 496 patients were analyzed (n=416 [83.9%] cCRT, n=80 [16.1%] sCRT). Sequencing or concurrency of therapy did not independently influence survival on univariable/multivariable analysis. Factors associated with worse OS on multivariable analysis included advanced age (P<0.001), whereas mixed glioma (P=0.017) and oligodendroglioma (P=0.005) were associated with better OS than astrocytoma histologies. CONCLUSIONS: This is the only analysis of which we are aware of cCRT versus sCRT for LGG. There is no evidence that cCRT improves outcomes over sCRT.

Sequencing of Chemotherapy and Radiotherapy for Newly Diagnosed Anaplastic Oligodendroglioma and Oligoastrocytoma.

INTRODUCTION: Adjuvant management of anaplastic oligodendrogliomas (AOs) and anaplastic oligoastrocytomas (AOAs) is guided by 2 seminal phase III trials, one of which utilized radiotherapy (RT) followed by chemotherapy (CT) (RT-CT), and the other in which CT was followed by RT (CT-RT). Both paradigms are endorsed by the National Comprehensive Cancer Network because no direct comparison in the first-line (nonprogressive) setting has been performed to date. This study of a contemporary national database sought to evaluate practice patterns and outcomes between both approaches. MATERIALS AND METHODS: The National Cancer Database (NCDB) was queried for newly diagnosed AO/AOA treated with postoperative sequential CT-RT or RT-CT. Multivariable logistic regression ascertained factors independently associated with delivery of a particular paradigm. Overall survival (OS) between cohorts was compared using Kaplan-Meier methodology. Univariate and multivariate Cox proportional hazards modeling evaluated factors associated with OS. RESULTS: Of 225 patients, 19 (8.4%) received CT-RT and 206 (91.6%) underwent RT-CT. Groups were well-balanced, although CT-RT was more often administered to men (P=0.009) and AOs (P=0.037). Median follow-up was 58 months. Median OS in the CT-RT cohort was 93 months (95% confidence interval, 37-150 mo), and 107 months (95% confidence interval, 72-142 mo) in the RT-CT group (P=0.709). Therapy sequence was not associated with OS on univariate (P=0.709) or multivariate (P=0.257) assessment. CONCLUSIONS: In the United States, most AO/AOA patients receiving sequential therapy undergo RT followed by CT. No differences in survival were observed with either approach; this addresses a knowledge gap and confirms that both paradigms are appropriate in the first-line setting.

Radiomic feature stability across 4D respiratory phases and its impact on lung tumor prognosis prediction.

Radiomic analysis has recently demonstrated versatile uses in improving diagnostic and prognostic prediction accuracy for lung cancer. However, since lung tumors are subject to substantial motion due to respiration, the stability of radiomic features over the respiratory cycle of the patient needs to be investigated to better evaluate the robustness of the inter-patient feature variability for clinical applications, and its impact in such applications needs to be assessed. A full panel of 841 radiomic features, including tumor intensity, shape, texture, and wavelet features, were extracted from individual phases of a four-dimensional (4D) computed tomography on 20 early-stage non-small-cell lung cancer (NSCLC) patients. The stability of each radiomic feature was assessed across different phase images of the same patient using the coefficient of variation (COV). The relationship between individual COVs and tumor motion magnitude was inspected. Population COVs, the mean COVs of all 20 patients, were used to evaluate feature motion stability and categorize the radiomic features into 4 different groups. The two extremes, the Very Small group (COV≤5%) and the Large group (COV>20%), each accounted for about a quarter of the features. Shape features were the most stable, with COV≤10% for all features. A clinical study was subsequently conducted using 140 early-stage NSCLC patients. Radiomic features were employed to predict the overall survival with a 500-round bootstrapping. Identical multiple regression model development process was applied, and the model performance was compared between models with and without a feature pre-selection step based on 4D COV to pre-exclude unstable features. Among the systematically tested cutoff values, feature pre-selection with 4D COV≤5% achieved the optimal model performance. The resulting 3-feature radiomic model significantly outperformed its counterpart with no 4D COV pre-selection, with P = 2.16x10-27 in the one-tailed t-test comparing the prediction performances of the two models.

National Cancer Database report of nonmetastatic esophageal small cell carcinoma.

BACKGROUND: Esophageal small cell carcinoma (ESCC) is a rare malignancy for which there is no consensus management approach. This is the largest known analysis of nonmetastatic ESCC patients to date, evaluating national practice patterns and outcomes of surgical-based therapy vs chemoradiotherapy (CRT) vs chemotherapy alone. METHODS: The National Cancer Data Base was queried for esophageal cancer patients with histologically confirmed nonmetastatic ESCC. Univariable and multivariable logistic regression ascertained factors associated with receipt of surgical-based management. Kaplan-Meier analysis evaluated overall survival (OS) and the log-rank test is used to compare OS between groups; Cox univariate and multivariate analyses determined variables associated with OS. RESULTS: Altogether, 323 patients were analyzed; 64 (20%) patients underwent surgical-based therapy, 211 (65%) CRT, and 48 (15%) chemotherapy alone. On multivariable analysis, no single factor significantly predicted for administration of surgery. Despite no OS differences between the surgery-based (median OS 21 months) and CRT arms (18 months), both were superior to CT alone (10 months) (P < 0.001). Among other factors, receiving any local therapy independently predicted for higher OS over chemotherapy alone on Cox multivariate analysis (P < 0.001). CONCLUSIONS: This study of a large, contemporary national database demonstrates that most ESCC is treated with CRT in the United States; adding local therapy to systemic therapy may be beneficial to these patients, although individualized multidisciplinary management is still recommended.

Anatomic structure-based deformable image registration of brachytherapy implants in the treatment of locally advanced cervix cancer.

PURPOSE: To examine the impact of anatomic structure-based image sets in deformable image registration (DIR) for cervical cancer patients. METHODS AND MATERIALS: CT examinations of 7 patients previously treated for locally advanced cervical cancer with external beam radiation therapy and from three to five fractions of high-dose-rate brachytherapy (HDR-BT) were used. Structure-based image sets were created from "free" structures already made for planning purposes, with each structure of interest assigned a unique, homogeneous Hounsfield number. Subsequent HDR fractions were registered to the pretreatment external beam radiation therapy and/or the first HDR fraction using commercially available software by rigid alignment (RIG) followed by DIR. Comparison methods included quantification of external contour displacement between source and target images and calculation of mean voxel displacement values. Registration results for structure-based image sets were then compared and contrasted to intensity-based registrations of the original grayscale images. RESULTS: Utilization of anatomic structure-based image sets resulted in better initial rigid matching (A-RIG) with more importance on applicator positioning and soft tissue structures. Subsequent DIR of anatomic structure-based images allowed for intermodality registrations, whereas all intermodality registrations using original CT images failed to produce anatomically feasible results. CONCLUSIONS: We have investigated the use of structure-based CT image sets for image registrations and have produced anatomically favorable registrations with excellent matching of external contours as compared to registrations of original grayscale images. Commercial software registrations using treatment-planning structures required no manual tweaking on a per-patient basis, suggesting results are reproducible and broadly applicable.