Oncologic outcomes after MRI-assisted image-guided brachytherapy with hybrid interstitial and intra-cavitary applicators under moderate sedation for locally advanced cervix cancer.

Purpose: To report outcomes of using image-guided hybrid intra-cavitary/interstitial applicators under moderate sedation for locally advanced cervical cancer patients in our institution. Material and methods: A total of 69 fractions of brachytherapy with hybrid applicators were performed in 33 patients from January 2017 to April 2021. All patients underwent MRI pelvis 1 week pre-brachytherapy to determine suitability for interstitial brachytherapy and pre-plan needle placement. All insertion of applicators were performed under moderate sedation with midazolam and/or fentanyl. Fifty-eight (84.1%) fractions were planned with CT alone. Clinical outcomes, dose volume parameters, and toxicities were analyzed. Results: The median follow-up was 28 months. A total of 320 needles (median, 5 needles per fraction) were implanted, with a median insertion depth of 3 cm (range, 1.5-4 cm). The median high-risk clinical target volume (HR-CTV) during initial brachytherapy was 34.5 cc (range, 17.8-74.7 cc). The median total EQD2 D2cc of the rectum, bladder, sigmoid, and small intestine colon was 71.8 Gy, 81.5 Gy, 69 Gy, and 58.3 Gy, respectively. The 2-year local control and overall survival were 80.7% and 77.7%, respectively. Larger volume HR-CTV was significantly associated with worse local control (HR = 1.08, p = 0.005) and overall survival (HR = 1.04, p = 0.015). None of the patients required in-patient admission or blood transfusion post-procedure. Late grade 3 gastrointestinal and genitourinary toxicities were observed in 4 patients (12.2%). Conclusions: Hybrid applicators inserted under moderate sedation are feasible and safe. Image-guided interstitial brachytherapy with CT planning aided by MRI performed 1 week pre-brachytherapy is associated with favorable outcomes and modest toxicities.

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.

Analysis of Prognostic Factors For External Auditory Canal Carcinoma: A 22-Year Experience.

OBJECTIVE: This study aimed to investigate the prognostic factors and treatment outcomes in patients with the external auditory canal (EAC) squamous cell carcinoma (SCC). METHODS: All patients diagnosed with EAC SCC and treated with curative intent at a single tertiary institution were retrospectively reviewed over a 22-year period. Treatment modalities included surgery with adjuvant treatment or definitive radiotherapy. The primary endpoints were overall survival (OS) and disease-specific survival (DSS). RESULTS: There were 51 patients in our cohort. The 5-year OS and DSS were 64.0% ± 7.0% and 72.0% ± 7.0% respectively. Patients in the surgical arm and RT arm showed no significant difference in OS, DSS, and LRFS (p = 0.075, 0.062, 0.058 respectively). Compared to other routes of spread within the temporal bone, pattern of posterior disease invasion (involving mastoid/sigmoid sinus) showed poorer OS and DSS on multivariate analysis (hazard ratio, HR4.34 and 5.88; p = 0.006 and 0.009). On multivariate analysis, the following factors were independently prognostic of poorer OS and DSS: Previous radiotherapy (HR 3.29 and 4.81, p = 0.021 and p = 0.029); Presence of facial nerve palsy (HR 3.80 and 7.63, p = 0.013 and p = 0.003); Posterior pattern of invasion (HR4.05 and 3.59, p = 0.013 and p = 0.043). Advanced modified Pittsburgh stage was not predictive of poor OS and DSS (HR1.17 and 1.17 E+5, p = 0.786 and p = 0.961). CONCLUSION: Presence of previous radiotherapy, facial nerve palsy and posterior pattern of disease invasion were independent prognostic factors of poorer survival in patients with EAC SCC. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2203-2210, 2023.

Can Radiation Therapy Quality Assurance Improve Nasopharyngeal Cancer Outcomes in Low- and Middle-Income Countries: Reporting the First Phase of a Prospective International Atomic Energy Agency Study.

PURPOSE: Most new nasopharyngeal cancer cases occur in low-income and middle-income countries, and these patients experience poorer overall survival than that of new nasopharyngeal cancer cases in high-income countries. The goal of this research project is to determine whether the introduction of a radiation therapy quality assurance program can ultimately improve outcomes for nasopharyngeal cancer patients in lower-income and middle-income countries. This study reports the results of the first phase of the International Atomic Energy Agency Coordinated Research Project (325-E3-TM-47712). METHODS AND MATERIALS: This prospective study has 2 phases. Phase 1 is a survey of radiation therapy resources, patient characteristics and treatment, and results of radiation therapy quality assurance performed by the expert panel. An educational workshop reviewing phase 1 results for each center was completed before accrual of patients for phase 2. The ultimate aim of the study is to compare the first and second cohort of patients to see if quality assurance can result in fewer major protocol deviations and a 15% improvement in patients' 3-year progression-free survival. RESULTS: Of 14 participating centers, 13 (93%) had computed tomography simulators and linear accelerators (LINAC) with intensity modulated radiation therapy (IMRT) capacity, median 3 LINAC (range, 1-13), and median 10 radiation oncologists (range, 5-51). The annual number of nasopharyngeal cancer cases irradiated was median 54 (range, 10-627). Five of 14 centers (36%) had no local radiation therapy quality assurance. For the current phase 1 study, 134 patients were evaluated, 82.1% had MRI staging, 99.3% had metastatic workup, 65.6% undifferentiated histology, 51% stage 3 and 49% stage 4. Radiation therapy quality assurance revealed 81 (60.4%) of 134 patients had major protocol violations in gross tumor volume and high dose planning target volume contours and/or dosimetry, 28.4% patients had borderline plans, 15 (11.2%) acceptable, and only 6 (4.2%) had inevitable compromise due to tumor extent. CONCLUSIONS: This is the first International Atomic Energy Agency study to address the fundamental issue of treatment quality rather than altered treatment regimens. The high rate of unacceptable radiation therapy plans is a major concern, and we hope phase 2 will show a significant reduction and improved patient outcomes.

Non-anesthetist-administered moderate sedation with midazolam and fentanyl for outpatient MRI-aided hybrid intracavitary and interstitial brachytherapy in cervix cancer: a single-institution experience.

PURPOSE: The aim of the study was to determine the feasibility of interstitial brachytherapy under non-anesthetist-administered moderate sedation, to identify factors influencing the insertion, and the total procedural time. MATERIAL AND METHODS: A total of 47 insertions with hybrid intracavitary and interstitial applicators were performed in 23 patients from March 2017 to March 2020. Moderate sedation was achieved with intravenous midazolam and fentanyl administered by non-anesthetist. Insertion time and procedural time was recorded. Univariate and multivariate analysis were performed to evaluate the impact of different factors on insertion and procedural time. RESULTS: A total of 238 needles (range, 2-8 per insertion) were implanted, with an average insertion depth of 30 mm (range, 20-40 mm). The mean doses for midazolam and fentanyl were 3 mg (standard deviation [SD] = 1) and 53.3 mcg (SD = 23.9) per insertion, respectively. The median insertion time was 30 minutes (interquartile range [IQR] = 22-40), and the median total procedural time was 4.3 hours (IQR = 3.6-5.2). First time insertion, insertions performed before 2019, and higher midazolam dose were associated with significantly longer insertion time, whereas longer insertion time, MRI-based planning, and insertions performed before 2019 were associated with significantly longer total procedural time. CONCLUSIONS: Outpatient interstitial brachytherapy with non-anesthetist-administered sedation is achievable and well-tolerated. This method may significantly lessen the burden on hospital resources and has the potential to be cost-effective.

Identifying ataxia-telangiectasia in cancer patients: Novel insights from an interesting case and review of literature.

Timely genetic testing leading to early diagnosis of A-T is crucial due to its plethora of implications on clinical management, particularly in those who develop malignancies. Thus, clinicians have to be astute in identifying diagnostic clues of A-T.

Exploring MRI based radiomics analysis of intratumoral spatial heterogeneity in locally advanced nasopharyngeal carcinoma treated with intensity modulated radiotherapy.

BACKGROUND: We hypothesized that spatial heterogeneity exists between recurrent and non-recurrent regions within a tumor. The aim of this study was to determine if there is a difference between radiomics features derived from recurrent versus non recurrent regions within the tumor based on pre-treatment MRI. METHODS: A total of 14 T4NxM0 NPC patients with histologically proven "in field" recurrence in the post nasal space following curative intent IMRT were included in this study. Pretreatment MRI were co-registered with MRI at the time of recurrence for the delineation of gross tumor volume at diagnosis(GTV) and at recurrence(GTVr). A total of 7 histogram features and 40 texture features were computed from the recurrent(GTVr) and non-recurrent region(GTV-GTVr). Paired t-tests and Wilcoxon signed-rank tests were carried out on the 47 quantified radiomics features. RESULTS: A total of 7 features were significantly different between recurrent and non-recurrent regions. Other than the variance from intensity-based histogram, the remaining six significant features were either from the gray-level size zone matrix (GLSZM) or the neighbourhood gray-tone difference matrix (NGTDM). CONCLUSIONS: The radiomic features extracted from pre-treatment MRI can potentially reflect the difference between recurrent and non-recurrent regions within a tumor and has a potential role in pre-treatment identification of intra-tumoral radio-resistance for selective dose escalation.

Navigating the challenges of the COVID-19 outbreak: Perspectives from the radiation oncology service in Singapore.

In December 2019, pneumonia of unknown cause was reported by China to WHO. The outbreak was found to be caused by a coronavirus which was officially named "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2), and the disease caused by it was named 'COVID-19'. The first case in Singapore was confirmed on 23rd January 2020. With lessons learnt from the SARS epidemic in 2003 and the H1N1 flu pandemic in 2009, Singapore was much better prepared to deal with the virus outbreak. The government has taken swift measures to contain and break the chain of transmission. Healthcare workers face the challenge of keeping patients and staff safe from the disease. There is a higher risk of mortality of COVID-19 in cancer patients and hence unique considerations for a radiation oncology department operating in an infectious disease outbreak. This article is the recommendations and adapted workflow from the two National Cancer Centres in Singapore with the endorsement by the working committee of the Chapter of Radiation Oncology, Academy of Medicine, Singapore. It highlights the challenges that radiation oncology departments in Singapore face and the appropriate recommended responses. This includes interventions, business continuity plans and workflow in managing a COVID-19 positive patient on radiotherapy.

Electronic tumor board presentations as the basis for the development of a head and neck cancer database.

BACKGROUND: Multidisciplinary team meetings or tumor boards (TBs) form a pivotal component of oncology practice. The crux of a TB revolves around making treatment decisions based on succinct head and neck cancer (HNC) patient data presentations, which can be challenging and complex. Apart from meticulous TB presentations, discussions and treatment plan documentation is equally important. The aim of this study was to structure an electronic synoptic TB data presentation to address all these areas. The overarching benefits of systematic TB data collection include facilitating audits and research. METHODS: We utilized a secure web-based tool that was used for common scientific research purposes but customized to store HNC patient data. The data points were tabulated across eight TB pages: (a) TB scheduling, (b) patient biodata, (c) diagnosis details, (d) index presentation, (e) images, (f) management and histopathology, (g) TB presentation, and (h) TB discussion and decisions. Each data point leads to additional fields by branching logic to permit further relevant data entry. This was integrated within the patient electronic medical records allowing for a direct internal trajectory to recall TB data. RESULTS: From October 2015 to October 2018, we recorded over 2000 presentations for 1279 individual patients. This is a quality improvement initiative, and hence, the results are more of a broad analysis of our TB presentation process. The most common cancers were squamous cell (523, 41%), thyroid (207, 16%), and nasopharyngeal (139, 11%) carcinomas. Importantly, this system has formed the basis for a number of clinical and translational research projects and audit outcomes. CONCLUSION: Despite TBs being vital to oncologic practice, little attempt has been made to report TB data management. In this study, we present an efficient system that permits the integration of dual functions: TB data presentation and oncologic data collection for research, recall, and audit purposes.

Association of clinical factors with survival outcomes in laryngeal squamous cell carcinoma (LSCC).

AIM: Treatment strategies in laryngeal squamous cell cancer (LSCC) straddle the need for long term survival and tumor control as well as preservation of laryngeal function as far as possible. We sought to identify prognostic factors affecting LSCC outcomes in our population. METHODS: Clinical characteristics, treatments and survival outcomes of patients with LSCC were analysed. Baseline comorbidity data was collected and age-adjusted Charlson Comorbidity Index (aCCI) was calculated. Outcomes of overall survival (OS), progression-free survival (PFS) and laryngectomy-free survival (LFS) were evaluated. RESULTS: Two hundred and fifteen patients were included, 170 (79%) underwent primary radiation/ chemoradiation and the remainder upfront surgery with adjuvant therapy where indicated. The majority of patients were male, Chinese and current/ex-smokers. Presence of comorbidity was common with median aCCI of 3. Median OS was 5.8 years. On multivariable analyses, high aCCI and advanced nodal status were associated with inferior OS (HR 1.24 per one point increase in aCCI, P<0.001 and HR 3.52; p<0.001 respectively), inferior PFS (HR 1.14; p = 0.007 and HR 3.23; p<0.001 respectively) and poorer LFS (HR 1.19; p = 0.001 and HR 2.95; p<0.001 respectively). Higher tumor (T) stage was associated with inferior OS and LFS (HR 1.61; p = 0.02 and HR 1.91; p = 0.01 respectively). CONCLUSION: In our Asian population, the presence of comorbidities and high nodal status were associated with inferior OS, PFS and LFS whilst high T stage was associated with inferior LFS and OS.

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.

Impact of comorbidity on tolerability and survival following curative intent intensity modulated radiotherapy in older patients with nasopharyngeal cancer.

OBJECTIVE: This study aimed to evaluate the predictive factors for survival and acute toxicities in older patients with NPC treated with curative intent IMRT. MATERIALS AND METHODS: Older patients aged 65 years and above with non-metastatic NPC treated with curative intent IMRT between 2003 and 2013 were retrospectively analysed. Variables examined were gender, age, overall stage, chemotherapy use, Eastern Cooperative Oncology Group (ECOG) performance status and comorbidity. The comorbidity severity was determined by adult comorbidity evaluation (ACE-27). We considered hospitalization or placement of feeding tube during and up to one month post radiotherapy as surrogate endpoint for significant acute toxicities. Other endpoints examined were: OS (overall survival), DFS (disease free survival), DSS (disease specific survival). RESULTS: A total of 185 patients were eligible for analysis. Median age was 70 (65-86 years). Most of the patients presented with Stage III and IVA/B (n = 127, 68.7%), of good performance status of ECOG 0-1 (n = 176, 95.1%) and had low comorbidities with ACE-27 score of 0-1 (n = 141, 76.2%). Chemotherapy was delivered to 84 patients (45.4%). OS, DFS, and DSS were 64.5%, 51.4%, and 72.8% respectively. High comorbidity burden but not chemotherapy had significant impact on OS and DFS in patients with advanced stage. Fifty patients (27%) required tube feeding or hospitalization during the course of RT. Males, chemotherapy use and ECOG score ≥2 were significant predictors of tube feeding or hospitalization during RT. CONCLUSION: Curative IMRT was associated with excellent survival outcomes in older patients with NPC. Comorbidity but not chemotherapy was associated with prognosis in advanced stage. Careful monitoring and intensive support should be instituted in older males with ECOG score ≥2 receiving chemo-radiotherapy.

Induction Chemotherapy plus Concurrent Chemoradiotherapy in Endemic Nasopharyngeal Carcinoma: Individual Patient Data Pooled Analysis of Four Randomized Trials.

Purpose: Because of the uneven geographic distribution and small number of randomized trials available, the value of additional induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma (NPC) remains controversial. This study performed an individual patient data (IPD) pooled analysis to better assess the precise role of IC + CCRT in locoregionally advanced NPC.Experimental Design: Four randomized trials in endemic areas were identified, representing 1,193 patients; updated IPD were obtained. Progression-free survival (PFS) and overall survival (OS) were the primary and secondary endpoints, respectively.Results: Median follow-up was 5.0 years. The HR for PFS was 0.70 [95% confidence interval (CI), 0.56-0.86; P = 0.0009; 9.3% absolute benefit at 5 years] in favor of IC + CCRT versus CCRT alone. IC + CCRT also improved OS (HR = 0.75; 95% CI, 0.57-0.99; P = 0.04) and reduced distant failure (HR = 0.68; 95% CI, 0.51-0.90; P = 0.008). IC + CCRT had a tendency to improve locoregional control compared with CCRT alone (HR = 0.70; 95% CI, 0.48-1.01; P = 0.06). There was no heterogeneity between trials in any analysis. No interactions between patient characteristics and treatment effects on PFS or OS were found. After adding two supplementary trials to provide a more comprehensive overview, the conclusions remained valid and were strengthened. In a supplementary Bayesian network analysis, no statistically significant differences in survival between different IC regimens were detected.Conclusions: This IPD pooled analysis demonstrates the superiority of additional IC over CCRT alone in locoregionally advanced NPC, with the survival benefit mainly associated with improved distant control. Clin Cancer Res; 24(8); 1824-33. ©2018 AACR.

Prognostic Model for Stratification of Radioresistant Nasopharynx Carcinoma to Curative Salvage Radiotherapy.

Purpose To investigate for a prognostic index (PI) to personalize recommendations for salvage intensity-modulated radiotherapy (IMRT) in patients with locally recurrent nasopharyngeal carcinoma (lrNPC). Methods Patients with lrNPC from two academic institutions (Sun Yat-Sen University Cancer Center [SYSUCC-A; n = 251 (training cohort)] and National Cancer Centre Singapore [NCCS; n = 114] and SYSUCC-B [n = 193 (validation cohorts)]) underwent salvage treatment with IMRT from 2001 to 2015. Primary and secondary clinical end points were overall survival (OS) and grade 5 toxicity-free rate (G5-TFR), respectively. Covariate inclusion to the PIs was qualified by a multivariable two-sided P < .05. Discrimination and calibration of the PIs were assessed. Results The primary PI comprised covariates that were adversely associated with OS in the training cohort (gross tumor volumerecurrence hazard ratio [HR], 1.01/mL increase [ P < .001], agerecurrence HR, 1.02/year increase [ P = .008]; repeat IMRT equivalent dose in 2-Gy fractions [EQD2] ≥ 68 Gy HR, 1.42 [ P = .03]; prior radiotherapy-induced grade ≥ 3 toxicities HR, 1.90 [ P = .001]; recurrent tumor [rT]-category 3 to 4 HR, 1.96 [ P = .005]), in ascending order of weight. Discrimination of the PI for OS was comparable between training and both validation cohorts (Harrell's C = 0.71 [SYSUCC-A], 0.72 [NCCS], and 0.69 [SYSUCC-B]); discretization by using a fixed PI score cutoff of 252 determined from the training data set yielded low- and high-risk subgroups with disparate OS in the validation cohorts (NCCS HR, 3.09 [95% CI, 1.95 to 4.89]; SYSUCC-B HR, 3.80 [95% CI, 2.55 to 5.66]). Our five-factor PI predicted OS and G5-TFR (predicted v observed 36-month OS and G5-TFR, 22% v 15% and 38% v 44% for high-risk NCCS and 26% v 31% and 45% v 46% for high-risk SYSUCC-B). Conclusion We present a validated PI for robust clinical stratification of radioresistant NPC. Low-risk patients represent ideal candidates for curative repeat IMRT, whereas novel clinical trials are needed in the unfavorable high-risk subgroup.

Thyroid V40 Predicts Primary Hypothyroidism After Intensity Modulated Radiation Therapy for Nasopharyngeal Carcinoma.

PURPOSE: To investigate the various clinical and thyroid dosimetric parameters that could predict the risk of primary hypothyroidism (HT) after intensity modulated radiation therapy (IMRT) for nasopharyngeal carcinoma (NPC) and to determine useful thyroid dose constraints to guide radiation therapy planning. METHODS AND MATERIALS: From September 2009 to August 2012, 102 clinically euthyroid NPC patients were included in this study. All patients were treated with IMRT and randomized to induction chemotherapy followed by concurrent chemo-IMRT or concurrent chemo-IMRT alone. Thyroid function was evaluated by measuring thyroid-stimulating hormone and free thyroxine at each annual follow-up visit. Various clinical and dosimetric parameters (eg, V40 [percentage of thyroid volume receiving >40 Gy]) were obtained. Univariate and multivariate logistic regression analyses were performed to identify predictors of HT. RESULTS: Median follow-up was 48.8 months. Among the 102 patients, 44 (43.1%) developed HT within 2 years after radiation therapy. The median time to HT was 36.7 months (range, 24.9-49.0 months). The 1-year and 2-year cumulative incidence rates of HT were 33% and 44.5%, respectively. Univariate analysis revealed that younger age, early T stage, minimum dose to the thyroid gland, V40, and V45 were associated with HT. On multivariate analysis, younger age (P=.017), early T stage (P=.005), and V40 (P=.009) remained statistically significant. Patients with V40 > 85% had significantly higher cumulative incidence rates of HT than patients with V40 ≤ 85% (P=.007). CONCLUSIONS: Thyroid V40 is predictive of primary HT after IMRT for NPC, and V40 ≤ 85% can be a useful dose constraint to adopt during IMRT planning without compromising tumor coverage.

Comparison between 4-MV and 6-MV radiotherapy in T1N0 glottic cancer.

OBJECTIVES/HYPOTHESIS: The purpose of this study was to report the outcomes of a retrospective consecutive cohort study of patients with T1N0M0 glottic carcinoma treated with 4-MV or 6-MV radiotherapy. STUDY DESIGN: Retrospective case-control study. METHODS: This was a retrospective review of all patients with T1N0M0 glottic carcinoma treated with radiotherapy between January 2000 and December 2012 in the Department of Radiation Oncology at National Cancer Center Singapore. A total of 124 patients were included. Clinical endpoints of interest were: local control (LC), overall survival (OS), and disease-specific survival (DSS). Other prognostic factors for LC were also analyzed: age, gender, smoking status, T substage, dose fraction, field size, anterior commissure involvement, total dose, and overall treatment time. RESULTS: Six-megavolt photon radiotherapy was used in 73 patients and 4-MV photon radiotherapy in 51 patients. Median follow-up was 4.9 years. The 5-year LC and OS were as follows: 4 MV, 91.6% and 83.4%; 6 MV, 88.8% and 82.8%; and the 5-year LC, OS, and DSS for all patients were 90.4%, 83.3%, and 98.3%. There was no significant difference in LR and OS between 4-MV and 6-MV radiotherapy (P = .92, P = .16, respectively). In the univariate analysis of LC, none of the prognostic factors was statistically significant. Twenty patients (23%) developed second primary cancers, the majority in the lungs. CONCLUSIONS: Six-megavolt photon radiotherapy yields comparable results to 4-MV photons. Bolus and computed tomographic simulation are useful to ensure adequate dose coverage of target volume. Follow-up postradiotherapy should incorporate chest imaging, smoking cessation advice, and thyroid function test. LEVEL OF EVIDENCE: 4 Laryngoscope, 127:1061-1067, 2017.

Comparison of Circulating Tumour Cells and Circulating Cell-Free Epstein-Barr Virus DNA in Patients with Nasopharyngeal Carcinoma Undergoing Radiotherapy.

Quantification of Epstein-Barr virus (EBV) cell-free DNA (cfDNA) is commonly used in clinical settings as a circulating biomarker in nasopharyngeal carcinoma (NPC), but there has been no comparison with circulating tumour cells (CTCs). Our study aims to compare the performance of CTC enumeration against EBV cfDNA quantitation through digital PCR (dPCR) and quantitative PCR. 74 plasma samples from 46 NPC patients at baseline and one month after radiotherapy with or without concurrent chemotherapy were analysed. CTCs were captured by microsieve technology and enumerated, while three different methods of EBV cfDNA quantification were applied, including an in-house qPCR assay for BamHI-W fragment, a CE-IVD qPCR assay (Sentosa ®) and a dPCR (Clarity™) assay for Epstein-Barr nuclear antigen 1 (EBNA1). EBV cfDNA quantitation by all workflows showed stronger correlation with clinical stage, radiological response and overall survival in comparison with CTC enumeration. The highest detection rate of EBV cfDNA in pre-treatment samples was seen with the BamHI-W qPCR assay (89%), followed by EBNA1-dPCR (85%) and EBNA1-qPCR (67%) assays. Overall, we show that EBV cfDNA outperforms CTC enumeration in correlation with clinical outcomes of NPC patients undergoing treatment. Techniques such as dPCR and target selection of BamHI-W may improve sensitivity for EBV cfDNA detection.