Longitudinal post-radiotherapy plasma Epstein-Barr virus DNA trends inform on optimal risk stratification in endemic nasopharyngeal carcinoma.

OBJECTIVES: To characterize longitudinal changes in Epstein-Barr virus (EBV) DNA post-radiotherapy in nasopharyngeal carcinoma (NPC) patients, and investigate whether an early (0-2 weeks) or delayed (8-12 weeks) EBV DNA result better predicts for disease-free survival (DFS). MATERIALS AND METHODS: Histologically-confirmed NPC patients with ≥1 EBV DNA test quantified using the harmonized BamHI-W polymerase chain reaction-based assay at 0-2 and 8-12 weeks post-radiotherapy were included. RESULTS: We identified 302 patients with EBV DNA measured at 0-2 weeks post-radiotherapy; of which, 110 (36.4 %) underwent a repeat test at 8-12 weeks post-treatment. Patients harboring a detectable EBV DNA at 0-2 weeks experienced an inferior DFS (adjusted HR1-264 copies 1.72 [95 %CI: 1.05-2.83], P = 0.031; AHR≥265 copies 4.39 [95 %CI: 1.68-11.44], P = 0.002 relative to 0 copies/mL). At 8-12 weeks, we observed substantial shifts in EBV DNA readings from 0 to 2 weeks; 76/110 (69.1 %) and 34/110 (30.9 %) patients at 0-2 weeks versus 90/110 (81.8 %) and 20/110 (18.2 %) at 8-12 weeks recorded undetectable and detectable EBV DNA, respectively. Positive EBV DNA at 8-12 weeks was strongly associated with relapse (73.3 % [11/15] for 1-264; 80.0 % [4/5] for ≥265 subgroups had relapses versus 15.6 % [14/90] for 0 copies/mL). Area under receiver operating curve values for 2-year relapse rates were 0.817 (95 %CI: 0.725-0.909) for stage + EBV DNA8-12w versus 0.654 (95 %CI: 0.542-0.765) for stage + EBV DNA0-2w. CONCLUSION: EBV DNA is dynamic post-radiotherapy, and delayed EBV DNA testing better enriched for higher-risk NPC patients. This implicates trials investigating adjuvant chemotherapy intensification based on early EBV DNA testing.

The impact of the COVID-19 pandemic on nasopharyngeal carcinoma patients - a national cancer centre experience.

Purpose or objective: The COVID-19 pandemic has resulted in significant healthcare implications, with care for cancer patients compromised due to resource diversion towards battling the pandemic. We aim to investigate the impact of the peak wave of the pandemic in 2020 on the delivery of cancer care in Singapore, specifically via our nasopharyngeal carcinoma (NPC) treatment data. This study applies real world numbers to the impact of COVID-19 on cancer care delivery in Singapore. The choice of nasopharyngeal cancer allows a good direct estimate of common treatment measures such as time to biopsy, time to staging scans, time to treatment commencement, due to its clear protocol and algorithms for staging and treatment; thus serving as an excellent surrogate for the effectiveness and timeliness of the different aspects of cancer care delivery. Materials and methods: In this retrospective study, we included all patients with newly diagnosed NPC from 1st January to 31st May from 2017 to 2020 at our centre. This time period was chosen as it coincided with the period in 2020 during the COVID-19 pandemic where there was the most strain on healthcare resources and the most restrictions on population movement within Singapore, which may impact on healthcare seeking behaviour. Narrowing down the time period to the first 5 months of the 4 respective years also allowed us to reduce the effect of annual seasonal variation in patient numbers seen as a result of holidays and festive periods such as the Lunar New Year and scheduled school holidays. Electronic medical records (EMR) were accessed. Only newly diagnosed NPC cases were included in our analysis. Patients with second synchronous primary malignancies or NPC disease recurrence were excluded. Data analysis was carried out using a combination of SPSS and Microsoft Excel. Results: Significantly, there was a reduction of 37-46.3% in newly diagnosed NPC cases during the peak of the COVID-19 pandemic from January to end May 2020 compared to the preceding three years. Despite the reduction in numbers of newly diagnosed NPC, there was no statistically significant differences in delay from biopsy to the first radiation oncology visit and from biopsy to the first day of treatment in 2020 compared to the preceding years. All the patients treated in our centre also received the standard NPC treatment for their disease stage as per international guidelines. Conclusion: We recommend a heightened awareness of the dangers of delaying cancer presentation and care in healthcare policies and resource allocation and at the same time, encourage patient's confidence in their ability to seek care. With the resurgence of new COVID-19 variants and case numbers worldwide and in Singapore, this study focuses upon the need to be aware of the exigencies of other clinical groups in resource utilization. It would be instructive to compare this study with future long term follow up to investigate the trajectory of our cancer care delivery, as well as survival outcomes.

18F-FMISO PET-guided dose escalation with multifield optimization intensity-modulated proton therapy in nasopharyngeal carcinoma.

PURPOSE: The purpose of this study was to evaluate the radiotherapy planning feasibility of dose escalation with intensity-modulated proton therapy (IMPT) to hypoxic tumor regions identified on 18F-Fluoromisonidazole (FMISO) positron emission tomography and computed tomography (PET-CT) in NPC. MATERIALS AND METHODS: Nine patients with stages T3-4N0-3M0 NPC underwent 18F-FMISO PET-CT before and during week 3 of radiotherapy. The hypoxic volume (GTVhypo) is automatically generated by applying a subthresholding algorithm within the gross tumor volume (GTV) with a tumor to muscle standardized uptake value (SUV) ratio of 1.3 on the 18F-FMISO PET-CT scan. Two proton plans were generated for each patient, a standard plan to 70 Gy and dose escalation plan with upfront boost followed by standard 70GyE plan. The stereotactic boost was planned with single-field uniform dose optimization using two fields to deliver 10 GyE in two fractions to GTVhypo. The standard plan was generated with IMPT with robust optimization to deliver 70GyE, 60GyE in 33 fractions using simultaneous integrated boost technique. A plan sum was generated for assessment. RESULTS: Eight of nine patients showed tumor hypoxia on the baseline 18F-FMISO PET-CT scan. The mean hypoxic tumor volume was 3.9 cm3 (range .9-11.9cm3 ). The average SUVmax of the hypoxic volume was 2.2 (range 1.44-2.98). All the dose-volume parameters met the planning objectives for target coverage. Dose escalation was not feasible in three of eight patients as the D0.03cc of temporal lobe was greater than 75GyE. CONCLUSIONS: The utility of boost to the hypoxic volume before standard course of radiotherapy with IMPT is dosimetrically feasible in selected patients. Clinical trials are warranted to determine the clinical outcomes of this approach.

International recommendations for plasma Epstein-Barr virus DNA measurement in nasopharyngeal carcinoma in resource-constrained settings: lessons from the COVID-19 pandemic.

The effects of the COVID-19 pandemic continue to constrain health-care staff and resources worldwide, despite the availability of effective vaccines. Aerosol-generating procedures such as endoscopy, a common investigation tool for nasopharyngeal carcinoma, are recognised as a likely cause of SARS-CoV-2 spread in hospitals. Plasma Epstein-Barr virus (EBV) DNA is considered the most accurate biomarker for the routine management of nasopharyngeal carcinoma. A consensus statement on whether plasma EBV DNA can minimise the need for or replace aerosol-generating procedures, imaging methods, and face-to-face consultations in managing nasopharyngeal carcinoma is urgently needed amid the current pandemic and potentially for future highly contagious airborne diseases or natural disasters. We completed a modified Delphi consensus process of three rounds with 33 international experts in otorhinolaryngology or head and neck surgery, radiation oncology, medical oncology, and clinical oncology with vast experience in managing nasopharyngeal carcinoma, representing 51 international professional societies and national clinical trial groups. These consensus recommendations aim to enhance consistency in clinical practice, reduce ambiguity in delivering care, and offer advice for clinicians worldwide who work in endemic and non-endemic regions of nasopharyngeal carcinoma, in the context of COVID-19 and other airborne pandemics, and in future unexpected settings of severe resource constraints and insufficiency of personal protective equipment.

Efficacy and safety of apatinib in recurrent/metastatic nasopharyngeal carcinoma: A pilot study.

BACKGROUND: There is no standard-of-care for recurrent, metastatic nasopharyngeal carcinoma (rmNPC) after first-line chemotherapy. Here, we report the efficacy and safety data of apatinib in rmNPC patients. METHODS: Thirty-five biopsy-proven rmNPC patients received apatinib at 500 mg/day under a compassionate access programme. Primary end-point was objective response rate (ORR; RECIST v1.1). Kaplan-meier method was used to estimate progression-free survival (PFS) and overall survival (OS). Toxicity was assessed by CTCAE v4.0. RESULTS: 82.9% (29 of 35) of patients had poly-metastatic rmNPC. All patients, except five, were platinum-refractory; 37.1% (13 of 35) received ≥ 2 lines. Median number of apatinib cycles was 4.0 (IQR: 2.0-8.0). ORR was 31.4% (11 of 35 [95% CI: 16.9-49.3]) and disease control rate was 74.3% (26 of 35 [95% CI: 56.7-87.5]); 11 (31.4%) and 4 (11.4%) patients demonstrated response for ≥ 6 and ≥ 12 months, respectively. Median PFS and OS was 3.9 (95% CI: 3.1-5.5) months and 5.8 (95% CI: 4.5-8.0) months, respectively. Among the ≥ 12-month responders, all patients had pre-apatinib EBV DNA titer of <700 (range: 353-622) copies/ml; this was consistent with the association of PFS with pre-apatinib EBV DNA titer (adjusted HR 3.364 [95% CI: 1.428-7.923] for ≥ 4000 copies/ml, P = 0.006). 42.9% (15 of 35) of patients required dose reduction. Nonetheless, only five (14.3%) patients suffered from G3 toxicities (two haematological, one hypertension, one hand-foot syndrome and one elevated aminotransferases). CONCLUSION: Our data suggests potential efficacy of apatinib in rmNPC patients. Although incidence of severe toxicities was low, dose modification was required in 42.9% of patients.

International Recommendations on Reirradiation by Intensity Modulated Radiation Therapy for Locally Recurrent Nasopharyngeal Carcinoma.

PURPOSE: Reirradiation for locally recurrent nasopharyngeal carcinoma (NPC) is challenging because prior radiation dose delivered in the first course is often close to the tolerance limit of surrounding normal structures. A delicate balance between achieving local salvage and minimizing treatment toxicities is needed. However, high-level evidence is lacking because available reports are mostly retrospective studies on small series of patients. Pragmatic consensus guidelines, based on an extensive literature search and the pooling of opinions by leading specialists, will provide a useful reference to assist decision-making for these difficult decisions. METHODS AND MATERIALS: A thorough review of available literature on recurrent NPC was conducted. A set of questions and preliminary draft guideline was circulated to a panel of international specialists with extensive experience in this field for voting on controversial areas and comments. A refined second proposal, based on a summary of the initial voting and different opinions expressed, was recirculated to the whole panel for review and reconsideration. The current guideline was based on majority voting after repeated iteration for final agreement. RESULTS: The initial round of questions showed variations in clinical practice even among the specialists, reflecting the lack of high-quality supporting data and the difficulties in formulating clinical decisions. Through exchange of comments and iterative revisions, recommendations with high-to-moderate agreement were formulated on general treatment strategies and details of reirradiation (including patient selection, targets contouring, dose prescription, and constraints). CONCLUSION: This paper provides useful reference on radical salvage treatment strategies for recurrent NPC and optimization of reirradiation through review of published evidence and consensus building. However, the final decision by the attending clinician must include full consideration of an individual patient's condition, understanding of the delicate balance between risk and benefits, and acceptance of risk of complications.

Phase II study of nimotuzumab (TheraCim-hR3) concurrent with cisplatin/radiotherapy in patients with locally advanced head and neck squamous cell carcinoma.

BACKGROUND: The efficacy of a combination of nimotuzumab, a humanized monoclonal antibody to the epidermal growth factor receptor, with chemoradiation in locally advanced head and neck squamous cell carcinoma (HNSCC) was evaluated in a phase II study. METHODS: Patients with stage III/IV HNSCC received 3-weekly cisplatin 100 mg/m2 for three cycles and weekly nimotuzumab 200 mg for 8 weeks concurrently with radiotherapy. Primary endpoint was best overall response (BOR) and secondary endpoint was progression-free survival (PFS). RESULTS: Thirty-seven patients were included; the majority were Chinese (76%), male (89%), and had stage IVA/IVB HNSCC (92%). BOR of complete and partial response was seen in 22/37 (59%) and 10/37 (27%) patients, respectively. Median PFS was 17.5 months (95% CI: 11.1-54.5) and 3-year PFS was 40.4% (95% CI: 24.3-55.9). The frequency and type of adverse events observed were similar to standard chemoradiation. CONCLUSION: The combination of nimotuzumab with cisplatin and radiotherapy was safe and achieved high response rates in HNSCC.

Chemotherapy in Combination With Radiotherapy for Definitive-Intent Treatment of Stage II-IVA Nasopharyngeal Carcinoma: CSCO and ASCO Guideline.

PURPOSE: The aim of this joint guideline is to provide evidence-based recommendations to practicing physicians and other healthcare providers on definitive-intent chemoradiotherapy for patients with stage II-IVA nasopharyngeal carcinoma (NPC). METHODS: The Chinese Society of Clinical Oncology (CSCO) and ASCO convened an expert panel of radiation oncology, medical oncology, surgery, and advocacy representatives. The literature search included systematic reviews, meta-analyses, and randomized controlled trials published from 1990 through 2020. Outcomes of interest included survival, distant and locoregional disease control, and quality of life. Expert panel members used this evidence and informal consensus to develop evidence-based guideline recommendations. RESULTS: The literature search identified 108 relevant studies to inform the evidence base for this guideline. Five overarching clinical questions were addressed, which included subquestions on radiotherapy (RT), chemotherapy sequence, and concurrent, induction, and adjuvant chemotherapy options. RECOMMENDATIONS: Evidence-based recommendations were developed to address aspects of care related to chemotherapy in combination with RT for the definitive-intent treatment of stage II to IVA NPC.Additional information is available at www.asco.org/head-neck-cancer-guidelines.

Monocytic Myeloid-Derived Suppressor Cells Underpin Resistance to Adoptive T Cell Therapy in Nasopharyngeal Carcinoma.

Advanced, late-stage Epstein-Barr virus (EBV)-positive nasopharyngeal carcinoma (NPC) is incurable, and its treatment remains a clinical and therapeutic challenge. Results from a phase II clinical trial in advanced NPC patients employing a combined chemotherapy and EBV-specific T cell (EBVST) immunotherapy regimen showed a response rate of 71.4%. Longitudinal analysis of patient samples showed that an increase in EBV DNA plasma concentrations and the peripheral monocyte-to-lymphocyte ratio negatively correlated with overall survival. These parameters were combined into a multivariate analysis to stratify patients according to risk of death. Immunophenotyping at serial time points showed that low-risk individuals displayed significantly decreased amounts of monocytic myeloid-derived suppressor cells postchemotherapy, which subsequently influenced successful cytotoxic T-lymphocyte (CTL) immunotherapy. Examination of the low-risk group, 2 weeks post-EBVST infusion, showed that individuals with a greater overall survival possessed an increased frequency of CD8 central and effector memory T cells, together with higher levels of plasma interferon (IFN)-γ, and cytotoxic lymphocyte-associated transcripts. These results highlight the importance of the rational selection of chemotherapeutic agents and consideration of their impact on both systemic immune responses and downstream cellular immunotherapy outcomes.

Lactate dehydrogenase kinetics predict chemotherapy response in recurrent metastatic nasopharyngeal carcinoma.

BACKGROUND: Lactate dehydrogenase (LDH) is a known prognostic biomarker for the endemic variant of nasopharyngeal carcinoma (NPC). Here, we investigate whether serial changes in LDH level between chemotherapy (CT) cycles are associated with tumour response to CT. METHODS: Patients with biopsy-proven, recurrent or treatment-naïve metastatic NPC (mNPC) were recruited. All patients had received at least two cycles of platinum-based doublet or triplet CT, with serial assessment of LDH prior to every cycle of chemotherapy (CT1-6). Patients harbouring conditions that affect LDH levels (IU/L) were excluded. Tumour response was assessed after every two cycles of CT by RECIST v1.1. RESULTS: A total of 158 patients were analysed, including 77 with recurrent and 81 with treatment-naïve mNPC. High pre-CT LDH was associated with an inferior overall survival [hazard ratio 1.93 for ⩾240 versus <240 (1.34-2.77), p < 0.001], which is consistent with published literature. We found that both absolute LDH levels and LDH ratios (LDHCTn: LDHCTn-1) were associated with tumour response [partial response versus progressive disease: median value across CT1-6 = 168-190 versus 222-398 (absolute); 0.738-0.988 versus 1.039-1.406 (ratio)], albeit LDH ratio had a tighter variance between patients. Finally, we showed that an LDH ratio cut-off of 1.0 at CT1, CT3 and CT5 was predictive of progressive disease at CT2, CT4, CT6 [area under the curve of 0.73 (0.65-0.80)]. CONCLUSION: Herein, we characterised the longitudinal variation of LDH in response to CT in mNPC. Our findings suggest the potential utility of interval LDH ratio to predict subsequent tumour response to CT.

High-Dimensional Characterization of the Systemic Immune Landscape Informs on Synergism Between Radiation Therapy and Immune Checkpoint Blockade.

PURPOSE: Improved antitumor responses have been observed in patients after combination radiation therapy (RT) and immune checkpoint blockade (ICB). Whether these clinical responses are linked to the host systemic immune system has not been elucidated. METHODS AND MATERIALS: In this single-institution prospective observational study, peripheral blood was longitudinally collected from 10 patients with metastatic disease who had responded to anti-PD-1/anti-PD-L1 ICB and received RT (8-50 Gy in 1-5 fractions) upon disease progression at the following timepoints: baseline (pre-RT), 1 to 2 weeks post-RT, and post-ICB (cycle 1) on reintroduction post-RT. To thoroughly characterize the interaction between combined RT-ICB and the host immune system, we performed high-dimensional, mass cytometry-based immunophenotyping of circulating lymphocytes using a 40-marker panel addressing lineage, differentiation, activation, trafficking, cytotoxicity, and costimulatory and inhibitory functions. Phenotypic expression of circulating lymphocytes was compared across patients and time points and correlated with post-RT tumor responses. RESULTS: Foremost, we demonstrated excellent posttreatment clinical responses, including 4 local responses with >50% reduction in radiated tumor size, 1 out-of-field response, and 4 patients who resumed ICB for >1 year. Baseline and post-RT immune states were highly heterogeneous among patients. Despite this interindividual heterogeneity in baseline immune states, we observed a systemic immune reaction to RT-ICB common across patients, histology, and radiation sites; a subset of pre-existing Ki-67+ CD8+ T cells were increased post-RT and further expanded upon reintroduction of ICB post-RT (2.3-fold increase, P = .02). Importantly, RT did not alter the phenotypic profile of these Ki-67+ CD8+ T cells, which was characterized by a distinct activated and differentiated effector phenotype. CONCLUSIONS: Collectively, these findings point toward a sustained reinvigoration of host antitumor immunity after RT-ICB and suggest an expansion in activated Ki-67+ CD8+ T cells as a possible demonstration of this synergy, thereby providing new insights that may support the development of optimal sequencing strategies.

A Prospective 10-Year Observational Study of Reduction of Radiation Therapy Clinical Target Volume and Dose in Early-Stage Nasopharyngeal Carcinoma.

PURPOSE: Current guideline recommends a uniform method of delineation of subclinical disease within the primary clinical target volume (CTVp) for all stages of nasopharyngeal carcinoma (NPC). We performed a prospective observational study to investigate the outcomes with a reduced CTVp and radiation dose for early-stage NPC. METHODS AND MATERIALS: Patients with newly diagnosed, biopsy-proven World Health Organization type II-III and American Joint Committee on Cancer/Union for International Cancer Control sixth edition stage T1-2N0-1 disease were enrolled. All patients were treated with intensity modulated radiation therapy alone. We categorized CTVp into CTVp1 (high risk) and CTVp2 (low risk). CTVp1 comprised of gross tumor (on magnetic resonance imaging or contrast-enhanced computed tomography) plus a 5-mm margin (3-mm posteriorly) and was prescribed to 60 Gy in 30 fractions (fr). CTVp2 was generated from CTVp1 plus a 5-mm margin (3 mm posteriorly), excluding the maxillary and cavernous sinuses, and was prescribed to 54 Gy in 30 fr. The prescribed doses to the primary and nodal gross tumor volume (GTVp and GTVn) were 68 Gy in 30 fr and 60 to 66 Gy in 30 fr, respectively. Primary endpoint was local recurrence-free survival. This study was registered in ClinicalTrials.gov, number NCT03839602. RESULTS: From May 2001 to August 2006, 103 patients were recruited and completed IMRT. With a median follow-up of 15.2 years (range, 2.1-18.1 years), only 1 patient had local failure. Ten-year local recurrence-free survival, regional recurrence-free survival, distant metastasis-free survival, and overall survival were 90.3%, 88.3%, 90.3%, and 91.2%, respectively. Among late IMRT-related adverse events, we recorded 2 patients with G1 cranial nerve injury, 3 patients with G3 hearing loss, and 3 patients with G3 subcutaneous fibrosis. No patients had temporal lobe necrosis, brain stem injury, or trismus. CONCLUSIONS: Decreased CTV margins and radiation doses can achieve long-term tumor control with mild late toxicities for patients with early-stage NPC.

Comparison of radiomics tools for image analyses and clinical prediction in nasopharyngeal carcinoma.

OBJECTIVE: Radiomics pipelines have been developed to extract novel information from radiological images, which may help in phenotypic profiling of tumours that would correlate to prognosis. Here, we compared two publicly available pipelines for radiomics analyses on head and neck CT and MRI in nasopharynx cancer (NPC). METHODS AND MATERIALS: 100 biopsy-proven NPC cases stratified by T- and N-categories were enrolled in this study. Two radiomics pipeline, Moddicom (v. 0.51) and Pyradiomics (v. 2.1.2) were used to extract radiomics features of CT and MRI. Segmentation of primary gross tumour volume was performed using Velocity v. 4.0 by consensus agreement between three radiation oncologists. Intraclass correlation between common features of the two pipelines was analysed by Spearman's rank correlation. Unsupervised hierarchical clustering was used to determine association between radiomics features and clinical parameters. RESULTS: We observed a high proportion of correlated features in the CT data set, but not for MRI; 76.1% (51 of 67 common between Moddicom and Pyradiomics) of CT features and 28.6% (20 of 70 common) of MRI features were significantly correlated. Of these, 100% were shape-related for both CT and MRI, 100 and 23.5% were first-order-related, 61.9 and 19.0% were texture-related, respectively. This interpipeline heterogeneity affected the downstream clustering with known prognostic clinical parameters of cTN-status and GTVp. Nonetheless, shape features were the most reproducible predictors of clinical parameters among the different radiomics modules. CONCLUSION: Here, we highlighted significant heterogeneity between two publicly available radiomics pipelines that could affect the downstream association with prognostic clinical factors in NPC. ADVANCES IN KNOWLEDGE: The present study emphasized the broader importance of selecting stable radiomics features for disease phenotyping, and it is necessary prior to any investigation of multicentre imaging datasets to validate the stability of CT-related radiomics features for clinical prognostication.

International Guideline on Dose Prioritization and Acceptance Criteria in Radiation Therapy Planning for Nasopharyngeal Carcinoma.

PURPOSE: The treatment of nasopharyngeal carcinoma requires high radiation doses. The balance of the risks of local recurrence owing to inadequate tumor coverage versus the potential damage to the adjacent organs at risk (OARs) is of critical importance. With advancements in technology, high target conformality is possible. Nonetheless, to achieve the best possible dose distribution, optimal setting of dose targets and dose prioritization for tumor volumes and various OARs is fundamental. Radiation doses should always be guided by the As Low As Reasonably Practicable principle. There are marked variations in practice. This study aimed to develop a guideline to serve as a global practical reference. METHODS AND MATERIALS: A literature search on dose tolerances and normal-tissue complications after treatment for nasopharyngeal carcinoma was conducted. In addition, published guidelines and protocols on dose prioritization and constraints were reviewed. A text document and preliminary set of variants was circulated to a panel of international experts with publications or extensive experience in the field. An anonymized voting process was conducted to rank the proposed variants. A summary of the initial voting and different opinions expressed by members were then recirculated to the whole panel for review and reconsideration. Based on the comments of the panel, a refined second proposal was recirculated to the same panel. The current guideline was based on majority voting after repeated iteration for final agreement. RESULTS: Variation in opinion among international experts was repeatedly iterated to develop a guideline describing appropriate dose prioritization and constraints. The percentage of final agreement on the recommended parameters and alternative views is shown. The rationale for the recommendations and the limitations of current evidence are discussed. CONCLUSIONS: Through this comprehensive review of available evidence and interactive exchange of vast experience by international experts, a guideline was developed to provide a practical reference for setting dose prioritization and acceptance criteria for tumor volumes and OARs. The final decision on the treatment prescription should be based on the individual clinical situation and the patient's acceptance of optimal balance of risk.

Clinical and dosimetric predictors of physician and patient reported xerostomia following intensity modulated radiotherapy for nasopharyngeal cancer - A prospective cohort analysis.

BACKGROUND AND PURPOSE: To compare physician and patient reported xerostomia and correlate xerostomia with dosimetric and clinical parameters for nasopharyngeal cancer (NPC) patients treated with intensity modulated radiotherapy (IMRT) and chemotherapy. PATIENTS AND METHODS: We analyzed the data of 172 patients with locally advanced NPC. Xerostomia was evaluated via physician-rated xerostomia based on RTOG morbidity score (E1), patient-rated dry mouth (E2) and patient-rated sticky saliva (E3) based on EORTC QLQ-HN35 questionnaire. Primary endpoint was the presence of moderate to severe xerostomia at 2-year after completion of IMRT. RESULTS: The levels of physician reported xerostomia (E1) were consistently lower than patient reported dry mouth (E2) over time. The incidence of patients with xerostomia at 3-month post RT was 58% based on E1, 70% based on E2, and 51% based on E3. The corresponding incidence rates at 2-year post RT was 26% (E1), 36% (E2) and 21% (E3). The incidence of patients with xerostomia at 1-year post RT was close to that at 2-year post RT for all the 3 endpoints. The average Dmean of parotid glands was 41.5 Gy (range: 31.0 Gy-65.9 Gy, median: 40.7 Gy). No dosimetric parameters were significantly associated with xerostomia. CONCLUSION: Significant proportion of patients still experienced long term xerostomia with IMRT. Dose-effect relationships between xerostomia and the parotid glands were not observed in this study.

Deep Learning for Automated Contouring of Primary Tumor Volumes by MRI for Nasopharyngeal Carcinoma.

Background Nasopharyngeal carcinoma (NPC) may be cured with radiation therapy. Tumor proximity to critical structures demands accuracy in tumor delineation to avoid toxicities from radiation therapy; however, tumor target contouring for head and neck radiation therapy is labor intensive and highly variable among radiation oncologists. Purpose To construct and validate an artificial intelligence (AI) contouring tool to automate primary gross tumor volume (GTV) contouring in patients with NPC. Materials and Methods In this retrospective study, MRI data sets covering the nasopharynx from 1021 patients (median age, 47 years; 751 male, 270 female) with NPC between September 2016 and September 2017 were collected and divided into training, validation, and testing cohorts of 715, 103, and 203 patients, respectively. GTV contours were delineated for 1021 patients and were defined by consensus of two experts. A three-dimensional convolutional neural network was applied to 818 training and validation MRI data sets to construct the AI tool, which was tested in 203 independent MRI data sets. Next, the AI tool was compared against eight qualified radiation oncologists in a multicenter evaluation by using a random sample of 20 test MRI examinations. The Wilcoxon matched-pairs signed rank test was used to compare the difference of Dice similarity coefficient (DSC) of pre- versus post-AI assistance. Results The AI-generated contours demonstrated a high level of accuracy when compared with ground truth contours at testing in 203 patients (DSC, 0.79; 2.0-mm difference in average surface distance). In multicenter evaluation, AI assistance improved contouring accuracy (five of eight oncologists had a higher median DSC after AI assistance; average median DSC, 0.74 vs 0.78; P < .001), reduced intra- and interobserver variation (by 36.4% and 54.5%, respectively), and reduced contouring time (by 39.4%). Conclusion The AI contouring tool improved primary gross tumor contouring accuracy of nasopharyngeal carcinoma, which could have a positive impact on tumor control and patient survival. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Chang in this issue.