Multimodality radiomics for tumor prognosis in nasopharyngeal carcinoma.

BACKGROUND: The prognosis of nasopharyngeal carcinoma (NPC) is challenging due to late-stage identification and frequently undetectable Epstein-Barr virus (EBV) DNA. Incorporating radiomic features, which quantify tumor characteristics from imaging, may enhance prognosis assessment. PURPOSE: To investigate the predictive power of radiomic features on overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) in NPC. MATERIALS AND METHODS: A retrospective analysis of 183 NPC patients treated with chemoradiotherapy from 2010 to 2019 was conducted. All patients were followed for at least three years. The pretreatment CT images with contrast medium, MR images (T1W and T2W), as well as gross tumor volume (GTV) contours, were used to extract radiomic features using PyRadiomics v.2.0. Robust and efficient radiomic features were chosen using the intraclass correlation test and univariate Cox proportional hazard regression analysis. They were then combined with clinical data including age, gender, tumor stage, and EBV DNA level for prognostic evaluation using Cox proportional hazard regression models with recursive feature elimination (RFE) and were optimized using 20 repetitions of a five-fold cross-validation scheme. RESULTS: Integrating radiomics with clinical data significantly enhanced the predictive power, yielding a C-index of 0.788 ± 0.066 to 0.848 ± 0.079 for the combined model versus 0.745 ± 0.082 to 0.766 ± 0.083 for clinical data alone (p<0.05). Multimodality radiomics combined with clinical data offered the highest performance. Despite the absence of EBV DNA, radiomics integration significantly improved survival predictions (C-index ranging from 0.770 ± 0.070 to 0.831 ± 0.083 in combined model versus 0.727 ± 0.084 to 0.734 ± 0.088 in clinical model, p<0.05). CONCLUSIONS: The combination of multimodality radiomic features from CT and MR images could offer superior predictive performance for OS, PFS, and DMFS compared to relying on conventional clinical data alone.

A multivariable normal tissue complication probability model for predicting radiation-induced hypothyroidism in nasopharyngeal carcinoma patients in the modern radiotherapy era.

Radiation-induced hypothyroidism (RHT) is a common long-term complication for nasopharyngeal carcinoma (NPC) survivors. A model using clinical and dosimetric factors for predicting risk of RHT could suggest a proper dose-volume parameters for the treatment planning in an individual level. We aim to develop a multivariable normal tissue complication probability (NTCP) model for RHT in NPC patients after intensity-modulated radiotherapy or volumetric modulated arc therapy. The model was developed using retrospective clinical data and dose-volume data of the thyroid and pituitary gland based on a standard backward stepwise multivariable logistic regression analysis and was then internally validated using 10-fold cross-validation. The final NTCP model consisted of age, pretreatment thyroid-stimulating hormone and mean thyroid dose. The model performance was good with an area under the receiver operating characteristic curve of 0.749 on an internal (200 patients) and 0.812 on an external (25 patients) validation. The mean thyroid dose at ≤45 Gy was suggested for treatment plan, owing to an RHT incidence of 2% versus 61% in the >45 Gy group.

Improved prediction of radiation-induced hypothyroidism in nasopharyngeal carcinoma using pre-treatment CT radiomics.

When planning radiation therapy, late effects due to the treatment should be considered. One of the most common complications of head and neck radiation therapy is hypothyroidism. Although clinical and dosimetric data are routinely used to assess the risk of hypothyroidism after radiation, the outcome is still unsatisfactory. Medical imaging can provide additional information that improves the prediction of hypothyroidism. In this study, pre-treatment computed tomography (CT) radiomics features of the thyroid gland were combined with clinical and dosimetric data from 220 participants to predict the occurrence of hypothyroidism within 2 years after radiation therapy. The findings demonstrated that the addition of CT radiomics consistently and significantly improves upon conventional model, achieving the highest area under the receiver operating characteristic curve (AUCs) of 0.81 ± 0.06 with a random forest model. Hence, pre-treatment thyroid CT imaging provides useful information that have the potential to improve the ability to predict hypothyroidism after nasopharyngeal radiation therapy.

Safety and Immunogenicity of Homologous and Heterologous Adenoviral-Vectored and mRNA COVID-19 Vaccine Regimens in Radiotherapy Patients.

Diminished immune response after vaccination occurs in cancer patients. This observational study evaluated the immune response and safety profile after COVID-19 vaccination in radiotherapy patients. The study comprised 53 cancer patients undergoing radiotherapy and voluntarily received the COVID-19 vaccine. The two regimens were homologous ChAdOx1-S recombinant (AstraZeneca, AZ), "AZ-AZ" and heterologous "AZ-mRNA". The seroconversion rate and anti-RBD immunoglobulin geometric mean titers (GMT) were assessed and compared with healthy controls. Adverse effects were assessed using a questionnaire. The seroconversion rate was 52.4% 1 month after the first dose with GMT 4.3 U/mL (95%CI 1.4-13). Following the second dose, the AZ-AZ group achieved 95% seroconversion rate with GMT = 188.4 U/mL (95%CI 67.1-529), which was significantly lower than the healthy cohort, GMT = 945 U/mL (95%CI 708-1261). Cancer patients in AZ-mRNA group achieved a 100% seroconversion rate with a high GMT = 1400.8 U/mL (95%CI 429.5-4566), which was significantly lower than the healthy cohort, GMT = 5169.9 U/mL (95%CI 3582.2-7461.5). Most adverse effects were mild. Our findings suggest that radiotherapy patients had fair immunogenicity after the first dose, but achieved a high seroconversion rate after the second dose with manageable adverse effects. However, their immunologic response was lower than in healthy individuals, indicating that other preventive strategies are needed.

A prospective randomized study comparing the efficacy between povidone-iodine gargling and benzydamine hydrochloride for mucositis prevention in head and neck cancer patients receiving concurrent chemoradiotherapy.

Background: Concurrent chemoradiation (CCRT) has been the standard treatment for organ preservation or locally advanced head and neck cancer (LAHNC). Radiation-induced oral mucositis (RIOM) is an important treatment-limiting toxicity. Benzydamine hydrochloride was recommended to prevent oral mucositis. Povidone-iodine had also been adopted to use as an oral rinse to prevent mucositis. Objective: This study compared the efficacy between benzydamine hydrochloride and 0.1% povidone-iodine to prevent RIOM in HNC patients who received concurrent chemoradiotherapy. Methods: We conducted a randomized control study in HNC patients receiving CCRT with curative intent. The stratification factors were primary site of disease, treatment modality, chemotherapy regimen, and schedule. The primary outcome was RIOM assessed by Oral Mucositis Assessment Scale (OMAS). Secondary outcomes included RIOM assessed by NCI-CTCAE, use of analgesic, antibiotics and anti-fungal drugs, hospitalization, and participant satisfaction. Results: There were 83 participants recruited for this study with 71 completing the trial. Demographic characteristics were well-balanced between both arms. The univariate regression analysis revealed that povidone-iodine correlated with less RIOM compared to benzydamine hydrochloride (coefficient -2.25, 95% CI -4.37 to -0.012, p-value 0.03). The incidence of grade III-IV CTCAE RIOM during the study period was 51.4% with benzydamine hydrochloride compared to 26.5% with 0.1% povidone iodine (p-value 0.032). The peak incidence of grade III-IV CTCAE RIOM occurred in the 7th week of treatment (40.5% vs. 11.8%, p-value 0.01). This indicated the efficacy of povidone-iodine to prevent severe RIOM which usually most severity in the last week of CCRT treatment. The multivariate analysis revealed that the CCRT setting (definitive vs. adjuvant) and gargling agents (povidone-iodine vs. benzydamine hydrochloride were the factors associated with RIOM. Conclusion: This study demonstrated higher efficacy of 0.1% povidone-iodine gargle than benzydamine hydrochloride in mucositis prevention.

Digital fabrication of customized intraoral appliances for head and neck radiotherapy.

Introduction: The radiotherapy received by head and neck cancer patients commonly has adverse effects on oral tissue and the muscles of mastication. This short communication describes the digital fabrication of intraoral appliances for radiotherapy and muscle exercises. Methods: Three patients diagnosed with tongue squamous carcinoma were treatment-planned for radiotherapy using different radiation techniques. The patients were referred for oral scanning and digital bite records, and the appliance was collaboratively designed by a radiation oncologist, dentist, and laboratory technician. The appliance covered the occlusal surface of the remaining teeth with a 1-mm engagement. The lingual plate was 2-mm below the occlusal plane, and extended 4-mm distally, and the jaws were opened by 20-mm. The appliances were printed overnight using a rigid and biocompatible 3D printing material. Results: Requiring minimal chair-time, the appliance was easily inserted and adjusted to comfortably fit in the mouth. The patients were trained to insert it themselves. The tongue was at a pre-determined position during daily radiotherapy, and the healthy tissues were separated from the radiation field. The patients had mild adverse effects on their oral mucosa. Additionally, the appliances were used for muscle exercises after the radiation courses to prevent trismus. Conclusions: The interprofessional collaboration to fabricate customized intraoral appliances using digital workflow to maximize patients' benefits is feasible. Clinical significance: The use of intraoral appliances is potentially increased when the fabrication process is facilitated. Using an intraoral appliance precisely targets the tumor are for better treatment outcomes, and the healthy adjacent tissues will be preserved to maintain the patient's quality of life.

Trehalose versus carboxymethylcellulose oral spray for relieving radiation-induced xerostomia in head and neck cancer patients: a randomized controlled trial.

BACKGROUND: The aim of this study was to investigate the effect of trehalose oral spray to relieve radiation-induced xerostomia on a randomized controlled trial (RCT). METHODS: Prior to RCT, the effect of trehalose (5-20%) on the epithelial growth of fetal mouse salivary gland (SG) explants was evaluated to confirm if 10% trehalose exerted the best epithelial outcomes. Participants who completed radiotherapy for head and neck cancer (HNC) treatment were enrolled in a double-blind RCT, according to inclusion and exclusion criteria as per the CONSORT statement. The experimental group (n = 35) received 10% trehalose spray, while the control group (n = 35) received carboxymethylcellulose (CMC) spray to apply intra-orally 4 times/day for 14 days. Salivary pH and unstimulated salivary flow rate were recorded pre- and post-interventions. The Xerostomia-related Quality of Life scale (XeQoLs) was filled, and scores assessed post-interventions. RESULTS: In the SG explant model, pro-acinar epithelial growth and mitosis was supported by 10% topical trehalose. As for RCT outcomes, salivary pH and unstimulated salivary flow rate were significantly improved after use of 10% trehalose spray when compared to CMC (p < 0.05). Participants reported an improvement of XeQoLs dimension scores after using trehalose or CMC oral sprays in terms of physical, pain/discomfort, and psychological dimensions (p < 0.05), but not social (p > 0.05). When comparing between CMC and trehalose sprays, XeQoLs total scores were not statistically different (p > 0.05). CONCLUSIONS: The 10% trehalose spray improved salivary pH, unstimulated salivary flow rate, and the quality-of-life dimensions linked with physical, pain/discomfort, and psychological signs. The clinical efficacy of 10% trehalose spray was equivalent with CMC-based saliva substitutes for relieving radiation-induced xerostomia; therefore, trehalose may be suggested in alternative to CMC-based oral spray.(Thai Clinical Trials Registry; https://www.thaiclinicaltrials.org/ TCTR20190817004).

The Prognostic Predictors of Airway Stenting in Malignant Airway Involvement From Esophageal Carcinoma.

BACKGROUND: In locoregional esophageal carcinoma (EC), airway involvement is the most common route of extraesophageal metastasis. The prognosis remains poor even with a multimodality approach. Although airway stenting is well known for restoration of the airway, the survival benefit is still lacking. METHODS: A total of 37 of patients with airway involvement from EC who underwent airway stenting at a single institution from 2015 to 2020 were retrospectively reviewed. Survival curves after stent placement among different groups were analyzed using Kaplan-Meier method. RESULTS: Of 37 patients, 34 were male, and the mean age was 58.9 years (42 to 80). EC was commonly located at midesophagus (51.4%). The site of airway involvement was left main bronchus (48.6%), trachea (32.4%), multiple sites (16.2%), and right main bronchus (2.7%). The nature of airway involvement was tumor invasion (91.9%), compression (62.2%), and fistula (37.8%). Twenty-three patients (62.2%) had airway involvement at the time of esophageal cancer diagnosis. Only 4 patients underwent esophageal stenting. The median survival time after stent placement was 97 days (5 to 539). Chemotherapy and/or radiotherapy were given before stent placement in 18 patients (48.6%). Treatment-naive before airway stenting and diagnosis of airway involvement at the same time of EC diagnosis were independent predictors for the increased survival after stent placement ( P <0.05). Poststent treatment was associated with improved survival ( P =0.002). CONCLUSION: In patients with malignant airway involvement from EC who underwent airway stenting, the prognostic predictors for improved survival were treatment-naive status, receiving treatment after airway stenting, and early-onset of airway involvement.

High-dose Intensity-modulated proton therapy versus Standard-dose Intensity-modulated RadIation therapy for esophageal squamous cell carcinoma (HI-SIRI): study protocol for a randomized controlled clinical trial.

BACKGROUND: Chemoradiotherapy is the standard of care for esophageal cancer as a neoadjuvant treatment before surgery, or as a definitive treatment for unresectable disease. Intensity-modulated radiotherapy (IMRT) has been considered the standard radiation technique. However, patients suffer from treatment-related toxicities, and most die from disease progression or recurrence. With emerging technological advancement, proton therapy has theoretical advantages over IMRT because it offers apparent dosimetric benefits to allow dose escalation to the target while better sparing surrounding tissues such as the lungs, heart, liver, and spinal cord. The purpose of this study protocol is to investigate the survival benefit of proton therapy using modern intensity-modulated proton therapy (IMPT) compared to standard IMRT for esophageal cancer. METHODS: This is a two-arm open phase II/III multi-institution randomized controlled trial. Eligible patients will have histologically confirmed squamous cell carcinoma of the thoracic esophagus with no evidence of tracheoesophageal/esophagobronchial fistula or distant metastasis. After stratification according to resectability status (resectable vs. borderline resectable/unresectable), a total of 232 patients will be randomized to receive IMPT or IMRT using a 1:1 allocation ratio. In resectable cases, surgical resection following concurrent chemoradiation will be attempted for the patients who are medically fit at the time of surgery. In those with initially borderline resectable/unresectable disease, definitive concurrent chemoradiation will be performed. The phase II study will assess safety (toxicity and postoperative complications) and feasibility (recruitment rate and chemoradiation dose modification) in 40 patients into each arm. The study will then continue into phase III, further recruit 76 patients into each arm, and compare progression-free survival between IMPT vs IMRT groups. The secondary endpoints will be overall survival, local and distant control, toxicities, health-related quality of life, and cost-utility. This protocol describes a detailed radiotherapy and chemotherapy. DISCUSSION: This randomized clinical trial will demonstrate the clinical benefit of IMPT in esophageal cancer treatment in terms of survival and toxicity outcomes which will further establish high-level evidence for radiation modality in squamous cell carcinoma of the thoracic esophagus. TRIAL REGISTRATION: TCTR20200310006 . Registered 10 March 2020.

Long-term oncological outcomes of hypofractionated versus conventional fractionated whole breast irradiation with simultaneous integrated boost in early-stage breast cancer.

PURPOSE: For patients with early breast cancer who undergo breast-conserving surgery, adjuvant whole breast irradiation (WBI) with simultaneous integrated boost (SIB) results in lower radiotherapy fractions. Published studies have shown that both conventional fraction with SIB (C-SIB) and hypofractionation with SIB (H-SIB) seem to be safe and feasible. In this study, we sought to compare the oncologic outcomes between C-SIB and H-SIB in early-stage breast cancer. MATERIALS AND METHODS: Stage I-II breast cancer patients who received adjuvant WBI with SIB between January 2008 and December 2017 were retrospectively reviewed. The radiation dose in the C-SIB group was 50 Gy and 65 Gy in 25 daily fractions, while in the H-SIB group, it was 43.2 Gy and 52.8 Gy in 16 daily fractions to the whole breast and tumor bed, respectively. RESULTS: A total of 188 patients, 103 in the C-SIB group and 85 in the H-SIB group, were included. With a median follow-up time of 87 months, 7-year locoregional control of C-SIB was comparable to H-SIB (95.8% vs. 97.4%, p = 0.964). The 7-year distant metastasis-free survival rates of C-SIB and H-SIB were 89.9% and 95.9% (p = 0.111), while the 7-year disease-free survival rates were 84.2% and 95.4%, respectively (p = 0.176). In multivariate analysis, there was no significant prognostic factor associated with better overall survival. CONCLUSION: H-SIB provided comparable locoregional control to C-SIB. With the advantage of a shorter radiotherapy course, H-SIB could be a favorable option for WBI in early-stage breast cancer.

Comparison of intensity modulated proton therapy beam configurations for treating thoracic esophageal cancer.

Background and purpose: Specific proton-beam configurations are needed to spare organs at risk (OARs), including lungs, heart, and spinal cord, when treating esophageal squamous cell carcinoma (ESCC) in the thoracic region. This study aimed to propose new intensity-modulated proton therapy (IMPT) beam configurations and to demonstrate the benefit of IMPT compared with intensity-modulated x-ray therapy (IMXT) for treating ESCC. Material and methods: IMPT plans with three different beam angle configurations were generated on CT datasets of 25 ESCC patients that were treated with IMXT. The IMPT beam designs were two commonly-used beam configurations (anteroposterior and posterior oblique) and a recently proposed beam configuration (anterosuperior with posteroinferior). The target doses were 50-54 Gy(RBE) and 60-64 Gy(RBE) to the low-risk and high-risk target volumes, respectively. Robust optimization was applied for the IMPT plans. The differences in the dose-volume parameters between the IMXT and IMPT plans were compared. Results: With target coverage comparable to standard IMXT, IMPT had significantly lower mean doses to the OARs. IMPT with an anteroposterior opposing beam generated the lowest lung dose (mean = 7.1 Gy(RBE), V20 = 14.1%) and the anterosuperior with posteroinferior beam resulted in the lowest heart dose (mean = 12.8 Gy(RBE), V30 = 15.7%) and liver dose (mean = 3.9 Gy(RBE), V30 = 5.9%). For the subgroup of patients with an inferior tumor location (PTVs overlapping a part of the contoured heart), the novel beam demonstrated the optimal OARs sparing. Conclusion: Compared with IMXT, the IMPT plans significantly reduced the radiation dose to the surrounding organs when treating ESCC. IMPT beam configuration selection depends on the tumor location relative to the heart.

Value of Diffusion-Weighted Imaging and Dynamic Contrast-Enhanced Magnetic Resonance Imaging for Prediction of Treatment Outcomes in Nasopharyngeal Carcinoma.

OBJECTIVE: Magnetic resonance imaging (MRI) parameters that reflect the tumor microenvironment of nasopharyngeal carcinoma (NPC) may predict treatment response and facilitate treatment planning. This study aimed to evaluate the diffusion-weighted imaging and dynamic contrast-enhanced MRI (DCE-MRI) values for predicting the treatment outcomes in NPC patients. METHODS: Eighty-three patients with NPC underwent pretreatment MRI simulation with diffusion-weighted imaging and dynamic contrast-enhanced MRI. Average values of the apparent diffusion coefficient (ADC), Ktrans, Kep, Ve, Vp, and tumor volume of the primary tumors were measured. Other potential clinical characteristics (age, sex, staging, pathology, pretreatment Epstein-Barr virus level, and treatment type) were analyzed. Patients underwent follow-up imaging 6 months after treatment initiation. Treatment responses were assigned according to the Response Evaluation Criteria in Solid Tumors guideline (version 1.1). RESULTS: Fifty-one patients showed complete response (CR), whereas 32 patients did not (non-CR). Univariable logistic regression with variables dichotomized by optimal cutoff values showed that ADC ≥1.45 × 10 -3 mm 2 /s, Vp ≥0.14, tumor volume of ≥14.05 mL, high stage (stages III and IV), and Epstein-Barr virus level of ≥2300 copies/mL were predictors of non-CR ( P = 0.008, 0.05, 0.01, 0.009, and 0.04, respectively). The final multivariable model, consisting of a combination of ADC ≥1.45 × 10 -3 mm 2 /s, Vp ≥0.14, and high stage, could predict non-CR with a good discrimination ability (area under the receiver operating characteristic curve, 0.76 [95% confidence interval, 0.66-0.87]; sensitivity, 62.50%; specificity, 80.39%; and accuracy 73.49%). CONCLUSIONS: A multivariable prediction model using a combination of ADC ≥1.45 × 10 -3 mm 2 /s, Vp ≥0.14, and high stage can be effective for treatment response prediction in NPC patients.

Tumor Prognostic Prediction of Nasopharyngeal Carcinoma Using CT-Based Radiomics in Non-Chinese Patients.

PURPOSE: We aimed to construct predictive models for the overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) for nasopharyngeal carcinoma (NPC) patients by using CT-based radiomics. MATERIALS AND METHODS: We collected data from 197 NPC patients. For each patient, radiomic features were extracted from the CT image acquired at pretreatment via PyRadiomics. Feature selection was performed in two steps. First, features with high inter-observer variability based on multiple tumor delineations were excluded. Then, stratified bootstrappings were performed to identify feature combinations that most frequently achieved the highest (i) area under the receiver operating characteristic curve (AUC) for predicting 3-year OS, PFS, and DMFS or (ii) Harrell's C-index for predicting time to event. Finally, regularized logistic regression and Cox proportional hazard models with the most frequently selected feature combinations as input were tuned using cross-validation. Additionally, we examined the robustness of the constructed model to variation in tumor delineation by simulating 100 realizations of radiomic feature values to mimic features extracted from different tumor boundaries. RESULTS: The combined model that used both radiomics and clinical features yielded significantly higher AUC and Harrell's C-index than models using either feature set alone for all outcomes (p < 0.05). The AUCs and Harrell's C-indices of the clinical-only and radiomics-only models ranged from 0.758 ± 0.091 to 0.789 ± 0.082 and from 0.747 ± 0.062 to 0.767 ± 0.074, respectively. In comparison, the combined models achieved AUC of 0.801 ± 0.075 to 0.813 ± 0.078 and Harrell's C-indices of 0.779 ± 0.066 to 0.796 ± 0.069. The results showed that our models were robust to variation in tumor delineation with the coefficient of variation ranging from 4.8% to 6.4% and from 6.7% to 9.3% for AUC and Harrell's C-index, respectively. CONCLUSION: Our results demonstrated that using CT-based radiomic features together with clinical features provided superior NPC prognostic prediction than using either clinical or radiomic features alone.

Dosimetric evaluation of photons versus protons in postmastectomy planning for ultrahypofractionated breast radiotherapy.

BACKGROUND: Ultrahypofractionation can shorten the irradiation period. This study is the first dosimetric investigation comparing ultrahypofractionation using volumetric arc radiation therapy (VMAT) and intensity-modulated proton radiation therapy (IMPT) techniques in postmastectomy treatment planning. MATERIALS AND METHODS: Twenty postmastectomy patients (10-left and 10-right sided) were replanned with both VMAT and IMPT techniques. There were four scenarios: left chest wall, left chest wall including regional nodes, right chest wall, and right chest wall including regional nodes. The prescribed dose was 26 Gy(RBE) in 5 fractions. For VMAT, a 1-cm bolus was added for 2 in 5 fractions. For IMPT, robust optimization was performed on the CTV structure with a 3-mm setup uncertainty and a 3.5% range uncertainty. This study aimed to compare the dosimetric parameters of the PTV, ipsilateral lung, contralateral lung, heart, skin, esophageal, and thyroid doses. RESULTS: The PTV-D95 was kept above 24.7 Gy(RBE) in both VMAT and IMPT plans. The ipsilateral lung mean dose of the IMPT plans was comparable to that of the VMAT plans. In three of four scenarios, the V5 of the ipsilateral lung in IMPT plans was lower than in VMAT plans. The Dmean and V5 of heart dose were reduced by a factor of 4 in the IMPT plans of the left side. For the right side, the Dmean of the heart was less than 1 Gy(RBE) for IMPT, while the VMAT delivered approximately 3 Gy(RBE). The IMPT plans showed a significantly higher skin dose owing to the lack of a skin-sparing effect in the proton beam. The IMPT plans provided lower esophageal and thyroid mean dose. CONCLUSION: Despite the higher skin dose with the proton plan, IMPT significantly reduced the dose to adjacent organs at risk, which might translate into the reduction of late toxicities when compared with the photon plan.

Utility of diffusion-weighted magnetic resonance imaging in predicting the treatment response of nasopharyngeal carcinoma.

OBJECTIVE: Predicting the treatment response in patients with nasopharyngeal carcinoma (NPC) is challenging. This study evaluated the utility of diffusion-weighted imaging (DWI) in predicting the treatment response in patients with NPC. METHODS: We prospectively enrolled 33 patients with newly diagnosed NPC who underwent magnetic resonance imaging with the propeller DWI and apparent diffusion coefficient (ADC) map before and at 5 weeks after chemoradiation. The following ADC values of the primary tumor were calculated: pre-treatment ADC (pre-ADC), pre-treatment ADC ratio (pre-ADC ratio), ADC change (▵ADC), ADC change ratio (▵ADC ratio), and percentage of ADC change (▵%ADC). The correlations between these parameters and treatment outcomes were explored, and the patients were classified as good responders (complete response) and poor responders (stable disease, partial response, or progressive disease) based on the Response Evaluation Criteria in Solid Tumors, version 1.1. RESULTS: The ▵ADC, ▵ADC ratio, and ▵%ADC were significantly lower in the poor-responder group (n = 12) than in the good-responder group (n = 21; p = 0.001, p = 0.002, and p = 0.004, respectively). There was no significant difference between groups in the pre-ADC and pre-ADC ratios (p = 0.602 and p = 0.685, respectively). The optimal ▵ADC, ▵ADC ratio, and ▵%ADC cutoff values for predicting poor response were >0.65 mm2/sec, 0.28, and 60%, respectively (sensitivity: 83.3%, 75%, and 83.3%; specificity: 71.4%, 85.7%, and 71.4%, respectively). CONCLUSION: The ▵ADC, ▵ADC ratio, and ▵%ADC obtained during the pre-treatment and mid-treatment periods could be potential biomarkers for predicting treatment response in patients with NPC.

Cranial neuropathies in advanced nasopharyngeal carcinoma: Neurological recovery after modern radiotherapy and systemic chemotherapy.

OBJECTIVES: Cranial neuropathy is a common presenting symptom of advanced T4 nasopharyngeal carcinoma (NPC). Data on neurological outcomes after modern intensity-modulated radiotherapy (IMRT) and chemotherapy are scarce. MATERIALS AND METHODS: Case records of consecutive T4 NPC patients who received definitive IMRT in two tertiary oncology centers in 2004-2019 were reviewed. Patterns of cranial neuropathies at disease presentation were recorded. Time to neurological recovery and the rate of subsequent re-palsy were estimated by the Kaplan-Meier method. Clinical predictors were analyzed using multivariable Cox regression. RESULTS: During the study period, 257 T4 NPC patients presented with 504 individual cranial neuropathies. The median time from neuropathy onset to NPC diagnosis was two months (IQR, 1-4 months). Cranial nerves (CN) VI (56.4%), V2 (47.9%), and V3 (29.2%) were most frequently involved. At a median follow-up of 6.4 years, the crude partial and full recovery rates of neuropathies were 111 (22%) and 289 (57.3%), respectively. CN III, IV, and VI had the highest 5-year full recovery rate (72.7%), followed by CN V1-3 (60.3%), XII (48.6%), and II (18.2%) (p < 0.001). Positive smoking history, optic nerve involvement, and longer duration of neuropathy were independent negative predictors for neurological recovery. After full recovery, re-palsy was observed in 6.9% (20/289) of the nerves, 60% of which co-occurred with local NPC recurrences. CONCLUSION: Durable recovery of most cranial neuropathies in advanced T4 NPC was observed in the era of modern IMRT and effective systemic chemotherapy. Both patient and disease factors affected the chance of neurological recovery. Re-palsy of recovered nerves should prompt careful evaluation for local recurrence.

Flattening filter free stereotactic body radiation therapy for lung tumors: outcomes and predictive factors.

BACKGROUND: Stereotactic body radiation therapy (SBRT) using flattening filter free (FFF) has been commonly used, however, its outcomes and predictive factors in lung tumors are limiting. Thus, we aim to assess the clinical outcomes of this approach and identify factors associated with outcomes in patients with early stage non-small cell lung cancer (NSCLC) and oligometastatic/oligoprogressive lung tumor (OLT). METHODS: Patients who underwent lung SBRT with FFF were retrospectively reviewed. All patients were delivered using volumetric modulated arc therapy (VMAT) technique. The primary outcome was local control (LC). The secondary outcomes were overall survival (OS) and toxicities. We assessed the association between LC and various factors in OLT. RESULTS: From February 2014 to July 2019, ninety-four patients and 129 lesions with median follow-up time of 30 months were included in the analysis. Twenty-six patients with 26 lesions were early NSCLC, while 68 patients with 103 lesions were OLT, 41.7% of which were from colorectal cancers (CRC) and 18.5% were from primary lung cancers. Two-year LC was 88.9% and 85.7% for early NSCLC and OLT, respectively. Two-year OS was significantly higher for early NSCLC than OLT (83.3% vs. 68.7%, P=0.035). In the multivariate analysis for OLT, CRC origin (hazard ratio, HR 10.59, 95% CI: 2.29-48.95, P=0.003) and gross tumor volume (GTV) mean BED10 ≤147 Gy (HR 5.16, 95% CI: 1.13-23.59, P=0.034) were significantly associated with higher local failure (LF). Most of the acute grade 1-2 toxicities were radiation pneumonitis (26.5%). No grade 3-5 event was observed. CONCLUSIONS: This study confirmed the clinical efficacy and safety of lung SBRT using FFF-technique. Our findings support the role of using a high BED10 regimen to achieve good LC for OLT and the potential role for dose escalation for primary CRC.

Value of dynamic contrast-enhanced magnetic resonance imaging for determining the plasma Epstein-Barr virus status and staging of nasopharyngeal carcinoma.

AIM: To determine the associations between dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) parameters and plasma Epstein-Barr virus (EBV) DNA status and nasopharyngeal carcinoma (NPC) stages. METHODS: We prospectively studied the DCE-MRI results of 47 patients with newly diagnosed NPC and their pre-treatment plasma EBV DNA levels. We recruited all patients who had undergone MRI (1.5 T) simulation at the radiation therapy department of our institute between January 2018-2019. Regions of interest were drawn at primary tumors, and DCE-MRI parameters, including mean values of Ktrans, Kep, Ve, and Vp, were recorded. Spearman's rank correlation was used to identify significant associations between the DCE-MRI parameters and the plasma EBV DNA level and NPC stages. Mann-Whitney U tests and unpaired t-test were performed to compare the DCE-MRI parameters among different groups and to identify optimal cut-off values using receiver operating characteristic curves. RESULTS: We found that the DCE-MRI parameters correlated with the plasma EBV DNA levels and NPC stages. Positive plasma EBV DNA was correlated with lower Kep (optimal cut-off value, 2.1 min-1; area under the curve [AUC], 0.714) and higher Ve (optimal cut-off value, 0.675; AUC, 0.706). Ve higher than 0.765 (AUC, 0.678) was correlated with plasma EBV DNA (≥2300 copies mL-1). Higher Ktrans (cut-off value, 1.495 min-1) was correlated with high-T stage (AUC, 0.767) and high-stage group (AUC, 0.711). CONCLUSIONS: The DCE-MRI parameters are correlated with the plasma EBV DNA status and NPC stages. Therefore, DCE-MRI findings may be used as imaging biomarkers for patients with NPC.

Long-term patient-rated cosmetic and satisfactory outcomes of early breast cancer treated with conventional versus hypofractionated breast irradiation with simultaneous integrated boost technique.

To compare patient-rated cosmetic and satisfactory outcomes between conventional fractionation with simultaneously integrated boost (C-SIB) vs hypofractionation with SIB (H-SIB) in early breast cancer. Patients with stage I and II breast cancer who received breast-conserving surgery followed by radiation with SIB to tumor bed and completed questionnaire were included in this study. Radiotherapy was as follows: C-SIB arm = 50 Gy and 65 Gy in 25 fractions and H-SIB arm = 43.2 Gy and 52.8 Gy in 16 fractions to the whole breast and tumor bed, respectively. Single cross-sectional assessment of the breast cosmesis was done by patients and radiation oncologist at a follow-up visit. Breast cosmetic and satisfaction scores were collected using a four-point Harvard/NSABP/RTOG cosmesis criteria scale and a four-point Likert-type scale, respectively. Of a total of 114 patients (C-SIB = 57) and (H-SIB = 57) arms, a median time from radiotherapy completion to questionnaire response was 7.2 years. Patient-rated cosmetic outcome in C-SIB vs H-SIB was "excellent" in 40.3% vs 45.6%, "good" in 33.3% vs 42.1%, "fair" in 21.1% vs 10.5%, and "poor" in 5.3% vs 1.8% (P = .288). Corresponding satisfaction was "very satisfied" in 52.6% vs 57.9%, "satisfied" in 40.4% vs 35.1%, "neutral" in 7.0% vs 5.2%, and "unsatisfied" in 0% vs 1.8% (P = .683). Stage I and older age at radiotherapy were predictors for favorable (good or excellent) cosmesis and satisfaction, respectively. In early-stage breast cancer, H-SIB provided a trend for better cosmesis than C-SIB while maintaining satisfaction. The reduction in treatment duration and cost as well as favorable cosmesis outcomes encourages the use of H-SIB.

Comparison between the seventh and eighth edition of the AJCC/UICC staging system for nasopharyngeal cancer integrated with pretreatment plasma Epstein-Barr virus DNA level in a non-Chinese population: secondary analysis from a prospective randomized trial.

OBJECTIVE: To validate the eighth edition of the AJCC/UICC staging system in nasopharyngeal cancer (NPC) patients who were uniformly treated in a prospective randomized study using intensity-modulated radiation therapy and to investigate the prognostic value of plasma Epstein-Barr virus (EBV) DNA level when incorporated into the TNM staging. METHODS: Between October 2010 and September 2015, non-metastatic NPC patients were treated with concurrent chemoradiation followed by adjuvant chemotherapy. Pretreatment images of 205 patients were reviewed by two radiologists to determine the TNM classification according to the seventh and eighth editions of the AJCC/UICC staging system. Overall survival (OS), progression-free survival (PFS) and distant metastasis-free survival (DMFS) were calculated. Harrell's C concordance index (C-index) and Akaike information criterion (AIC) were used to compare the staging models. Recursive partitioning analysis (RPA) was conducted and incorporated with plasma EBV DNA. RESULTS: Overall, the eighth edition showed higher C-indexes and lower AIC values in nodal classification and stage groups, indicating a better discrimination performance and better goodness of fit, but showed similar separation for T classification compared with the seventh edition. The integration of pretreatment EBV values (<2300 vs ≥2300 copies/ml) to the eighth edition AJCC/UICC staging system allowed the classification of patients into three RPA categories and further lowered the AIC value and increased the C-index for OS. CONCLUSION: The eighth edition of the AJCC/UICC staging system had higher prognostic values in terms of OS, PFS and DMFS than the previous edition. An integration of pretreatment plasma EBV DNA into the next AJCC/UICC staging could improve the outcome prediction especially in poor risk groups who might benefit from treatment intensification.