Characterizing impact of positive lymph node number in endometrial cancer using machine-learning: A better prognostic indicator than FIGO staging?

BACKGROUND: Number of involved lymph nodes (LNs) is a crucial stratification factor in staging of numerous disease sites, but has not been incorporated for endometrial cancer. We evaluated whether number of involved LNs provide improved prognostic value. PATIENTS AND METHODS: Patients diagnosed with node-positive endometrial adenocarcinoma without distant metastasis were identified in the National Cancer Database. We trained a machine-learning based model of overall survival. Shapley additive explanation values (SHAP) based on the model were used to identify cutoffs of number of LNs involved. Results were validated using a Cox proportional hazards regression model. RESULTS: We identified 11,381 patients with endometrial cancer meeting the inclusion criteria. Using the SHAP values, we selected the following thresholds: 1-3 LNs, 4-5 LNs, and 6+ LNs. The 3-year OS was 82.0% for 1-3 LNs, 74.3% for 4-5 LNs (hazard ratio [HR] 1.38; p < 0.001), and 59.9% for 6+ LNs (HR 2.23; p < 0.001). On univariate Cox regression, PA nodal involvement was a significant predictor of OS (HR 1.20; p < 0.001) but was not significant on multivariate analysis when number of LNs was included (HR 1.05; p = 0.273). Additionally, we identified an interaction between adjuvant therapy and number of involved LNs. Patients with 1-3 involved LNs had 3-year OS of 85.2%, 78.7% and 74.2% with chemoradiation (CRT), chemotherapy, and radiation, respectively. Patients with 6+ involved LNs had 3-yr OS of 67.8%, 49.6%, and 48.9% with CRT, chemotherapy, and radiation, respectively (p < 0.001). CONCLUSION: Number of involved LNs is a stronger prognostic and predictive factor compared to PA node involvement.

Stereotactic Body Radiation Therapy, Intensity-Modulated Radiation Therapy, and Brachytherapy Boost Modalities in Invasive Cervical Cancer: A Study of the National Cancer Data Base.

BACKGROUND AND PURPOSE: Our objective was to determine whether stereotactic body radiotherapy (SBRT), intensity-modulated radiation therapy (IMRT), and brachytherapy boost techniques have comparable overall survival in treating cervical cancer when adjusted for known prognostic factors. MATERIALS AND METHODS: We used the National Cancer Database to study women with invasive cervical cancer who were treated with radiation between 2004 and 2013. A logistic regression model was built to identify factors associated with the receipt of SBRT and IMRT. Outcomes were compared using Kaplan-Meier and propensity score matching. RESULTS: Of all 15,905 patients, 14,394 (90.5%) received brachytherapy, 42 (0.8%) received SBRT, and 1468 (9.2%) received IMRT. After propensity score matching, there was no significant difference in overall survival (OS) for patients who received SBRT boost versus brachytherapy boost (hazard ratio = 1.477, 95% confidence interval = 0.746-2.926, P = 0.263) but a significant OS detriment in patients who received IMRT boost versus brachytherapy boost (hazard ratio = 1.455, 95% confidence interval = 1.300-1.628, P < 0.001). CONCLUSIONS: In a propensity-matched analysis, those who received SBRT boost had equal OS when compared with brachytherapy, but those who received IMRT boost had worse OS when compared with brachytherapy.

Contemporary Role of Radiation Therapy in Testicular Cancer.

Testicular cancer is a rare but curable male malignancy. Seminoma represents the majority of germ cell tumors and is considered radiation sensitive. Radiation treatment plays a role in adjuvant therapy after orchiectomy of stage I, IIA, and IIB seminomas. Radiation dose de-escalation has been effective in preventing tumor recurrences while also limiting acute and long-term toxicities. However, long-term risks, including the prevailing concern of secondary malignancy risk, between adjuvant radiation and chemotherapy play a role in recommendations. Ongoing work continues to be performed to reduce radiation field and dose in combination with chemotherapy while still maintaining excellent outcomes.

Pilot Curriculum for Continued Professional Development of Radiation Oncology Nurses.

Purpose: Limited structured educational programs are available for the continued professional development of radiation oncology nurses. In this study, we evaluated a pilot curriculum focusing on clinical workflow and toxicity management for radiation oncology nurses at a single university-affiliated medical center network. Methods and Materials: Based on a previous multi-institutional needs assessment, a targeted curriculum on clinical workflow and toxicity management was developed, including didactic lectures, written disease-specific toxicity management guidelines, and standardized medication/laboratory order preference lists in the electronic health record. An anonymized survey was circulated to all participants pre- and postcurriculum. The survey was composed of Likert-type subjective questions and 11 objective knowledge-based questions (KBQs). Paired Likert-type data were analyzed using Wilcoxon signed ranks test. Objective question data were compared with the McNamar's mid P test. Results: Thirteen nurses participated in the pilot curriculum and 100% completed pre- and post curriculum surveys. After the didactics, nurses reported a significant increase in their understanding of the responsibilities of a nurse and overall process of care and their ability to explain computed tomography simulation, as well as their ability to assess, manage, and grade radiation-related toxicities (P < .01). There was significant improvement in the percent of correct answers on objective KBQs from a baseline of 52% to 80% after the curriculum (P < .01). Qualitatively, 70% (9/13) of nurses rated the curriculum as "extremely useful" and 30% (4/13) as "quite useful." Conclusions: Our pilot curriculum using a combination of in-person formal didactics, toxicity management guidelines, and electronic health record based order preference lists was well-received and showed promising results on KBQ assessment. This work may be used to guide the development of larger curricula for nurse onboarding and continuing education in a multicenter setting.

Detection of Alteration in Carotid Artery Volumetry Using Standard-of-care Computed Tomography Surveillance Scans Following Unilateral Radiation Therapy for Early-stage Tonsillar Squamous Cell Carcinoma Survivors: A Cross-Sectional Internally-Matched Carotid Isodose Analysis.

Purpose: Radiation induced carotid artery disease (RICAD) is a major cause of morbidity and mortality among survivors of oropharyngeal cancer. This study leveraged standard-of-care CT scans to detect volumetric changes in the carotid arteries of patients receiving unilateral radiotherapy (RT) for early tonsillar cancer, and to determine dose-response relationship between RT and carotid volume changes, which could serve as an early imaging marker of RICAD. Methods and Materials: Disease-free cancer survivors (>3 months since therapy and age >18 years) treated with intensity modulated RT for early (T1-2, N0-2b) tonsillar cancer with pre- and post-therapy contrast-enhanced CT scans available were included. Patients treated with definitive surgery, bilateral RT, or additional RT before the post-RT CT scan were excluded. Pre- and post-treatment CTs were registered to the planning CT and dose grid. Isodose lines from treatment plans were projected onto both scans, facilitating the delineation of carotid artery subvolumes in 5 Gy increments (i.e. received 50-55 Gy, 55-60 Gy, etc.). The percent-change in sub-volumes across each dose range was statistically examined using the Wilcoxon rank-sum test. Results: Among 46 patients analyzed, 72% received RT alone, 24% induction chemotherapy followed by RT, and 4% concurrent chemoradiation. The median interval from RT completion to the latest, post-RT CT scan was 43 months (IQR 32-57). A decrease in the volume of the irradiated carotid artery was observed in 78% of patients, while there was a statistically significant difference in mean %-change (±SD) between the total irradiated and spared carotid volumes (7.0±9.0 vs. +3.5±7.2, respectively, p<.0001). However, no significant dose-response trend was observed in the carotid artery volume change withing 5 Gy ranges (mean %-changes (±SD) for the 50-55, 55-60, 60-65, and 65-70+ Gy ranges [irradiated minus spared]: -13.1±14.7, -9.8±14.9, -6.9±16.2, -11.7±11.1, respectively). Notably, two patients (4%) had a cerebrovascular accident (CVA), both occurring in patients with a greater decrease in carotid artery volume in the irradiated vs the spared side. Conclusions: Our data show that standard-of-care oncologic surveillance CT scans can effectively detect reductions in carotid volume following RT for oropharyngeal cancer. Changes were equivalent between studied dose ranges, denoting no further dose-response effect beyond 50 Gy. The clinical utility of carotid volume changes for risk stratification and CVA prediction warrants further evaluation.

Fiducial Markers Allow Accurate and Reproducible Delivery of Liver Stereotactic Body Radiation Therapy.

Fiducial markers are utilized for image guided radiotherapy (IGRT) alignment during the delivery of liver stereotactic body radiosurgery (SBRT). There are limited data demonstrating the impact of matching fiducials on the accuracy of liver SBRT. This study quantifies the benefit of fiducial-based alignment and improvements in inter-observer reliability. Nineteen patients with 24 liver lesions were treated with SBRT. Target localization was performed using fiducial markers on cone-beam computed tomography (CBCT). Each CBCT procedure was retrospectively realigned to match both the liver edge and fiducial markers. The shifts were recorded by seven independent observers. Inter-observer variability was analyzed by calculating the mean error and uncertainty for the set-up. The mean absolute Cartesian error observed from fiducial and liver edge-based alignment was 1.5 mm and 5.3 mm, respectively. The mean uncertainty from fiducial and liver edge-based alignment was 1.8 mm and 4.5 mm, respectively. An error of 5 mm or greater was observed 50% of the time when aligning to the liver surface versus 5% of the time when aligning to fiducial markers. Aligning to the liver edge significantly increased the error, resulting in increased shifts when compared to alignment to fiducials. Tumors of 3 cm or farther from the liver dome had higher mean errors when aligned without fiducials (4.8 cm vs. 4.4 cm, p = 0.003). Our data support the use of fiducial markers for safer and more accurate liver SBRT.

The role of concomitant chemoradiotherapy versus radiation alone in T1-3N0 HPV-positive and HPV-negative oropharyngeal squamous cell carcinoma.

OBJECTIVE: To evaluate the role of curative intent concurrent chemoradiation (CCRT) vs radiation (RT) alone for T1-T3N0 HPV-positive and HPV-negative oropharyngeal squamous cell cancer (OPSCC). METHODS: The NCDB was queried for patients diagnosed between 2010 and 2017 with cT1-3N0M0 OPSCC treated with definitive RT or CCRT. Univariable analysis (UVA) and multivariable analysis (MVA) Cox regression analysis was performed with OS as the endpoint. Propensity score matching (PSM) 1:1 was performed. Interaction test to assess heterogeneity of treatment effect. RESULTS: A total of 2830 patients were queried. On MVA, CCRT was associated with improved OS for T3N0 tumors (HR 0.49; 95% CI 0.39-0.63) but not for T1N0 (HR 1.43; 95% CI 0.99-2.07) and T2N0 (HR 0.92; 95% CI 0.75-1.13). For T3 patients, CCRT improved OS for HPV-negative (HR 0.43; 95% CI 0.31-0.59) and HPV-positive tumors (HR 0.39; 95% CI 0.25-0.61). After PSM, CCRT was not statistically different to RT for patients with T1-2N0 HPV-negative tumors (HR 1.10; 95% CI 0.85-1.43; p = 0.48) and T1-2N0 HPV-positive tumors (HR 1.15; 95% CI 0.79-1.68; p = 0.45). After PSM, CCRT improved OS compared to RT alone for patients with T3N0 HPV-negative (HR 0.43; 95% CI 0.31-0.59; p < 0.01) and HPV-positive tumors (HR 0.39; 95 %CI 0.25-0.61; p < 0.01). CONCLUSIONS: CCRT is associated with improved OS in HPV-positive and HPV-negative T3N0 OPSCC. RT alone vs. CCRT demonstrated similar OS for T1-T2N0 OPSCC for both HPV negative and HPV positive tumors.

The Kelowna template for combined intracavitary and interstitial brachytherapy for gynecologic malignancies: Design, application, treatment planning, dosimetric and treatment outcomes.

PURPOSE: We report the feasibility, experience, and early outcomes of the combined intracavitary and interstitial dedicated applicator using the Kelowna GYN template (Varian, Palo Alto, CA). METHODS AND MATERIALS: The Kelowna GYN template is CT compatible and used for the treatment of gynecologic cancers. In cases with patients that have an intact uterus, a modified applicator system using the Kelowna GYN template and a 3D printed adapter piece allows for compatibility with an intrautaerine tandem. RESULTS: We reviewed the treatment course of 23 patients comprising of 86 fractions of HDR treatment. Median D90 for cervical tumors (n = 7) was 82.4 Gy (range 77.7-92.6); for postoperative cervical tumors (n = 2) was 73.9 Gy (range 72.0-5.8); for vaginal tumors (n = 4) was 85.8 Gy (range 79.8-88.1); for recurrent endometrial (n = 10) was 86.9 Gy (range 74.8-103.2). Median EQD2 D2cc for bladder was 72.4 Gy (range 47.7-99.4), for rectum was 61.2 Gy (range 52.4-80.6), and for sigmoid colon of 50.5 Gy (44.3-66.9). At a median follow-up of 12 months, 2 patients had a local recurrence. Two patients had distant recurrence: one with carcinomatosis at 6 months, and one with pulmonary metastases at 3 months. No patients had late grade three toxicities. CONCLUSIONS: Our single institutional experience supports the use of the Kelowna template as a robust system as a combined IC-IS applicator resulting in versatile and reproducible implants for a variety of gynecologic malignancies.

Gynecologic interstitial brachytherapy curriculum using a low-cost phantom with ultrasound workshop and a treatment planning workshop is effective.

PURPOSE/OBJECTIVE(S): Standardized simulation training geared towards interstitial brachytherapy (IS BT) for gynecologic malignancies is lacking in radiation oncology resident education. We developed and implemented a curriculum for IS BT training with (1) lecture on equipment, workflow, and guidelines, (2) hands-on ultrasound-guided IS BT workshop, and (3) treatment planning workshop. METHODS AND MATERIAL: The cost in materials of each phantom was approximately $66. After a lecture, two alternating workshops were performed. The first session consisted of a hands-on ultrasound-guided IS BT workshop with one resident imaging the phantom with a transabdominal ultrasound probe and the other resident implanting the phantom with needles. A second session consisted of a hands-on treatment planning workshop using BrachyVision and an l-Q spreadsheet with the following objectives: coverage goal, meeting D2cc constraints, and minimizing V200. The primary outcome was improvement in knowledge assessed with Likert-style questions and objective knowledge-based questions (KBQs). RESULTS: Four of the seven medical residents that participated in this curriculum had prior IS BT experience. Residents reported significantly improved knowledge regarding gynecologic IS BT equipment and procedure, evaluating gynecologic anatomy using ultrasound, CT simulation, contouring, and plan review (overall median pre-session subjective score 2 (1) -(3) versus post-session score 4 (3) -(4, p < 0.01). Residents demonstrated improvement in answering KBQs correctly from 44% correct at baseline to 88% after completion of the curriculum (p < 0.01). All residents "Agree" and "Strongly Agree" the session was an effective learning experience. CONCLUSIONS: Residents participating in phantom training with an ultrasound curriculum and a treatment planning session is effective for improving knowledge and skills in IS BT for radiation oncology residents.

Graded Prognostic Assessment (GPA) for Patients With Lung Cancer and Brain Metastases: Initial Report of the Small Cell Lung Cancer GPA and Update of the Non-Small Cell Lung Cancer GPA Including the Effect of Programmed Death Ligand 1 and Other Prognostic Factors.

PURPOSE: Patients with lung cancer and brain metastases represent a markedly heterogeneous population. Accurate prognosis is essential to optimally individualize care. In prior publications, we described the graded prognostic assessment (GPA), but a GPA for patients with small cell lung cancer (SCLC) has never been reported, and in non-small cell lung cancer (NSCLC), the effect of programmed death ligand 1 (PD-L1) was unknown. The 3-fold purpose of this work is to provide the initial report of an SCLC GPA, to evaluate the effect of PD-L1 on survival in patients with NSCLC, and to update the Lung GPA accordingly. METHODS AND MATERIALS: A multivariable analysis of prognostic factors and treatments associated with survival was performed on 4183 patients with lung cancer (3002 adenocarcinoma, 611 nonadenocarcinoma, 570 SCLC) with newly diagnosed brain metastases between January 1, 2015, and December 31, 2020, using a multi-institutional retrospective database. Significant variables were used to update the Lung GPA. RESULTS: Overall median survival for lung adenocarcinoma, SCLC, and nonadenocarcinoma was 17, 10, and 8 months, respectively, but varied widely by GPA from 2 to 52 months. In SCLC, the significant prognostic factors were age, performance status, extracranial metastases, and number of brain metastases. In NSCLC, the distribution of molecular markers among patients with lung adenocarcinoma and known primary tumor molecular status revealed alterations/expression in PD-L1 50% to 100%, PD-L1 1% to 49%, epidermal growth factor receptor, and anaplastic lymphoma kinase in 32%, 31%, 30%, and 7%, respectively. Median survival of patients with lung adenocarcinoma and brain metastases with 0, 1% to 49%, and ≥50% PD-L1 expression was 17, 19, and 24 months, respectively (P < .01), confirming PD-L1 is a prognostic factor. Previously identified prognostic factors for NSCLC (epidermal growth factor receptor and anaplastic lymphoma kinase status, performance status, age, number of brain metastases, and extracranial metastases) were reaffirmed. These factors were incorporated into the updated Lung GPA with robust separation between subgroups for all histologies. CONCLUSIONS: Survival for patients with lung cancer and brain metastases has improved but varies widely. The initial report of a GPA for SCLC is presented. For patients with NSCLC-adenocarcinoma and brain metastases, PD-L1 is a newly identified significant prognostic factor, and the previously identified factors were reaffirmed. The updated indices establish unique criteria for SCLC, NSCLC-nonadenocarcinoma, and NSCLC-adenocarcinoma (incorporating PD-L1). The updated Lung GPA, available for free at brainmetgpa.com, provides an accurate tool to estimate survival, individualize treatment, and stratify clinical trials.

Improving the Pediatric Patient Experience During Radiation Therapy-A Children's Oncology Group Study.

PURPOSE: Treatment with radiation therapy (RT) can cause anxiety and distress for pediatric patients and their families. Radiation oncology teams have developed strategies to reduce the negative psychological impact. This survey study aimed to characterize these methods. METHODS AND MATERIALS: A 37-item questionnaire was sent to all radiation oncology members of the Children's Oncology Group to explore strategies to improve the pediatric patient experience. The Wilcoxon rank-sum test was used to assess factors associated with use of anesthesia for older children. RESULTS: Surveys were completed by 106 individuals from 84/210 institutions (40%). Respondents included 89 radiation oncologists and 17 supportive staff. Sixty-one percent of centers treated ≤50 children per year. Respondents described heterogenous interventions. The median age at which most children no longer required anesthesia was 6 years (range: ≤3 years to ≥8 years). Routine anesthesia use at an older age was associated with physicians' lack of awareness of these strategies (P = .04) and <10 years of pediatric radiation oncology experience (P = .04). Fifty-two percent of respondents reported anesthesia use added >45 minutes in the radiation oncology department daily. Twenty-six percent of respondents planned to implement new strategies, with 65% focusing on video-based distraction therapy and/or augmented reality/virtual reality. CONCLUSIONS: Many strategies are used to improve children's experience during RT. Lack of awareness of these interventions is a barrier to their implementation and is associated with increased anesthesia use. This study aims to disseminate these methods with the goal of raising awareness, facilitating implementation, and, ultimately, improving the experience of pediatric cancer patients and their caregivers.

Stereotactic radiosurgery for central neurocytomas: an international multicenter retrospective cohort study.

OBJECTIVE: Central neurocytomas (CNs) are uncommon intraventricular tumors, and their rarity renders the risk-to-benefit profile of stereotactic radiosurgery (SRS) unknown. The aim of this multicenter, retrospective cohort study was to evaluate the outcomes of SRS for CNs and identify predictive factors. METHODS: The authors retrospectively analyzed a cohort of patients with CNs treated with SRS at 10 centers between 1994 and 2018. Tumor recurrences were classified as local or distant. Adverse radiation effects (AREs) and the need for a CSF shunt were also evaluated. RESULTS: The study cohort comprised 60 patients (median age 30 years), 92% of whom had undergone prior resection or biopsy and 8% received their diagnosis based on imaging alone. The median tumor volume and margin dose were 5.9 cm3 and 13 Gy, respectively. After a median clinical follow-up of 61 months, post-SRS tumor recurrence occurred in 8 patients (13%). The 5- and 10-year local tumor control rates were 93% and 87%, respectively. The 5- and 10-year progression-free survival rates were 89% and 80%, respectively. AREs were observed in 4 patients (7%), but only 1 was symptomatic (2%). Two patients underwent post-SRS tumor resection (3%). Prior radiotherapy was a predictor of distant tumor recurrence (p = 0.044). Larger tumor volume was associated with pre-SRS shunt surgery (p = 0.022). CONCLUSIONS: Treatment of appropriately selected CNs with SRS achieves good tumor control rates with a reasonable complication profile. Distant tumor recurrence and dissemination were observed in a small proportion of patients, which underscores the importance of close post-SRS surveillance of CN patients. Patients with larger CNs are more likely to require shunt surgery before SRS.

Imaging-Genomic Study of Head and Neck Squamous Cell Carcinoma: Associations Between Radiomic Phenotypes and Genomic Mechanisms via Integration of The Cancer Genome Atlas and The Cancer Imaging Archive.

PURPOSE: Recent data suggest that imaging radiomic features of a tumor could be indicative of important genomic biomarkers. Understanding the relationship between radiomic and genomic features is important for basic cancer research and future patient care. We performed a comprehensive study to discover the imaginggenomic associations in head and neck squamous cell carcinoma (HNSCC) and explore the potential of predicting tumor genomic alternations using radiomic features. METHODS: Our retrospective study integrated whole-genome multiomics data from The Cancer Genome Atlas with matched computed tomography imaging data from The Cancer Imaging Archive for the same set of 126 patients with HNSCC. Linear regression and gene set enrichment analysis were used to identify statistically significant associations between radiomic imaging and genomic features. Random forest classifier was used to predict the status of two key HNSCC molecular biomarkers, human papillomavirus and disruptive TP53 mutation, on the basis of radiomic features. RESULTS: Widespread and statistically significant associations were discovered between genomic features (including microRNA expression, somatic mutations, and transcriptional activity, copy number variations, and promoter region DNA methylation changes of pathways) and radiomic features characterizing the size, shape, and texture of tumor. Prediction of human papillomavirus and TP53 mutation status using radiomic features achieved areas under the receiver operating characteristic curve of 0.71 and 0.641, respectively. CONCLUSION: Our exploratory study suggests that radiomic features are associated with genomic characteristics at multiple molecular layers in HNSCC and provides justification for continued development of radiomics as biomarkers for relevant genomic alterations in HNSCC.

Quantitative pretreatment CT volumetry: Association with oncologic outcomes in patients with T4a squamous carcinoma of the larynx.

BACKGROUND: The purpose of this study was to determine the impact of CT-determined pretreatment primary tumor volume on survival and disease control in T4a laryngeal squamous cell carcinoma (SCC). METHODS: We retrospectively reviewed 124 patients with T4a laryngeal cancer from 2000-2011. Tumor volume measurements were collected and correlated with outcomes. RESULTS: Five-year overall survival (OS) for patients with tumor volume ≥21 cm3 treated with larynx preservation (n = 26 of 41) was significantly inferior compared to <21 cm3 (42% vs 64%, respectively; P = .003). Five-year OS for patients with tumor volumes ≥21 cm3 in the cohort treated with total laryngectomy followed by radiotherapy (RT; n = 42 of 83) was not statistically significant when compared to <21 cm3 (50% vs 63%, respectively; P = .058). On multivariate analysis, tumor volume ≥21 cm3 was a significant independent correlate of worse disease-specific survival (DSS; P = .004), event-free survival (P = .005), recurrence-free survival (RFS; P = .04), noncancer cause-specific survival (P = .02), and OS (P = .0002). CONCLUSION: Pretreatment CT-based tumor volume is an independent prognostic factor of outcomes in T4a laryngeal cancer.