Radiotherapy For Carcinoma Research Articles

Definitive radiotherapy for nasopharyngeal carcinoma in Japan: analysis of cases in the National Head and Neck Cancer Registry from 2011 to 2014.

This study aimed to analyze the nationwide prognosis of patients with nasopharyngeal carcinoma who underwent definitive radiotherapy in Japan, utilizing the National Head and Neck Cancer Registry data. A total of 741 patients diagnosed with primary nasopharyngeal carcinoma were screened from 2011 to 2014. The inclusion criteria were histologically proven nasopharyngeal squamous cell carcinoma, receiving definitive radiotherapy, and no distant metastases. Patients with unclear prognoses or unknown staging were excluded. The primary endpoint was 5-year overall survival, and secondary endpoints were 5-year progression-free survival and survival by stage. A total of 457 patients met the inclusion criteria. The median age was 60years, and 80% were male. The proportions of patients with performance status 0, 1, 2 and 3 were 69, 10, 1 and 1%, respectively. Chemoradiotherapy was administered to 84.7%. Radiotherapy modalities were recorded only for 29 patients (three received intensity-modulated radiotherapy and 26 received two/three-dimensional radiotherapy). Of those included, 7.4, 24.7, 35.7, 24.5 and 7.7% had Stage I, II, III, IVA and IVB disease, respectively. The 5-year overall survival was 72.5% for all patients: 82.6, 86.6, 76.0, 51.4 and 66.5% for Stage I, II, III, IVA and IVB disease, respectively. The 5-year progression-free survival was 58.6%: 75.6, 66.8, 61.5, 43.7 and 46.5% for Stage I, II, III, IVA and IVB disease, respectively. This nationwide survey demonstrated favorable prognoses and provided valuable foundational data for similar future surveys to monitor the penetration of appropriate treatment and changes in clinical structures based on new evidence.

1576P Comparison of efficacy and safety of first-line systemic therapy combined with or without radiotherapy for stage IVb esophageal squamous cell carcinoma: A propensity score matching analysis

1576P Comparison of efficacy and safety of first-line systemic therapy combined with or without radiotherapy for stage IVb esophageal squamous cell carcinoma: A propensity score matching analysis

Evaluation of Volumetric Response Assessment from Stereotactic Ablative Radiotherapy (SABR) for Renal Cell Carcinoma (RCC).

SABR has recently been proven to be a safe, effective treatment for RCC. However, long term follow-up assessment can be challenging as traditional methods of assessment such as RECIST may not identify tumor response, and delayed responses to SABR are common. The purpose of this study was to quantify SABR response using volumetric changes from baseline throughout follow-up. We conducted a single-center retrospective study including all patients treated with SABR for RCC from 2013 to 2020. Patients were included if they had no metastatic disease, no resection after SABR, and had follow-up imaging available for at least 12 months following SABR. All available follow-up CT scans were collected and aligned, and tumors were contoured on all follow-up scans to measure volume and maximum linear dimension. Response to SABR was assessed by comparing tumor volume at follow-up to the initial tumor volume at the time of CT simulation. Twenty-four patients with 25 tumors were included. The dose was between 25Gy and 42Gy in 1-5 fractions; 64% of tumors received 35Gy in 5 fractions. Follow-up time was between 16 and 67 months; median follow-up was 32 months. A total of 164 follow-up scans were contoured. The relative volume and standard deviation (compared to baseline) at 3, 6, 9, 12, 24, 36, and 48 months was 0.76 (SD 0.22), 0.80 (SD 0.27), 0.76 (SD 0.32), 0.75 (SD 0.26), 0.61 (SD 0.33), 0.53 (SD 0.41), and 0.34 (SD 0.22) respectively. One tumor (4%) showed continued growth after SABR, while 24 of 25 tumors (96%) had durable volumetric response after SABR. Eighteen of 25 tumors (72%) decreased in volume on first follow-up scan and continued to shrink, while 6 of 25 tumors (24%) displayed growth after SABR (average 33% increase in volume) before shrinking below their initial volume. The median time to any volumetric response was 3.5 months (range 2-19 months). Nineteen tumors (76%) had 30% volumetric response. Median time to 30% volumetric response was 7 months (range 3-55 months). In contrast, 12 tumors (48%) had 30% decrease in maximum linear size, with median time to 30% linear response of 16 months (range 4-42 months). Thirteen tumors (52%) had 50% volumetric response; median time to 50% volumetric response was 11 months (range 4-37 months). Among tumors for which contrast-enhanced scans were available, 15 of 22 tumors (68%) displayed arterial enhancement at their most recent follow-up scan, at a median time of 24 months after SABR. SABR is a highly effective treatment for RCC, achieving durable local control in 96% of cases. Initial growth after SABR is common before volumetric response occurs. Volumetric response is more frequent and occurs earlier than decrease in maximum linear dimension, even with persistent arterial contrast enhancement following SABR.

Survival Outcomes and Factors Affecting Prognosis in Patients with Head and Neck Region Mucoepidermoid Carcinoma Treated with Adjuvant Radiotherapy

Aim: This study aims to ascertain the clinical and pathological factors linked to the outcomes of patients subjected to surgical intervention and postoperative radiotherapy for mucoepidermoid carcinoma (MEC) originating from both major and minor salivary glands in the head and neck region.
 Material and Method: In this retrospective review, medical records of 42 patients who underwent surgery and subsequent radiotherapy for localized MEC in the major and minor salivary glands of the head and neck were analyzed to identify clinicopathological determinants of overall survival. Secondary endpoints encompassed local-regional control, distant metastasis-free survival, and disease-free survival.
 Results: The median age of the patient cohort was 56 years, comprising 52.4% males and 47.6% females. The median follow-up period spanned 36 months, with a range of 6 to 88 months. All patients underwent curative surgery, followed by adjuvant radiotherapy. The 2-year and 5-year rates for overall survival (OS), local-regional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and disease-free survival (DFS) were 92% and 72.6%, 92.2% and 85.6%, 84.8% and 73%, 82% and 67.3%, respectively. Notably, only histologic grade emerged as a statistically significant prognostic factor, influencing both OS (p=0.019), DMFS (p=0.014), and DFS (p=0.044).
 Conclusion: The histologic grade of the tumor is the foremost determinant impacting the outcomes of MEC cases. Adjuvant radiotherapy is recommended for high-grade tumors, while its application for low-grade and intermediate-grade tumors should be individualized based on the anticipated risk of recurrence. This underscores the significance of tailoring treatment approaches according to histologic characteristics.

Study on the Dynamic Changes of Myocardial Injury Markers in Radiotherapy for Esophageal Carcinoma and Its Correlation with Cardiac Dosimetry

It was hypothesized that radiotherapy for esophageal cancer could cause radiation-induced heart damage. To investigate the dynamic changes of myocardial enzyme, high-sensitive troponin T (hs-TnT), N-terminal pro-brain natriuretic peptide precursors (PRO-BNP) and left ventricular ejection fraction (LVEF) during radiotherapy and six months after radiotherapy for middle and lower thoracic squamous cell carcinoma, and to analyze the correlation between these indicators and dose-volume histogram (DVH) parameters of the heart. A total of 35 patients with thoracic esophageal squamous cell carcinoma who underwent radical concurrent chemoradiotherapy were enrolled in the study. Radiation therapy was performed for up to 6 weeks. All patients received Intensity modulated radiation therapy (IMRT). Total radiation dose was from 50.4Gy to 60 Gy in each patient with a dose of 1.8-2.0 Gy per fraction. Blood samples to determine creatine kinase (CK), creatine kinase isoenzyme MB (CK-MB), lactic dehydrogenase (LDH), alpha-hydroxybutyric dehydrogenase (α-HBDH), hs-TnT, PRO-BNP and LVEF were measured before radiotherapy, during (10th -20th fraction), at the end of radiotherapy, 1, 3, 6 months after radiotherapy. The dynamic changes of the above indexes were analyzed. The correlation between the above indexes and the mean heart dose (Dmean), V5-V60 (dose-volume histograms data were recorded in discrete 5Gy dose levels) of the heart in the course of radiotherapy was also analyzed. The Serum hs-TNT and LVEF show an upward trend during radiotherapy, at the end of radiotherapy and 6 months after radiotherapy for esophageal cancer. The hs-TnT of patients before, during, at the end of radiotherapy and 1, 3, and 6 months after radiotherapy were 7.2pg/ml, 9.1pg/ml, 9.1pg/ml, 9.0pg/ml, 9.4pg/ml, and 8.1pg/ml, respectively (p<0.05). The LVEF were 63.7%, 62.4%, 62.0%, 62.5%, 62.2%, 61.9% respectively (p<0.05). The pro-BNP showed an upward trend during radiotherapy and gradually returned to normal after radiotherapy. The CK and CK-MB showed a downward trend during radiotherapy and 1 month after radiotherapy, and gradually returned to normal 3 months after radiotherapy. Compared with the low dose group (the average dose of heart < 2000cGy), the high dose group (≥2000cGy) had a greater increase in hs-TNT, pro-BNP and LVEF, and a slower recovery time. There was no correlation between the changes of myocardial enzyme, hs-TnT, PRO-BNP, LVEF and the heart mean dose, V5-V60 during radiotherapy (p>0.05). Cardiac injury induced by concurrent chemoradiotherapy for middle and lower thoracic esophageal cancer can lead to the increase of serum hs-TNT and pro-BNP and the increase of LVEF in the early stage of treatment, and this phenomenon is more obvious in the high-dose group. The hs-TnT and PRO-BNP are sensitive parameters to reflect the heart damage in esophageal cancer radiotherapy, which may provide reference for the heart protection during radiotherapy.

Long-Term Clinical Outcome of Carbon Ion Radio Therapy for Hepatocellular Carcinoma in the Caudate Lobe

Surgical resection is the first-line treatment for hepatocellular carcinoma in the caudate lobe (caudate HCC), but it is often difficult due to the tumor's location. In addition, radiofrequency ablation and transcatheter arterial chemoembolization are also difficult for the same reason. This study aimed to evaluate the safety and efficacy of carbon-ion radiation therapy (C-ion RT) for caudate HCC. We performed a retrospective cohort study of patients with hepatocellular carcinoma treated by C-ion RT between April 2000 and March 2020 in our institution. The eligibility criteria for this study were: (1) located mainly in the caudate lobe (2) the treatment protocols of 45.0-48.0 Gy/2 fractions or 52.8-60.0 Gy/4 fractions, which proved the safety and efficacy in the past clinical trials; (3) N0M0 status; (4) an Eastern Cooperative Oncology Group performance status (PS) of 0 to 2; (5) controllable ascites. The prescribed dose (Gy) used in this study is relative biological effectiveness (RBE) weighted dose. Overall survival (OS), progression-free survival (PFS), and local control rate (LC) were calculated by the Kaplan-Meier method. Adverse events were evaluated by NCI-CTCAE ver. 5.0. SPSS software version 27.0 (IBM Inc.) was used for all analyses. We defined p-value < 0.05 as statistically significant. A total of 25 patients met the criteria and were evaluated. The median patient age was 73 years (range 58-89), and 21 of 25 patients were male. The number of patients with PS 0 was 22, PS 1 was 1, and PS 2 was 2. The number of HBV-related HCC cases was in 8, HCV-related HCC cases was in 11, and non-B and non-C cases was in 6. The median maximum tumor diameter was 3.0 cm (1.1-4.8 cm). In 6 patients, identification of vascular invasion to the main trunk of the portal vein and/or major hepatic vein was confirmed. The Child-Pugh (CP) grade was A in 21 patients and B in 4. The modified albumin-bilirubin (mALBI) grade 1 is in 17 patients, 2a in 4, 2b in 4. Prescribed doses were 45 Gy / 2 fr in 3 cases, 48 Gy / 2 fr in 12 cases, 52.8 Gy / 4 fr in 7 cases, and 60 Gy / 4 fr in 3 cases. With a median follow-up period of 43.6 months (range 0.3-85.0), 3-year OS, PFS, and LC were 74% (95% confidence interval [CI], 54.8-93.8%), 32% (95% CI, 11.8-51.4%), and 93% (95% CI, 79.4-106%), respectively. All patients had no Grade 2 or higher adverse events during the observation period. The safety and efficacy of C-ion RT for caudate HCC were demonstrated. These results suggested that C-ion RT may be a promising treatment option for patients with caudate HCC.

Unique T-cell Sub-Population Shifts after SBPT and Nivolumab in Platinum Refractory HNC: Biomarker Correlates from ROR1771

ROR1771 was a clinical trial investigating the use of stereotactic body proton radiotherapy (SBPT) and nivolumab in recurrent platinum refractory head and neck squamous cell carcinoma (HNSCC). The planned analysis of T-cell subpopulation and biomarker response is herein presented. Patients with metastatic histologically confirmed HNSCC from any primary site received 2 cycles of nivolumab followed by SBPT to 1-2 selected target lesion(s) (hilar/lung: 8 of 12 patients), followed by maintenance nivolumab. Peripheral blood mononuclear cells were isolated pre-/post-treatment. Flow cytometry identified T-cell subpopulations. Single Cell 5' Gene Expression (GEX) and V(D)J T Cell Receptor libraries were prepared using Single Cell Immune Profiling. Seurat (v4.1.1) was used to identify cell type clusters, and differential expression post-filtration was evaluated using the Wilcoxon Rank Sum test. A total of 12 patients were eligible for analysis, with one alive at time of analysis, 52 months from start of treatment. Median overall survival here was 12.5 months vs. 7.5-months on CheckMate 141. SBPT ranged from 35-50 Gy. Sequential changes in T-cell populations from baseline were noted with initiation of nivolumab, driving decrease in tumor-reactive (TTR; CD11ahighPD1+CD8+), central memory (TCM; CCR7+CD45RA-), and effector T-cells (TEF; CCR7-CD45RA-). TTR and TCM increased following SBPT, with greatest increase (3.5x TTR and 5.2x TCM) in the surviving patient. An average of 68 genes with significant differential expression between timepoints (p<0.0001) demonstrated RNA gene expression changes across all cell subtypes, including ribosomal (RPL and RPS) genes, ACTB, FTL, MALAT1, and others. This averaged 113 genes across all timepoints in the surviving patient, with peak following nivolumab induction. On T-cell receptor (TCR) analysis of this patient, the predominant clonotype diversity changed substantially following nivolumab. Following SBPT, clonotype diversity again changed to include a milieu seen neither at baseline nor with nivolumab alone. These TCRs persisted for approximately 2 weeks following SBPT before returning to resemble the nivolumab-induced TCR diversity alone, coinciding with disease recurrence. ROR1771 demonstrated overall survival favorably comparable to CheckMate 141. Biomarker analysis of peripheral blood samples demonstrated significant shifts in T-cell subpopulations and underlying gene expression to nivolumab and then to SBPT administration. SBPT to a target lesion changed TCR clonotypes within the peripheral blood beyond those seen with nivolumab administration, with fading of these TCR clonotypes coinciding with recurrence. SBPT in combination with nivolumab may drive systemic immunologic change above that induced by nivolumab alone and warrants further investigation.

Long-term follow-up of osteoradionecrosis of the mandible

Aim Investigating the prevalence of mandibular ORN in a single Swedish Oncology Center. Methods A total of 450 patients, treated with radiotherapy for squamous cell carcinoma in the oropharynx between 2004 and 2014 were included. Three different techniques of radiotherapy were studied. ORN diagnosis was set when clinical signs according to Marx were observed, or if radiological signs were staged according to Schwartz and Kagan. Results Using the staging system, 90 patients (20%) were diagnosed with ORN. The mean age of the ORN patients was 56.6 years, the older the patient the lower the risk of developing ORN (p = .01). The risk of developing ORN for patients receiving Intensity Modulated Radiotherapy was lower compared to patients treated with the other techniques in the multivariable analysis. Brachytherapy significantly increases the risk of ORN. The risk of ORN increased by 8% each year after radiation (p = .04). The mean time to the ORN diagnosis was 3.9 years. In the multivariate analysis, the risk of ORN increased by 13% each year after radiation (p = .0013). Conclusion The mean radiation dose was of greater importance for the risk of ORN than the maximum dose. Elderly people with oropharyngeal cancer were less prone to develop ORN.

Weekly vs. Bolus Cisplatin Concurrent with Definitive Radiotherapy for Squamous Carcinoma of the Head and Neck: A Systematic Review and Network Meta-Analysis

The optimal schedule for cisplatin delivered concurrently with definitive radiation for squamous carcinoma of the head and neck remains controversial. Randomized data in the postoperative setting is mixed, and definitive studies are ongoing. Meanwhile, multiple trials have already compared cetuximab to cisplatin in the definitive setting. Across these trials, the cetuximab dosing was identical, but cisplatin dosing was variable and can be categorized as weekly (40 mg/m2 q1 week) or bolus (100 mg/m2 q3 weeks). We indirectly compared these two cisplatin schedules by performing a network meta-analysis of cetuximab trials. We performed a PRISMA-concordant systematic review to identify randomized controlled trials comparing cisplatin to cetuximab for patients with non-metastatic squamous carcinoma of the head and neck treated with definitive radiation therapy. Trials of primary surgery, incorporating induction therapy, or mixing other therapeutics were excluded. The analysis was pre-registered with the Open Science Foundation. Individual patient survival data was extracted from the published overall survival curves using a digitizer, and outcomes were validated against published point-estimates and hazard ratios. A random effects Cox regression was used to perform the individual-patient analysis using a one-step approach under a frequentist framework. Random effects were applied to model heterogeneity in the baseline hazard function and treatment effect. Models were adjusted by HPV and smoking status, which were trial-level covariates. Alternative endpoints (DFS, LRF, DM, etc.) were analyzed qualitatively. IRB approval was not required. Five randomized trials were identified, including 1,678 patients. Bolus cisplatin was delivered to 572 patients in 2 trials, and weekly to 271 in 3 trials. The risk of bias was low. Relative to cetuximab, both bolus and weekly cisplatin reduced the risk of death (adjusted HR 0.63, 95% CI 0.46-0.87, p = 0.004 & HR 0.56, 95% CI 0.37-0.86, p = 0.008 respectively). No interaction was identified between regimen and HPV or smoking status. Between-study heterogeneity (δ2) was 0.148 and treatment effect heterogeneity (τ2) was small (<0.0002). There was no statistical difference in OS between bolus vs. weekly regimens (weekly vs. bolus HR 0.90, 95% CI 0.53-1.52, p = 0.345). This Cox model therefore suggested that on average, the absolute difference in 5-year OS is <1.5% between the two regimens, which was not statistically significant. Secondary endpoints and toxicity were not obviously different by regimen, qualitatively. Using cetuximab as a common reference, there was no significant difference in survival between weekly and bolus cisplatin schedules.

Efficacy and Safety of Image-Guided Hypofractionated Radiotherapy for Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis

To evaluate the efficacy and safety of image-guided 10-fraction hypofractionated radiotherapy (RT) in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT). Between 2016 and March 2022, 69 HCC with PVTT patients received RT (40-50Gy/10fx) in our institutions. The median prescribed dose of 50 Gy (range, 40-50 Gy, BED10; 56-75 Gy10) was delivered in 10 fractions in all patients. Follow-up imaging was performed at three-month intervals after the completion of RT. The extent of PVTT was described according to the Liver Cancer Study Group of Japan classification: Vp0 = no PVTT, Vp1 = segmental portal vein branch, Vp2 = right/left anterior/posterior portal vein, Vp3 = right/left portal vein and Vp4 = main portal vein. Response evaluation was performed using response evaluation criteria in solid tumors, version 1.1. Freedom from local progression (FFLP), progression-free survival (PFS), and overall survival (OS) were calculated from the start date of RT. In this cohort, 4.3% of patients had Vp1 PVTT, 20.3% had Vp2, 37.7% had Vp3, and 37.7% had Vp4. The median PTV volume was 105.3 cc (interquartile range [IQR], 74.1-179.4 cc). Fifty-two (75.4%) patients received 50 Gy in 10 fractions. With a median follow-up of 10.2 months (IQR, 6-21 months), the median OS was 18.5 months, and 1-year FFLP, PFS, and OS rates were 84.8%, 26.9%, and 62.2% respectively. At 3 months after RT, 13.0% had a complete response, 36.2% had a partial response, 46.4% had a stable disease and 4.4% had a progressive disease. In the multivariate analysis, AFP ≥ 600 IU/ml (HR 2.06, p = 0.03), Child-Pugh Class B or C (HR 2.30, p = 0.02), and modified Union for International Cancer Control (mUICC) stage IVA or IVB (4.05, p = 0.02) were significantly related to OS. During the follow-up period, there were 2 (2.8%) cases of grade ≥3 toxicity: grade 3 AST/ALT elevation (n = 1), and acute cholangitis (n = 1). Hypofractionated RT demonstrated promising local PVTT control with acceptable toxicity. These data suggest that 10-fraction image-guided hypofractionated RT (BED10 = 56-75 Gy10) is a feasible treatment option for PVTT in HCC patients.

Quality of Life Before and after Radiotherapy for Early-Stage Keratinocyte Carcinoma: A Longitudinal Analysis

Cutaneous squamous and basal cell carcinoma (keratinocyte carcinoma, KC) are common malignancies treated with radiotherapy (RT) to preserve form and function. Treatment of KC can compromise quality of life (QOL), but little is known about patient-reported QOL before and after RT for early KC. The purpose of this study was to assess prospectively collected patient-reported QOL before and after RT for early KC and compare this to previously reported studies of other treatments. It was hypothesized that QOL deteriorates soon after RT, with subsequent improvement of a magnitude similar to previously published reports of other KC treatments. Patients undergoing RT for early-stage (T0-2, <4 cm) KC who completed a QOL assessment before and at least once after RT were the subjects of study. Characteristics of patients, tumors and treatment were recorded. Patient-reported QOL was measured by 2 validated indices: Skindex-16 (S16, including subscales of symptoms, emotions, functioning; lower score is better QOL) and Skin Cancer Index (SCI, including emotional, social and appearance subscales; higher score is better QOL). Paired t-tests compared scores before and at 4 time points after treatment (6 weeks, 3 months, 1 and 2+ years), with a ≥10-point difference considered clinically significant, and a p<0.0125 considered statistically significant due to Bonferroni correction. A total of 85 patients (median age 79 years) with early KC, most of which were basal cell carcinomas (87%) on the face (80%) and an average of 1.3 cm in diameter were treated with a median of 48 Gy in 12 fractions. Composite S16 scores and total SCI scores showed significant, clinically meaningful improvements 3 months (15.2→5.2) and 6 weeks (72.0→85.7) after RT. Non-significant declines in QOL happened 6 weeks after treatment on the S16 symptom subscale (11.3→16.6). Concurrently, S16 and SCI emotional subscales (25.9→14.4 and 67.2→79.3) significantly improved, and this trend persisted for 2+ years. Improvements in S16 functioning (8.7→2.8) and SCI social (80.2→89.6) and appearance (68.6→90.5) QOL occurred. S16 demonstrated that 1-2 years after treatment, composite QOL improved by 45%, 47%, 39% and 10% in patients treated with RT, Mohs surgery, excision and electrodessication and curettage, respectively. SCI demonstrated that 3-4 months after treatment, total QOL improved by 24% and 4-13% after RT and Mohs surgery, respectively. QOL related to symptoms deteriorates at 6 weeks after RT, with clinically and statistically significant improvement seen by 3 months after RT. QOL related to emotions, functioning, social and appearance domains all improve after RT. The changes in QOL are similar if not greater than those observed after other treatments of early KC, and may help guide patient expectations following RT.

Radiotherapy (RT) for Cutaneous Adnexal Carcinoma (CAC): 49 Patients Treated at a Single Institution Over 2 Decades

Cutaneous adnexal carcinomas (CACs) are a heterogenous group of rare skin cancers. Management strategies are extrapolated from the treatment of more common skin cancers, and case series describing patients treated with radiotherapy (RT) for CAC are limited to <15 patients. We reviewed our institutional experience to better understand the characteristics and outcomes of patients with CAC treated with RT. Patients diagnosed with CAC and treated RT from 2000-2020 were identified using the following keywords: adnexal, microcystic, apocrine, eccrine, sebaceous, sweat gland, syringoma, mucinous, tubular, porocarcinoma, hidradenocarcinoma, and cylindrocarcinoma. Patient, cancer, and treatment characteristics were assessed by retrospective record review. Time to overall survival (OS), locoregional recurrence (LRR), distant metastasis (DM), and progression free survival (PFS) were evaluated using Kaplan-Meier methods. Forty-nine patients with a median age of 65 years (IQR 53-82) were identified. Most were white (90%) men (59%) harboring tumors on the head and neck (80%). The most common subtypes of CAC were adnexal adenocarcinoma (39%), sebaceous carcinoma (35%) and microcystic adnexal carcinoma (10%). Patients were treated for de novo cancer (n = 35) or after recurrence (n = 14). Among de novo cases, 9 (26%) were treated with definitive RT, 22 (63%) were treated with surgery and adjuvant RT, and 4 (11%) with palliative RT. Per UICC system, de novo stage at time of RT was I in 2 (6%), II in 9 (26%), III in 12 (34%), IVA in 10 (29%), and IVB in 2 (6%). Median OS was 44 months and median follow-up of surviving patients was 41 months (IQR 17-75). De novo patients treated with definitive RT received a median dose of 70 Gy (IQR 60-73 Gy) and experienced 2-year rates of PFS, LRR, and DM of 30%, 55%, and 40%, respectively. All LRR events occurred within the irradiated volume. De novo patients treated with surgery and adjuvant RT received a median dose of 60 Gy (IQR 60-64 Gy) and experienced 2-year rates of PFS, LRR, and DM of 77%, 13%, and 10%, respectively. All LRR events occurred outside the irradiated volume. Among patients treated at recurrence, most (93%) underwent surgery and adjuvant RT. Per UICC system, their stage at time of RT was II in 2 (15.4%), III in 4 (30.8%), and IVA in 7 (53.8%). Recurrent patients treated with surgery and adjuvant RT received a median dose of 60 Gy (IQR 60-66 Gy) and experienced 2-year rates of PFS, LRR, and DM of 30%, 58%, and 29%, respectively. Three of 4 evaluable patients treated with palliative RT exhibited stable disease or tumor response. In the largest single institution analysis to date, RT was primarily used for CAC patients as an adjuvant treatment. LRR was less frequent and less likely to occur within irradiated volume in patients selected for surgery and adjuvant RT than those selected for definitive RT or at time of recurrence.

All-in-One Online Radiotherapy for Nasopharyngeal Carcinoma: Preliminary Results of Treatment Time, Contouring Accuracy, Treatment Plan Quality and Patient Compliance

To explore the feasibility of Fan-beam CT (FBCT)-based all in one (AIO) online workflow for nasopharyngeal carcinoma (NPC) in radical radiotherapy setting, and to preliminarily describe the timing of different steps in the process, contouring accuracy of regions of interest (ROIs), target coverage, organs at risk (OARs) dose and patient compliance. From March 16, 2022 to January 04, 2023, 25 NPC patients (22/25 diagnosed as phase III/IV disease according to 8th edition of the AJCC/UICC staging system) consecutively treated with AIO radiotherapy were prospectively enrolled. All patients received mask fixation and MRI simulation scan in advance. Primary gross tumor volume (GTVp) of nasopharynx was automatically delineated by AI and edited manually on MRI images. AIO online workflow started with an integrated KV-level CT in a CT-integrated linear accelerator. After that GTVp was registrated to CT images and other ROIs was contoured automatically and then modified manually as needed. Subsequently automatic treatment plan was calculated and optimized until the dose of target and OARs was evaluated satisfactory by physicians and physicists. Finally, treatment was delivered using volumetric modulated arc treatment (VMAT), with prescribed dose of 6996 cGy/ 33 fractions to the GTVp. Twenty-four patients (24/25, 96%) completed the AIO radiotherapy workflow successfully, with average treatment time of 28.3 min (range: 19.9-42.4 min). the AI-assisted ROIs automatically contouring took 1.55 min in average (range: 1.32-1.77 min), with an average DICE of 97.7% compared with modified contouring, and the average DICE was 95.7% for clinical tumor volume 1 (CTV1), 88.6% for CTV2, 73.6% for GTVn (cervical lymph node), 99.3% for 30 OARs. The automatic treatment plan averagely needed 3.5 min, and the pass rate of radiotherapy planning was 91.7% (22/24). The target coverage for PTVs for GTVp, CTV1, and CTV2 was 99.3%, 99.8%, 98.0% respectively. As for the dose of OARs, the average Dmax of brainstem was 5,583cGy; the Dmax of spinal cord was 3,467cGy; the Dmean of parotid was 3,285 cGy. The average monitor units of all patients was 643 MU and the delivery took 2.93 min. Patient compliance with respect to AIO workflow and total treatment time was excellent. The AIO online radiotherapy was promising for NPC patients, with clinically acceptable AI assisted ROIs contouring and treatment planning, as well as favorable patient compliance to the AIO online workflow.

First Implementation of Full-Workflow Automation for Online Adaptive Radiotherapy of Nasopharyngeal Carcinoma

The aim of this work is to established the technical characteristics and implementation procedures of an artificial intelligence (AI)-powered radiotherapy workflow that enables full-process automation for online adaptive radiotherapy (ART); and evaluate its feasibility and performance implemented for ART of nasopharyngeal carcinoma (NPC). This single center, prospective study has been approved by the ethical committee of the institution. The online ART workflow was developed based on a CT-integrated linear accelerator. During the course of radiotherapy, the patient underwent daily pre-treatment fan-beam CT (FBCT) scan. Then the FBCT was automatically registered to the original planning CT and used to assess the need for the patient to implement ART according to radiation oncologist's discretionary. The online ART workflow incorporates critical radiotherapy procedures from re-simulation, auto-segmentation by integrating image fusion and deep learning method, auto-replanning, beam delivery, and in vivo quality assurance (QA) into one scheme, while the patient is on the treatment couch during the whole process. From 2th April 2022 to 5th January 2023, 20 patients with newly-diagnosed, non-metastatic NPC were enrolled in this study. Only one-time online ART was performed for each patient, because that the appropriate timing for triggering online ART was explored in parallel with this study. According to radiation oncologists' discretionary, the median fraction for performing online ART was at 21 fractions (interquartile range, 19-24 fractions). All patients were well tolerated and successfully completed the treatment. For tumor targets contouring, minor revisions were required for automated contours of the primary gross tumor volume (GTVp) and clinical target volumes (CTVs, including CTV1 and CTV2), with the mean DSC between before and after revision of 0.91±0.042, 0.94 ± 0.042 and 0.91 ± 0.061, respectively; and much more revisions for the automated contours of cervical lymph nodes GTV (GTVn), with the mean DSC of 0.74 ± 0.28. The automated contours of normal tissues were clinically acceptable with little modifications. Median time consuming for auto-segmentation and revision was 9.5 minutes (min). For treatment planning, 18 automated plans (90%) were passed at their first auto-optimization and two plans (10%) were passed after further optimization of the dose coverage of CTVs by physicist; and the median time consuming for auto-planning was 6.2 min. Time consuming for other procedures were as follows: re-simulation, 2.3 min; plan evaluation, 3.3 min; beam delivery, 4.6 min; and the duration of the entire process was 25.9 min, range from 19.4 min to 32.5 min. We successfully established an AI-powered online ART workflow for adaptive radiotherapy of NPC, and confirmed that current auto-segmentation and auto-replanning methods are powered enough to support the clinical application of its online ART.

Challenging the Role of Subtotal Resection Following Proton Radiotherapy for Adenoid Cystic Carcinoma of the Head and Neck

To report long-term outcomes of patients with adenoid cystic carcinoma (ACC) of the head and neck treated with proton radiotherapy. On this IRB-approved, single institutional prospective outcomes registry, 56 patients were included with de novo, nonmetastatic adenoid carcinoma of the head and neck treated with primary (n = 9) or adjuvant proton therapy from June 2007 to December 2021. The cohort had 30 women and 26 men with a median age of 57 years (range, 10-81 years). Twenty-nine percent (n = 16) had intracranial extension, 23% (n = 13) had orbital extension, and 55% (n = 31) had clinical cranial nerve involvement at the time of radiotherapy. Thirty patients underwent gross total resection (GTR), 26 had gross disease at the time of treatment undergoing a subtotal resection (STR) (n = 17) or biopsy alone (n = 9). The median dose to the primary site was 72.6 GyRBE (range, 64-74.4 GyRBE) delivered in either once (n = 19) or twice (n = 37) daily treatments. Thirty patients received either elective nodal irradiation (ENI) in a node negative neck or concurrent chemotherapy. With a median follow-up of 6.2 years (range, 0.9 - 14.7 years), the 5-year local-regional control (LRC), disease free survival (DFS), cause-specific survival (CCS) and overall survival (OS) were 88%, 85%, 89%, and 89%, respectively. Cranial extension (p = 0.003) and gross residual tumor (p = 0.0388) were factors associated with decreased LRC. While LRC for those with a GTR was 96%, those with STR or biopsy alone were 81% and 76%, respectively. T-stage (p = 0.0154), cranial extension (p = 0.0056), extent of resection (p = 0.0355), and gross residual tumor (p = 0.0094) were associated with decreased DFS. T-stage (p = 0.0099), extent of surgery (p = 0.029) and gross residual tumor (p.0071) were associated with decreased CCS. The 5-year cumulative incidence of clinically significant late grade ³3 toxicity was 15% and the crude incidence at most recent follow-up was 23% (n = 13). There was no LRC benefit with ENI (p = 0.94). Proton therapy provides excellent disease control for head and neck ACC with acceptable toxicity. Gross residual disease at the time of treatment and intracranial involvement were significant prognostic features for worse outcomes. STR did not confer benefit over biopsy only at 5-years and may question the role of extensive and morbid operations if GTR is not technically feasible.

Association of radiotherapy with thoracic vertebral fractures in esophageal squamous cell carcinoma: A retrospective cohort study.

To investigate the association between radiotherapy (RT) and thoracic vertebral fractures in esophageal squamous cell carcinoma (ESCC) and explore the risk factors of thoracic vertebral fracture in ESCC who underwent RT. This retrospective cohort study including 602 consecutive ESCC patients examined the association between RT and thoracic vertebral fractures using multivariable Cox proportional hazard models and relevant risk factors of thoracic vertebral fractures based on clinical and RT parameters in patients with ESCC. Followed for a median follow-up of 24 months, 54 patients had thoracic vertebral fractures. The multivariable analysis revealed RT as an independent risk factor after adjusting for clinical risk factors. Univariable analyses associated a 5-Gy increase in vertebral dose to single vertebrae and a 1-time increase in RT fraction with higher risk of vertebral fracture. Adding RT factors (vertebral dose and fraction) and mean vertebral hounsfield unit to the Cox models containing conventional clinical risk factors significantly improved the χ2 value for predicting vertebral fractures (all P < .001). This study revealed RT, as well as increased vertebral dose and RT fractions, as a significant, consistent, and strong vertebral fracture predictor in ESCC. Combined vertebral dose, RT fractions, and vertebral hounsfield unit provided optimal risk stratification for ESCC patients.

Risk of Radiation-Associated Secondary Malignancies among Patients with Breast Cancer Harboring TP53 Germline Variants

Radiation-associated malignancies are rare and poorly understood. TP53 encodes a multifunctional protein that maintains genome integrity and is the most common somatically mutated gene in cancer. Germline pathogenic variants of TP53 predispose carriers to several cancers comprising the Li-Fraumeni syndrome. It is hypothesized that carriers are also at increased risk of radiotherapy (RT)-associated secondary malignancies; however, reports are mixed. We evaluated the risk of secondary malignancies after breast RT among patients with Li-Fraumeni syndrome. This multi-institutional cohort study included carriers of TP53 germline variants who underwent surgical treatment for breast cancer between 1980 and 2020. Patients were stratified based on germline TP53 classification (pathogenic variants [PV] vs variants of uncertain significance [VUS]). The primary outcome of interest was the cumulative incidence risk of developing an in-field secondary cancer after radiotherapy for primary breast carcinoma. Ninety-one patients (57 PV and 34 VUS) were evaluated with a median age of 36 years (interquartile range [IQR] 31, 42) and a median follow up of 7.9 years (IQR 4.7, 14.4). Among those with PV who received RT (n = 22), 4 secondary non-breast cancers developed in the radiation field (15-year cumulative incidence 19% [95% CI: 4-43%]), whereas, among those with PV who did not receive RT (n = 35), 0 secondary non-breast cancers were observed in the treated breast (15-year cumulative incidence 0%; p = 0.043). We observed 3 radiation-associated sarcomas among patients with PV who received RT (15-year risk 12% [95% CI 2-33%]) compared with 0 among those who did not receive RT (p = 0.08). No RT-associated sarcomas were observed among 18 patients with TP53 VUS who received RT. RT was not associated with overall survival, despite higher T and N breast cancer stage among those receiving RT (p = 0.33). As expected, patients with PV were more likely than those with VUS to develop any secondary cancer following breast cancer treatment (15-year risk: 54% [95% CI: 33-72%] vs. 14% [95% CI: 3-36%]). Carriers of pathogenic variants of TP53 are at elevated risk of developing secondary malignancies after breast cancer treatment. This population is at particular risk of developing in-field secondary cancers following RT. This iatrogenic risk must be weighed against the anticipated therapeutic benefit of tumor control. Shared decision making is crucial in the radiotherapeutic management of breast cancer patients harboring the Li-Fraumeni syndrome.

Prediction of Anatomical Presentation during Radiotherapy of Nasopharyngeal Carcinoma Using GAN-LSTM for Plan Adaption Decision

During treatment, patients frequently undergo anatomical changes that might result in dose degradation. Adaptive radiation therapy (ART) is now available to overcome this problem. However, this method is time-consuming, and the lack of criteria to trigger replanning prevents its widespread use. To overcome these obstacles, anatomical presentation models are necessary. In this study, we developed a novel deep-learning method to make a series of predictions for the remaining treatment course. Total 230 nasopharyngeal carcinoma patients who received radiotherapy in 33 fractions were enrolled. The data included cone-beam computed tomography (CBCT) and planning CT images. CBCT image quality was improved to CT level using an in-house software. A generative adversarial network-long short-term memory network model was proposed, with the generation abilities of the former network and forecasting abilities of the latter. To predict the anatomical presentation for 3-6 weeks, we trained four models. The planning CT and CBCT acquired earlier were used as the input. Physicians segmented the gross target volume (GTVnx) and parotid glands on prediction and real CBCT (ground truth). Contours, dosimetry parameters, and plan adaptation decision were used to evaluate the models. The table shows the overall performance of the test set (18 cases). The anatomical changes were predicted over the treatment course with a dice similarity coefficient (DSC) of 0.96, 0.90 and 0.92 and mean distance to agreement (MDA, in mm) of 0.37, 0.70, and 0.60 for GTVnx, left parotid, and right parotid, respectively. Bland-Altman analysis revealed that dosimetry parameters did not show significant difference between prediction and ground truth. The prescription coverage (%) of GTVnx, V30 of the left parotid, and V30 of the right parotid had mean absolute biases of 0.09, 1.09, and 0.27, respectively. At week 6, there were two cases that required plan adaptation, and the model effectively triggered replanning one week in advance. We developed a framework that predicts the anatomical changes occurring in future fractions. Establishing such a framework provides a proactive approach to ART and saves clinical time by anticipating and preparing for treatment strategies in advance.

Automated Contouring of Cervical Lymph Nodes and Clinical Target Volumes for Nasopharyngeal Carcinoma Based on Deep Learning and Experience Constraints

Application of artificial intelligence (AI) for automated contouring of tumor volumes and organs at risk (OARs) for radiotherapy of nasopharyngeal carcinoma (NPC) leads to improved contouring accuracy and efficiency. However, few studies have involved the automated contouring of gross tumor volume of cervical lymph nodes (GTVn) and clinical target volumes (CTVs). In this work, we proposed an AI automated contouring tool for GTVn and CTVs for radiotherapy of NPC on the plain scans of planning compute tomography (CT). In this retrospective study, plain scan datasets of planning CT covering the nasopharynx and neck from 139 patients with NPC between March 2022 and December 2022 were collected and divided into training, validation, and testing cohorts of 95, 24, and 20 patients, respectively. Ground truth contours of primary gross tumor volume (GTVp), GTVn (divided into GTVn_L in left neck and GTVn_R in right neck), CTVs (including high risk CTV1 contains GTVp and low risk CTV2 contains GTVp and cervical nodal levels) and OARs were delineated and were defined by consensus of two experts. We first proposed a three-dimensional (3D) U-net using GTVp and OARs as experience constrains to guide the automated delineation of GTVn and CTVs. The average Dice similarity coefficient (DSC) and average surface distance (ASD) were used to quantify the performance of the AI tool. Next, five prospective patients were enrolled for clinical evaluation of our AI tool. DSC between automated contours and radiation oncologist-revised contours and time consuming of the revision were record. Clinical characteristics of 139 retrospective and 5 prospective patients are list in Table 1. In the independent testing set of 20 patients, our AI tool showed high performance in GTVn and CTVs contouring when compared with the ground truth contours. The mean DSC were 0.73 ± 0.07, 0.74 ± 0.05, 0.93 ± 0.03, and 0.88 ± 0.03, and the mean ASD were 1.01 ± 0.43 mm, 1.14 ± 0.61 mm, 0.51 ± 0.13 mm, 1.17 ± 0.43 mm for GTVn_L, GTVn_R, CTV1 and CTV2, respectively. In the five prospective patients, mean DSC were 0.74 ± 0.07, 0.74 ± 0.10, 0.95 ± 0.01 and 0.89 ± 0.04, respectively. The median time consuming for GTVn and CTVs revision was 2minutes and 10 seconds (range, 1 minutes to 3 minutes). The proposed AI tool integrating clinical experience as constrains showed high accuracy for contouring GTVn and CTVs of NPC. With the assistance of AI contours, contouring efficiency could be probably increased, which is promising in online adaptive radiotherapy of NPC.

Intratumoral Dose Escalation Using Lattice Radiotherapy for Hepatocellular Carcinoma with Unfavorable Size and Location

Stereotactic body radiation therapy (SBRT) is a standard of care for unresectable hepatocellular carcinoma (HCC). However, its safe delivery is limited by tumor size and adjacent organs-at-risk (OARs). RTOG 1112 showed a survival benefit with local control in advanced HCC, but median dose was limited to 35 Gy in 5 fractions due to OARs. Here, we demonstrate the dosimetric feasibility of lattice radiation therapy (LRT) for dose escalation in advanced HCC. Five-fraction volumetric arc-based (VMAT) LRT plans were generated using a customized Python v3.6 script. For each combination of peak/valley doses and sphere size and spacing, a bounding box was generated around the gross tumor volume (GTV) and divided into equal segments in the x, y, and z planes. Individual spheres were constructed for a given parameter set and those fully encompassed within the target contracted by 2 cm were used to create peak dose targets with values of 30, 40, or 50 Gy. Valley dose target volumes over a range of 2 to 45 Gy were generated by subtracting an 8 mm expansion of the peak dose spheres from the overall target volume. Multi-criteria optimization (MCO) was applied to generate a final plan. The planning target volume (PTV) was a 5-mm uniform expansion from the GTV. All plans were generated at maximum inspiration on 4D-CT. OAR parameters were compared against a standard 5-fraction SBRT plan using Wilcoxon signed-rank testing. GTV and PTV measured 593 (23%) and 804 (32%) cm3, respectively, of a total liver volume of 2525 cm3. The minimum distance of GTV from stomach and duodenum was 6 mm and 2 mm, respectively. Plans were evaluated as per RTOG 1112 with stepwise reduction from a maximum PTV dose of 50 Gy based upon ability to meet mean liver dose (MLD, defined as liver-GTV) constraints; the 30 Gy threshold was the highest achievable. Of 7 eligible LRT plans, 5 with ablative 50 Gy peak doses were analyzed. Associated valley doses were 15 or 20 Gy. Median values of mean GTV and PTV doses for these plans were 36.2 (IQR, 34.6 - 37.8) and 32.9 (IQR, 31.3 - 33.4) Gy, respectively. A median of 12.4% (IQR, 7.4 - 28.4) of the GTV received a dose of 50 Gy. Median doses to 0.5 cc of stomach and duodenum were 16.7 Gy (range, 15.6 - 19.6) and 14.4 Gy (range, 12.3 - 23.9), respectively. The median value for MLD was 13.9 Gy (range, 13.6 to 14.8) and the median volume of normal liver spared 15 Gy was 1114 cm3 (range, 969 to 1154). These hepatic parameters were significantly decreased compared to a standard 30 Gy SBRT plan (18.1 Gy and 611.3 cc spared, p = 0.043 for both) which did not meet constraints. Dose escalation of advanced HCC using LRT is dosimetrically feasible. Though mean target doses remained limited by MLD, LRT allowed delivery of ablative dose to 12.4% of the GTV while meeting critical OAR constraints. Intratumoral dose-escalation may improve local control in advanced HCC patients.