Radiotherapy For Carcinoma Research Articles

Real-world Practice Patterns and Safety of Concurrent Radiotherapy and Cabozantinib in Metastatic Renal Cell Carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium

BackgroundThere is a paucity of data on the safety of cabozantinib use in combination with radiotherapy. ObjectiveTo report the practice patterns, safety, and efficacy of cabozantinib with radiotherapy in metastatic renal cell carcinoma (mRCC). Design, setting, and participantsAn international multicenter retrospective study was conducted. Patients with mRCC treated with cabozantinib at any line of therapy and who received radiotherapy between 30 d prior to the start date of cabozantinib and 30 d following discontinuation of cabozantinib, from 2014 to 2020, were included. Concurrent use was defined as the use of cabozantinib on radiotherapy treatment days during any course of radiotherapy. Outcome measurements and statistical analysisThe primary outcomes of interest were the rate of grade ≥3 adverse events (AEs) occurring within 90 d of receipt of radiotherapy. Secondary outcomes included hospitalization rate and patterns of cabozantinib and radiotherapy use. Baseline characteristics and AEs were presented descriptively. Results and limitationsA total of 127 consecutive patients were included. Most patients had clear cell histology (88%), had International Metastatic Renal Cell Carcinoma Database Consortium intermediate-risk disease (57%), and had received at least one prior line of therapy (93%). Of 127 patients, 67 (53%) received concurrent cabozantinib with radiotherapy, while the remaining held cabozantinib on radiotherapy days. Overall, grade 3–4 AEs occurred in 6.3% (n = 8/127) of patients. No grade 5 events were observed. In patients treated with conventional palliative radiotherapy (n = 88), the rate of grade 3–4 AEs in those who had concurrent versus those who had nonconcurrent cabozantinib was 6.3% (n = 3/48) versus 5.0% (n = 2/40). No patient was hospitalized due to radiotherapy-related toxicity. In patients treated with stereotactic ablative body radiotherapy (SABR; n = 50), the rate of grade 3–4 AEs in those who had concurrent versus those who had nonconcurrent cabozantinib was 3.6% (n = 1/28) versus 9.1% (n = 2/22). One patient in the nonconcurrent group was hospitalized due to muscle weakness suspected to be related to associated vasogenic edema 19 d after SABR for multiple brain metastases. ConclusionsIn this real-world study of patients with mRCC treated with cabozantinib, 53% of patients received radiotherapy concurrently, with few grade 3–4 AEs reported within 90 d of receiving radiotherapy. The use of radiotherapy and cabozantinib requires a risk-benefit assessment of patient and disease characteristics to optimize therapy regimens. Patient summaryOur study reports the real-world experience of using radiotherapy in patients receiving cabozantinib for metastatic kidney cancer. Over half of the patients continued taking cabozantinib while receiving radiotherapy, and few patients developed serious side effects. The combined use of radiotherapy and cabozantinib requires a careful risk-benefit assessment to achieve optimal treatment outcomes.

The development and validation of a decision aid to facilitate patient choice of surgery versus radiotherapy for high-risk basal cell carcinoma.

Basal cell carcinoma (BCC) is an increasingly common cancer. For high-risk BCCs, there are several treatment options, with similar efficacies. The current best practice in deciding upon a particular treatment is for a patient-centred approach. At present, there are few resources available for patients to assist their choice. This reduces patient autonomy and increases the burden on clinicians within clinic. Patient decision aids (PDAs) have been shown to increase patient autonomy and facilitate shared decision-making. Currently, there is no published PDA designed to facilitate the decision between surgical management or radiotherapy in high-risk BCCs. We developed a novel decision aid designed along the International Patient Decision Aid Standards to fill this clinical need, and evaluated its acceptance by both patients and clinicians. We describe the challenges faced at initial alpha and subsequent beta testing, and go on to validate our PDA with both the Decisional Conflict Scale and the nine-item Shared Decision Making Questionnaire (SDMQ9). We include an example of the PDA and encourage other units to modify the PDA for their own use.

Accuracy of response assessment FDG PET-CT post-(chemo)radiotherapy in HPV-negative oropharynx squamous cell carcinoma

Accuracy of response assessment FDG PET-CT post-(chemo)radiotherapy in HPV-negative oropharynx squamous cell carcinoma

Long-term outcomes and failure patterns of definitive radiotherapy for cervical esophageal carcinoma

Objective: To evaluate the long-term outcomes, failure patterns and prognostic factors of definitive radiotherapy in patients with cervical esophageal carcinoma (CEC). Methods: We retrospectively reviewed the clinical data of 148 CEC patients who treated with definitive radiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from January 2001 to December 2017. The median radiation dose was 66 Gy (59.4-70 Gy) and 33.1% of patients received concurrent chemotherapy. The Kaplan-Meier method was used to calculate survival rates. The log rank test was used for survival comparison and univariate prognostic analysis. The Cox model was used for multivariate prognostic analysis. Results: The median follow-up time was 102.6 months. The median survival time, 2- and 5-year overall survival (OS) were 22.7 months, 49.9% and 28.3%. The median, 2- and 5-year progression-free survival were 12.6 months, 35.8% and 25.8%. The 2- and 5-year locoregional recurrence-free survival were 59.1% and 50.8%. The 2- and 5-year distant metastases-free survival were 74.6% and 65.9%. Multivariate analysis showed that EQD(2)>66 Gy was the only independent prognostic indicator for OS (P=0.040). The median survival time and 5-year OS rate significantly improved in patients who received EQD(2)>66 Gy than those who received≤66 Gy (31.2 months vs. 19.2 months, 40.1% vs. 19.1%, P=0.027). A total of 87 patients (58.8%) developed tumor progression. There were 50 (33.8%), 23 (15.5%) and 39 (26.4%) patients developed local, regional recurrence and distant metastases, respectively. Eleven patients (7.4%) underwent salvage surgery, and the laryngeal preservation rate for entire group was 93.9%. Conclusions: Definitive radiotherapy is an effective treatment for cervical esophageal carcinoma with the advantage of larynx preservation. Local recurrence is the major failure pattern. EQD(2)>66 Gy is associated with the improved overall survival.

Non-Classic Radiation-Induced Liver Disease after Intensity-Modulated Radiotherapy for Hepatocellular Carcinoma with Child–Pugh Grade B

<h3>Purpose/Objective(s)</h3> While the incidence of classic radiation-induced liver disease (cRILD) has been significantly reduced, non-classic radiation-induced liver disease (ncRILD) is still considered as the major limitation that affects the efficacy of radiotherapy (RT) for hepatocellular carcinoma (HCC) patients at present. The purpose of this study was to evaluate the incidence of ncRILD following intensity-modulated radiotherapy (IMRT) in HCC patients with Child–Pugh grade B and establish the nomogram for ncRILD predication. <h3>Materials/Methods</h3> Between September 2014 and July 2021, a total of 75 HCC patients with Child–Pugh grade B treated by IMRT were included. Treatment-related hepatotoxicity was evaluated within 3-month post to the completing RT. In this study, nomogram model was formulated to predict probability of ncRILD in univariate and multivariate analysis. <h3>Results</h3> ncRILD occurred in 17 patients (22.7%). Two of the patients (2.7%) had ≥ G3 transaminase elevation, 14 (18.7%) had a Child–Pugh score increase ≥ 2, and the remaining patient (1.3%) had ≥ G3 transaminase elevation and simultaneous Child–Pugh score increase ≥ 2. No cases of cRILD were observed. A mean dose ≥ 15.1 Gy to the normal liver for ncRILD was the cut-off. Multivariate analysis revealed that prothrombin time before IMRT, tumor number, and mean dose to the normal liver were independent risk factors for ncRILD. The nomogram based on these risk factors displayed exceptional prediction performance (AUC = 0.800, 95% CI, 0.674-0.926). <h3>Conclusion</h3> The incidence of ncRILD following IMRT for HCC patients with Child–Pugh grade B was acceptable. The nomogram based on prothrombin time before RT, tumor number and mean dose to the normal liver showed accurate prediction for the probability of ncRILD in these patients.

Radiotherapy for Advanced Upper Tract Urothelial Carcinoma Intolerant to Chemotherapy

<h3>Purpose/Objective(s)</h3> To retrospectively investigate the safety and effectiveness of radiotherapy for advanced upper tract urothelial carcinoma (UTUC) intolerant to chemotherapy. <h3>Materials/Methods</h3> 20 patients with advanced UTUC who were not able to tolerate chemotherapy were retrospectively collected. All patients were treated with conventionally fractionated radiotherapy (50-67.6Gy/20-33f) or partial-SABR boost to the lesions (50-60Gy/20-25f with tumor center boosted with 6-8Gy/f, 3-5f) for bulky tumors. 2 patients underwent immunotherapy therapy. <h3>Results</h3> The median age was 77 years (range, 58-87 years). All patients underwent primary tumor resection, and no patients underwent metastatic resection. 17 (85%) enrolled patients were oligometastatic (1 to 5 metastases) at diagnosis. 18 (90%) received irradiation to all tumor lesions. Lymph node metastasis was predominant in the whole group (17/20). And other lesions were distributed in local recurrence (6/20), bone metastases (2/20) and abdominal wall/muscle (2/20). The median follow-up time is 38.5 months (range, 4.0-102.2 months). The local control rate (LRFS), progression-free survival rate (PFS) and overall survival rate (OS) of the whole group at 1 years were 90%, 48.9% and 84.4%, respectively. And at 3 years, LRFS, PFS and OS were 65.6%, 27.9% and 43%, respectively. Acutely, 13 patients developed mild gastrointestinal toxicity, generally of grade 1–2. And 7 patients developed acute grade 1–2 hematological toxicity, consisting mainly of anemia and leukopenia. In addition, no grade 3 or higher acute or late toxicities were observed. <h3>Conclusion</h3> For patients with advanced UTUC who were not able to tolerate chemotherapy, radiotherapy is a safe treatment and can achieve good local tumor control.

Preliminary Evaluation of Postoperative Radiotherapy between Small T-Shaped Field and All Regional Lymph Nodes Field in Thoracic Esophageal Squamous Cell Carcinoma

<h3>Purpose/Objective(s)</h3> The optimal extent of clinical target volume (CTV) for postoperative radiotherapy in complete resection thoracic esophageal squamous cell carcinoma (ESCC) patients remains controversial. This study aimed to evaluate the preliminary results of postoperative radiotherapy with standard all regional lymph nodes field and adjusted small T-shaped field. <h3>Materials/Methods</h3> A total of 75 thoracic ESCC patients were enrolled from April 2017 to March 2021, retrospectively. Among them were 63 males and 12 females, with an average age of 64.28 (range, 49-82) years. All patients received intensity-modulated radiotherapy (IMRT) at a dose of 45-50.4Gy/25-28F after radical resection of esophageal carcinoma, of which 39 cases were small T-shaped field (including bilateral supraclavicular lymph nodes, upper and middle mediastinal lymph nodes, small T group),36 cases were all regional lymph nodes field (including tumor bed, bilateral supraclavicular lymph nodes, all mediastinal lymph nodes, left gastric lymph nodes and celiac lymph nodes, control group). 24 cases (32%) received concurrent chemotherapy and 57 cases (76%) received adjuvant chemotherapy. The median follow-up period was 31(range, 15-57) months. <h3>Results</h3> At the end of follow-up period, 7 (17.9%) cases had locoregional recurrence (LRR) and 8(20.5%) had distant metastasis (DM) in small T group, while 9 (25%) cases had LRR and 9 (25%) had DM in control group. There was no significant difference in LRR rate (p=0.456) and DM rate (p=0.643) between the two groups. There was also no significant difference in the total OS rate between the two groups (p=0.146). In terms of radiotherapy parameters, in small T group, the median values of V5, V20 and average dose of the lungs were 37.31%, 16.43% and 8.11Gy, respectively. The median value of the maximum dose of spinal cord was 29.95Gy. For the heart, the median value of the average dose and V30 were 5.13Gy and 2.64%. And the median value of V40 of the stomach was 34.32%. In control group, the median values of V5, V20 and average dose of the lungs were 53.49%, 22.08% and 11.41Gy. The median value of the maximum dose of spinal cord was 36Gy. For the heart, the median value of the average dose and V30 were 27.52Gy and 37.39%. And the median value of V40 of the stomach was 63%. All of the above parameters in small T group were significantly lower than those in control group (p<0.05). In addition, we observed grade 2 radiation pneumonitis and grade 2 radiation esophagitis in both groups:9 cases of radiation pneumonia with grade 2 or above in control group and only 1 case in small T group (p<0.001). There were 15 cases of radiation esophagitis with grade 2 or above in control group and 6 cases in small T group (p=0.024). <h3>Conclusion</h3> In conclusion, radiotherapy with small T-shaped field might be a feasible and efficacious postoperative approach for ESCC patients.

Bone Only Oligometastatic Renal Cell Carcinoma Patients Treated with Stereotactic Body Radiotherapy: A MULTI-Institutional Study

<h3>Purpose/Objective(s)</h3> Previous studies demonstrated the efficacy of stereotactic-body radiotherapy (SBRT) for oligometastatic renal cell carcinoma (RCC) patients. However, it has not been well-studied in patients with bone-only metastatic RCC. This study aimed to analyze the prognostic factors associated with overall survival (OS) and progression-free survival (PFS) in patients with bone-only metastatic RCC who have five or fewer lesions treated with SBRT. <h3>Materials/Methods</h3> The clinical data of 54 patients with 70 bone metastases undergoing SBRT treated between 2013 and 2020 with a fraction dose of at least 6 Gy per fraction, and a biologically effective dose (BED) of at least 90 Gy was retrospectively evaluated. The prognostic factors associated with OS and PFS were assessed. <h3>Results</h3> The majority of lesions were located in the spine (57.4%), and had only one metastasis (64.8%). The median SBRT fraction and total doses were 10 Gy (range: 6–18 Gy) and 20 Gy (range: 12–40 Gy), and SBRT was administered with a median fraction of 3 (range, 1–5). The median BED of SBRT was 108.4 Gy (range: 90.0–202.2 Gy). After a median follow-up of 22.4 months, the 1- and 2-year OS rates were 84.6% and 67.3%, respectively, and median OS was 43.1 months. The 1- and 2-year PFS rate, and median PFS were 63.0%, 38.9%, and 15.3 months, respectively. After completion of metastasis-directed treatment (MDT), disease progression occurred in 26 patients (48.1%) at a median of 12.7 months (IQR 7.1–29.9 months). There were 22 (84.6%) with distant metastasis, one (3.8%) with in-field local recurrence, and three (11.6%) with both distant metastasis and local recurrence. In SBRT-treated lesions, only 4 patients (7.4%) experienced local recurrence, and the 1- and 2-year LC rates per lesion were 94.9% and 92.0% per lesion. Age, metastasis localization, and number of fractions for SBRT were significant prognostic factors for OS in univariate analysis. In multivariate analysis, patients with spine metastasis had a better OS [HR=3.1 (95% CI, 1.3–7.7; p = 0.001)] compared to their counterparts, and patients who received single fraction SBRT [HR=2.2 (95%, 1.2–4.2; p = 0.01)] had a better PFS than those who did not. No patient experienced acute or late toxicities of grade 3 or greater. <h3>Conclusion</h3> To the best of our knowledge, this is the first multicenter study of bone-only oligometastatic RCC patients treated with SBRT. Despite excellent LC at the oligometastatic site treated with SBRT, disease progression was observed in nearly half of patients 13 months after MDT, particularly as distant disease progression other than treated lesion, necessitating an effective systemic treatment to improve treatment outcomes. Prospective trials of SBRT for oligometastatic bone sites are warranted because they may shed light on disease control, survival, and quality of life after such therapy.

A Study to Evaluate the Efficacy of Purely Accelerated 6 Fraction-per-Week Radiotherapy in Post-Operative Oral Cavity Squamous Cell Carcinoma

<h3>Purpose/Objective(s)</h3> To determine the efficacy of pure modestly accelerated fractionated radiotherapy (PM-ART) in postoperative setting in patients of squamous cell carcinoma of oral cavity (OCSCC) in terms of Locoregional control (LRC), Overall survival (OS), and Disease-free survival (DFS). <h3>Materials/Methods</h3> 40 post-operative OCSCC patients with one or more high risk features (pT3 or higher, close margins, DOI >10 mm, lymphovascular invasion, perineural invasion, >1 node positive, extra capsular extension) were treated between May 2015 and July 2016 with adjuvant PM-ART alone (60Gy in 30 fractions @ 2Gy per fraction; 6 fractions per week, over 5 weeks by three-dimensional conformal technique on a linear accelerator). Primary endpoint of the present study was to evaluate the efficacy of PM-ART and secondary endpoint was late toxicity assessment. <h3>Results</h3> 40 patients were followed up till July 2021 of which four were lost to follow up. At a Median follow up of 45.5 months (range 4-70 months), 3-year LRC was 75%. Out of 40 patients, 17 patients had expired at the time of analysis of which 3 deaths occurred due to other competing causes after the completion of RT. DFS rate at 3 years was 64.8% and median DFS was 64.2 months; 3-year OS rate was 59%, and median OS was not yet reached. 23 patients were available for evaluation of late toxicity at the time of analysis. Xerostomia and subcutaneous fibrosis were the main late toxicities observed as follows – xerostomia grade 2 in 2 patients (9%), grade 1 in 11 patients (48%), subcutaneous fibrosis grade 2 was seen in 2 patients (9%), and grade 1 in 12 patients (52%). There was no grade 3 or higher late toxicities recorded. <h3>Conclusion</h3> Intensification of treatment by using PM-ART (6 fractions per week) was found to have good locoregional control rates and survival outcomes with acceptable late toxicities and needs to be evaluated in the context of randomized controlled trials to validate the findings.

Prospective Evaluation of the Efficacy of Neoadjuvant Chemotherapy Followed by Hypofractionated Radiotherapy in Inoperable Oral Cavity Squamous Cell Carcinoma

<h3>Purpose/Objective(s)</h3> We aim to evaluate the role of neoadjuvant chemotherapy followed by hypofractionated radiotherapy in locally advanced unresectable OCSCC in terms of acute toxicity and efficacy. <h3>Materials/Methods</h3> 10 patients with locally advanced (T4a-T4b and N0 or N1-N2) inoperable OCSCC with good performance status were recruited in this single arm prospective study between December 2020-january 2022. All patients received 2 cycles of NACT (paclitaxel 175 mg /m² on D-1, cisplatin 75 mg / m² on D1 and D2 in divided doses) every three weekly followed by Hypofractionated Radiotherapy (RT), delivered by 3-dimensional conformal radiotherapy plan with a dose of 55Gray (Gy) in 22 fractions at 2.5Gy per fraction delivered 5 days a week in two phases. Acute toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and response was evaluated by WHO response criteria. The primary and secondary endpoints were clinical response rate and acute toxicity, respectively. Statistical analysis was done using statistical software. <h3>Results</h3> All patients received 2 cycles of NACT. Median RT dose was 55Gy. overall treatment time (OTT) was 98 days (95-120). Median Duration of follow up was 10 months (8-13 months). Patients' characteristics are summarized in table 1. All the patients completed their treatment as per protocol. Weekly assessment of toxicity was done and recorded during radiotherapy. Patients having dysphagia (grade >2) was 40% (4) and patients having dysphagia (grade ≤ 2) was 60% (6). Patients having oral mucositis (grade >2) was 50% (5) and those having (grade ≤ 2) was 50% (5). Radiation dermatitis more than grade 2 was not observed in any patient. No patient developed grade-4 radiation toxicity. All patients were regularly followed up for response assessment both clinically and radiologically. At median follow up of 10 month, 20% (2) patients had complete response (CR), 70% (7) patients had partial response (PR) and 10% (1) had progressive disease (PD). <h3>Conclusion</h3> Neoadjuvant chemotherapy followed by hypofractionated radiotherapy in locally advanced unresectable OCSCC shows acceptable acute radiation toxicity and good efficacy.

Early Prediction Model of Radiation-Induced Xerostomia Based on Radiomics during Radiotherapy for Nasopharyngeal Carcinoma

<h3>Purpose/Objective(s)</h3> Radiation-induced xerostomia remains one of common side effects for radiotherapy (RT) of nasopharyngeal carcinoma (NPC) and severely affects the quality of life. Early prediction of xerostomia is extremely important, but few studies mention it. We aim to build the early prediction model of xerostomia based on radiomics during RT by artificial intelligence for NPC patients. <h3>Materials/Methods</h3> Seventy-five pathologically confirmed squamous NPC patients were prospectively enrolled in our institution. All patients received a total radiation dose of 66 to 70Gy in 33 fractions at 5 fractions per week using Image-guided intensity modulated radiotherapy (IGRT). The patients received 3-5 cycles of cisplatin-based chemotherapy. MR images with T2-weighted (T2WI), contrast-enhanced T1-weighted (CE-T1WI) and diffusion-weighted imaging (DWI) (b = 0, 500, 800 s/mm²) were acquired on 3.0T MRI. RTOG criteria was used to evaluate xerostomia at 3 months after the completion of radiation. Delivered radiation dose of bilateral parotid and submandibular glands, MR images were collected at pre-RT, 5^th, 15^th fractions and immediately post-RT, respectively. Bilateral parotid and submandibular glands were delineated as the regions of interest (ROI) on CE-T1WI, T2WI, and DWI. We extracted a variety of features from all the images, and selected the optimal features combination by variance analysis. We built the prediction model by support vector machine (SVM). Receiver-operating characteristic (ROC) curve was used to evaluate predictive performance. <h3>Results</h3> The average age was 44.88 years (23-79 years). 24 were female and 51 were male. The mean ADC values of parotid and submandibular glands increased gradually during radiotherapy. Furthermore, the mean ADC values of salivary glands began to increase at 5^th fractions with minimal volume change. For xerostomia, 34 patients with G3-5 were categorized as toxicity cases, and 41 patients with G0-2 were classified as non-toxicity cases. Based on radiomics, clinical characteristics (sex, age, 8^th TNM staging) and radiation dose, we built 15 prediction models. Among them, the best prediction model consists of radiation dose, clinical parameters and ΔRF (the delta-radiomics features from pre-RT to 5^th fractions) which includes 6 ipsilateral parotid features, 8 contralateral parotid features, 7 ipsilateral submandibular features, and 7 contralateral submandibular features. The area under ROC curve is 0.7641, with a precision of 0.7444, a sensitivity of 0.7238, and a specificity of 0.8424. <h3>Conclusion</h3> Early prediction model including delta-radiomics, radiation dose, and clinical parameters exhibits superior sensitivity and specificity. This is an effective model for predicting xerostomia during the early stage of RT, and the clinicians could use it to adjust the treatment strategy and reduce the damage to salivary glands.

Outcomes of Multiple/All lesions Stereotactic Ablative Radiation Therapy (SABR) for Oligo-Metastatic Renal Cancer

<h3>Purpose/Objective(s)</h3> To retrospectively investigate the efficacy and prognostic factors of multiple/all lesions stereotactic ablative radiotherapy (SABR) for oligometastatic renal carcinoma (RCC). <h3>Materials/Methods</h3> The present study retrospectively reviewed thirty-five patients with oligometastatic RCC (1-5 metastases) who received stereotactic ablative radiotherapy (SABR) between April 2015 and December 2020. All patients were treated with SABR (6-10Gy/f, 5 or 10f) or partial-SABR boost to the lesions (40-60Gy/20-25f with tumor center boosted with 6-8Gy/f, 3-5f) for bulky tumors or tumors adjacent to critical organs. 31 patients underwent systematic therapy. Daily CBCT image guidance was used for each patient. Thirty-one patients underwent targeted therapy or targeted plus immunotherapy. <h3>Results</h3> 35 patients with 8 primary lesions and 92 metastatic lesions were included in this study. The median follow-up time was 17.0 months (range 6.1-75.4 months). The average age of all patients was 63 years. Clear cell renal cell carcinoma accounted for 77.1% of all RCC cases. Four patients (11.4%) had sarcomatoid differentiation. 78.5% of the patients had an intermediate or poor IMDC risk. Surgery on primary or metastatic sites was previously performed in 85.7% patients. The median time interval from first distant metastasis radiation therapy (DM-RT) was 7.2 months (range 0 to 50.2 months). Of the patients, 19 were treated for all primary and/or metastatic lesions. Forty percent of the patients received RT before tyrosine kinase inhibitor (TKI) failure. Of the 48 irradiated lesions, 15 received SABR, and 33 received partial-SABR. The local control rate (LRFS), progression-free survival rate (PFS) and overall survival rate (OS) of the whole group at 1 and 3 years were 78% and 78% and 41.8% and 27.9% and 78.3% and 48.2%, respectively. Univariate analysis showed that OS benefit were found in patients who received radiation before tyrosine kinase inhibitor (TKI) failure (p = 0.006) and a short time interval (<6 months) to radiotherapy (p = 0.046). Similar results were also found in PFS in patients who received radiation before TKI failure (p = 0.049) or within 8 months (p = 0.047). There were certain differences in PFS (P = 0.033) between patients receiving radiotherapy to all lesion and those to selected tumors. In multivariate analysis, OS benefits were found in patients who received SABR before TKI failure (p = 0.028). There were certain differences in PFS (P =0.033) between patients receiving radiotherapy to all lesion and those to selected tumors. In multivariate analysis, OS benefits were found in patients who received radiotherapy before TKI failure (p = 0.028), but there was no significant difference in relation to other characters due to the small sample size. <h3>Conclusion</h3> Early use of SABR and all sites irradiation may improve survival. Partial-SABR for bulky lesions close to critical organs could be safely and effectively applied under certain circumstances.

Impact of Mandated Online Prescription Drug Monitoring Programs on Opiate Analgesic Use and Patient-Reported Pain during Radiotherapy for Oropharyngeal Cancer

<h3>Purpose/Objective(s)</h3> Owing to the dramatic rise in opiate-related deaths, the use of online prescription drug monitoring programs (PDMPs) concurrent with new laws restricting opiate administration has become commonplace across the U.S. Some oncologists, however, have expressed concerns that they may unintentionally limit treatment access to at-risk oncology populations. As opiates are frequently used in the acute management strategies for those undergoing radiotherapy for squamous cell carcinoma of the oropharynx, we sought to evaluate changes in short-term opiate prescription use following the implementation of mandated use of an online PDMP in an outpatient radiation oncology practice. <h3>Materials/Methods</h3> Between July of 2017 and December of 2019, 64 patients with biopsy-confirmed oropharyngeal squamous cell carcinoma undergoing curative-intent radiotherapy were evaluated and divided into two cohorts: (1) 26 patients treated 1 year before and (2) 38 patients treated 1.5 years following mandated PDMP use and implementation of new opiate prescription laws. The primary endpoint was opiate prescriptions during therapy and within 3 months after therapy as well as patient-reported pain per the Defense and Veterans Pain Rating Scale. Opiate doses were treated as the response in a series of chi-square tests using a three-level format: no vs. 40 to 3000 vs. 3000+ MME. Cochran-Mantel-Haenszel chi-square analysis with the row mean score test statistic assessed any proportional shifts in dose rates between strata of selected prognostic factors. <h3>Results</h3> The median total opiate doses were 975 MME and 1025 MME in the pre- and postintervention groups with no significant differences in MMEs prescribed (p=0.8441). There was also no difference in patient-reported uncontrolled pain (p=0.38) between the treatment cohorts. Univariate analysis showed tonsillar/soft-palate subsite (p<0.01) and alcohol use (p=0.04) were associated with higher rates of prescribed opioids. While 75% of patients (n=48) received opiates during their acute care, 78% (n=50) were off all prescription narcotics by 3 months or sooner following treatment. <h3>Conclusion</h3> Although potential concerns that mandated PDMP use would affect opiate utilization, there was no associated change in total opiate use by MME for the management of acute pain during radiotherapy for patients with oropharyngeal squamous cell carcinoma nor differences in patient-reported uncontrolled pain. Furthermore, despite high utilization of opiates during radiotherapy, few patients continued use past 3 months after treatment.

The role of PET/CT in radiotherapy for nasopharyngeal carcinoma.

Radiotherapy has already been developed as the standard of care for patients with nasopharyngeal carcinoma (NPC), and precision staging, target volume delineation, prognosis prediction, and post-treatment surveillance are essential in the management of NPC. Positron emission tomography/computed tomography (PET/CT) is increasingly recognized as an imaging modality to guide precision radiotherapy in these areas. The feasibility and efficacy of 18F-FDG PET/CT have been confirmed in tumor diagnosis, treatment planning, prognosis, surveillance, and assessment. Coupled with the capability of revealing tumor metabolic information, 18F-FDG PET/CT is more accurate in identifying primary lesions and metastases of NPC than other conventional imaging methods including CT and MRI and shows the independently diagnostic and prognostic value for radiotherapy. However, 18F-FDG has limitations due to its physiological distribution in brain tissue and increasing uptake in post-radiation inflammation. Novel PET radiotracers including FAPI, NaF, CHO, and FLT are explored as alternatives with potential superiority for radiotherapy in NPC. In this review, we summarized the evolving role of PET/CT in the management of radiotherapy in NPC patients, aiming to facilitate precision radiotherapy from a molecular imaging aspect.

Stereotactic Body Radiotherapy for Renal Cell Carcinoma in Patients with Von Hippel-Lindau Disease-Results of a Prospective Trial.

Simple SummaryClear cell renal cell carcinoma (ccRCC) frequently occurs in patients with von Hippel–Lindau disease and is a leading cause of mortality in patients with this hereditary disorder. Partial nephrectomy, which is the standard treatment, is often complicated by multilocular tumor occurrence in both kidneys requiring repeated surgeries. Consequently, nephron-sparing resections become increasingly difficult ultimately leading to chronic kidney failure. In these patients or in patients who refuse surgery, alternative treatment approaches are needed. In this study, we investigated the outcome and toxicities especially for the kidney after stereotactic body radiotherapy (SBRT). We could demonstrate that SBRT in this highly vulnerable group of patients is feasible without any high-grade adverse events in the long-term and results in excellent local control at the site of treatment. Efficacy of SBRT is already proven for other anatomic sites and it could represent a valuable, non-invasive treatment option for ccRCC as well, especially for patients who are extremely vulnerable to any kidney injury. Further prospective trials evaluating SBRT for localized ccRCC are necessary to verify the promising findings and to examine its role as an alternative to surgery in inoperable patients.Von Hippel–Lindau disease (VHL) is a hereditary disorder associated with malignant tumors including clear cell renal cell carcinoma (ccRCC). Partial nephrectomy is complicated by multilocular tumor occurrence and a high recurrence rate. The aim of this study was to evaluate the potential of stereotactic body radiotherapy (SBRT) as an alternative treatment approach in VHL patients with multiple ccRCC. Patients with VHL and a diagnosis of ccRCC were enrolled. SBRT was conducted using five fractions of 10 Gy or eight fractions of 7.5 Gy. The primary endpoint was local control (LC). Secondary endpoints included alteration of renal function and adverse events. Seven patients with a total of eight treated lesions were enrolled. Median age was 44 years. Five patients exhibited multiple bilateral kidney cysts in addition to ccRCC. Three patients underwent at least one partial nephrectomy in the past. After a median follow-up of 43 months, 2-year LC was 100%, while 2-year CSS, 2-year PFS and 2-year OS was 100%, 85.7% and 85.7%, respectively. SBRT was very well tolerated with no acute or chronic toxicities grade ≥ 2. Mean estimated glomerular filtration rate (eGFR) at baseline was 83.7 ± 13.0 mL/min/1.73 m2, which decreased to 76.6 ± 8.0 mL/min/1.73 m2 after 1 year. Although the sample size was small, SBRT resulted in an excellent LC rate and was very well tolerated with preservation of kidney function in patients with multiple renal lesions and cysts.

Effects of dose and dose-averaged linear energy transfer on pelvic insufficiency fractures after carbon-ion radiotherapy for uterine carcinoma

Background and PurposeThe correlation between dose-averaged linear energy transfer (LETd) and its therapeutic or adverse effects, especially in carbon-ion radiotherapy (CIRT), remains controversial. This study aimed to investigate the effects of LETd and dose on pelvic insufficiency fractures after CIRT. Material and MethodsAmong patients who underwent CIRT for uterine carcinoma, 101 who were followed up for > 6 months without any other therapy were retrospectively analyzed. The sacrum insufficiency fractures (SIFs) were graded according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer toxicity criteria. The correlations between the relative biological effectiveness (RBE)-weighted dose, LETd, physical dose, clinical factors, and SIFs were evaluated. In addition, we analyzed the association of SIF with LETd, physical dose, and clinical factors in cases where the sacrum D50% RBE-weighted dose was above the median dose. ResultsAt the last follow-up, 19 patients developed SIFs. Receiver operating characteristic curve analysis revealed that the sacrum D50% RBE-weighted dose was a valuable predictor of SIF. Univariate analyses suggested that LETd V10 keV/µm, physical dose V5 Gy, and smoking status were associated with SIF. Cox regression analysis in patients over 50 years of age validated that current smoking habit was the sole risk factor for SIF. Therefore, LETd or physical dose parameters were not associated with SIF prediction. ConclusionThe sacrum D50% RBE-weighted dose was identified as a risk factor for SIF. Additionally, neither LETd nor physical dose parameters were associated with SIF prediction.

MiR-302a-3p Promotes Radiotherapy Sensitivity of Hepatocellular Carcinoma by Regulating Cell Cycle via MCL1.

Background The relationship between tumor suppressor gene miR-302a-3p and radiotherapy for hepatocellular carcinoma (HCC) remains unclear. This study intended to illustrate the molecular mechanism how miR-302a-3p regulated radiotherapy sensitivity of HCC. Methods miR-302a-3p expression in HCC tissues and cells was examined by qRT-PCR. The effect of miR-302a-3p on HCC radiotherapy sensitivity were detected by CCK-8, colony formation, and flow cytometry assays. The expression levels of cell cycle-related proteins were detected by Western blot. The influence of miR-302a-3p on radiotherapy sensitivity of HCC was further investigated via cell cycle inhibitor (Caudatin) treatment. The target gene (MCL1) of miR-302a-3p was obtained by bioinformatics analysis, and their binding relationship was confirmed by RNA-binding protein immunoprecipitation assay. The mechanisms of miR-302a-3p regulating cell cycle and affecting radiotherapy sensitivity of HCC cells through MCL1 were further explored through the rescue experiments. Results miR-302a-3p expression was remarkably reduced in radiotherapy-resistant tissues and cells of HCC. miR-302a-3p overexpression restored sensitivity of radiotherapy-resistant HCC cells to radiotherapy. Treatment with cell cycle inhibitor Caudatin could reverse suppressive effect of miR-302a-3p downregulation on sensitivity of HCC to radiotherapy. Additionally, miR-302a-3p could restrain MCL1 expression. In vitro cell assays further revealed that miR-302a-3p/MCL1 axis could enhance radiotherapy sensitivity of HCC cells by inducing G0/G1 arrest. Conclusions miR-302a-3p facilitated radiotherapy sensitivity of HCC cells by regulating cell cycle via MCL1, which provided a new underlying target for radiotherapy resistance of HCC patients.

Preliminary clinical effect evaluation of digital head and neck radiotherapy oral positioning stents

Objective: To develop a designing software of digital oral positioning stent for radiotherapy of head and neck, and to compare its clinical effect with traditional oral positioning stents made by lost wax process. Methods: Thirty patients with nasopharyngeal cancer who received oral examination before radiotherapy in the prosthodontics department from July to December, 2021, were selected and divided into three groups according to the patients' wishes, 10 per group: one group without radiotherapy oral positioning stents, one group with traditional oral positioning stents (traditional stents group), and the third group with digital oral positioning stents (digital stents group). Patients' ages range from 20 years old to 71 years old. There were 15 males and 15 females involved in this study. The manufacturing time and comfort of the two positioning stents were evaluated, and the radiation doses of the radiotherapy target areas and surrounding healthy tissues were statistically analyzed at the end of radiotherapy. Results: The manufacturing time of digital stents group [(209±7) min] was much less than that of traditional stents group [(490±10) min] (t=69.85, P<0.001). The comfort of patients' wearing of digital stents [first wearing: 5 (3, 6) score; at the end of radiotherapy: 4 (3, 5) score] was better than that of traditional ones [first wearing: 7 (3, 7) score; at the end of radiotherapy: 7 (3, 7) score] (U=22.00, P=0.033; U=20.50, P=0.023). There was no significant differences in the target radiation doses among the three groups, and the radiation doses of tongue [traditional stents group: (36.74±5.45) Gy; digital stents group: (35.96±4.98) Gy] and mandible [traditional stents group: (35.46±4.19) Gy; digital stents group: (35.34±3.98) Gy] were significantly lower in the patients wearing oral positioning stents than in the patients without oral positioning stents [tongue: (41.49±4.46) Gy; madible: (39.32±3.52) Gy] (P<0.05). Conclusions: Oral positioning stents for nasopharyngeal carcinoma radiotherapy could greatly reduce the exposure doses of tongue and madible of patients. Digital oral positioning stents designed and manufactured by independently developed software had higher production efficiency than the traditional method, and patients' evaluation of comfort was better.

The Prognostic Value of Postoperative Radiotherapy for Thymoma and Thymic Carcinoma: A Propensity-Matched Study Based on SEER Database.

Simple SummaryAlthough surgery has been recognized as the cornerstone of treatment for patients with resectable thymic epithelial tumors, the role of postoperative radiotherapy remains controversial. We performed this SEER-based propensity-matched analysis to investigate the prognostic value of postoperative radiotherapy in thymoma and thymic carcinoma. The results showed that postoperative radiotherapy improved both overall survival and cancer-specific survival in patients with Masaoka-Koga stage IIB–IV thymoma. This study is the first to demonstrate the prognostic value of postoperative radiotherapy in stage IIB thymic carcinoma. This large, up-to-date population-based longitudinal study may provide guidance on the use of postoperative radiotherapy for a thymoma or thymic carcinoma.(1) Objectives: The effect of postoperative radiotherapy (PORT) for thymoma and thymic carcinoma remains controversial. This study aimed to investigate the prognostic value of PORT for thymoma and thymic carcinoma in a population-based registry. (2) Methods: This retrospective study used the Surveillance, Epidemiology, and End Results (SEER) database to identify patients diagnosed with thymoma and thymic carcinoma between 2010 and 2019. Propensity score matching was performed to adjust statistical influences between the PORT and non-PORT groups. (3) Results: A total of 2558 patients with thymoma (n = 2138) or thymic carcinoma (n = 420) were included. In the multivariate analysis, PORT was an independent prognostic factor for OS (overall survival; p < 0.001) and CSS (cancer-specific survival; p = 0.001) in thymoma and an independent prognostic factor for OS in thymic carcinoma (p = 0.018). Subgroup analyses revealed that PORT was beneficial to OS and CSS in patients with Masaoka-Koga stage IIB-IV thymoma (OS: IIB, p < 0.001; III-IV, p = 0.005; CSS: IIB, p = 0.015; III-IV, p = 0.002) and stage IIB thymic carcinoma (OS: p = 0.012; CSS: p = 0.029). (4) Conclusion: This propensity-matched analysis identified the prognostic value of PORT in thymoma and thymic carcinoma based on the SEER database. For patients with stage IIB-IV thymoma and stage IIB thymic carcinoma, PORT was associated with improved OS and CSS. A more positive attitude towards the use of PORT for nonlocalized thymoma and thymic carcinoma may be appropriate.

The Efficacy of Radiotherapy without Surgery for External Auditory Canal Squamous Cell Carcinoma.

External auditory canal (EAC) cancer is a rare disease for which there are no adequate evidence-based treatment strategies. Radiotherapy is often used as the initial treatment to preserve the organ. This study aimed to elucidate the efficacy of radiotherapy for EAC squamous cell carcinoma (SCC). Patients with T1 disease were treated with radiotherapy alone. Patients with T2–4 disease were treated with chemoradiotherapy. The median follow-up period was 30.4 months. The 3-year local control (LC) rate for all patients was 51%, the disease-free survival (DFS) rate was 44%, and the overall survival (OS) rate was 73%. For T1–3 disease, the 3-year LC rate was 74%, DFS was 62%, and OS was 89%. However, for T4 disease, the 3-year LC rate was 17%, DFS was 17%, and OS was 50%. In a univariate analysis, only the T-category was a significant factor for LC and DFS (p = 0.006 and 0.02, respectively). All local recurrences were within the high-dose irradiated area. The results of this study suggest chemoradiotherapy can be an alternative to a combination of surgery and postoperative radiation for T1–3 SCC of the EAC. However, the efficacy of chemoradiotherapy in T4 cases was inadequate.