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Background Peripheral neutrophil-lymphocyte ratio (NLR), reflecting immune-inflammation status, shows great potential for tumor progression and outcome. Pre-treatment NLR does not fully reflect the immune-inflammatory response to treatment. This study aimed to introduce the NLR trend as a new indicator and to investigate its prognostic value in patients with nasopharyngeal carcinoma receiving radiotherapy. Methods This retrospective study evaluated patients with nasopharyngeal carcinoma treated with radiotherapy. The NLR trend value was calculated from the fitted line gradient via the NLRs before, during (at least once), and after each patient's first radiotherapy. The Kaplan–Meier curve and log-rank test were used to calculate and compare survival outcomes of different pretreatment NLRs and NLR trends for progression-free survival, locoregional recurrence-free survival (LRFS), and overall survival at 3 and 5 years. Multivariate Cox regression analyses were performed to assess the association between the NLR trend plus 3- and 5-year overall survival. Results The study included 528 patients. A lower NLR trend predicted worse progression-free survival, LRFS, plus 3- and 5-year overall survival. Multivariate Cox regression analysis showed that the NLR trend independently predicted 3- and 5-year overall survival. Sub-group analysis showed that the prognosis of patients with a low pretreatment NLR and a high NLR trend were superior to those of other groups. Conclusion The NLR trend independently predicted the prognosis of patients with nasopharyngeal carcinoma receiving radiotherapy. The NLR trend and the pretreatment NLR combination is more precise than pretreatment NLR in predicting prognosis. A high NLR trend may be evidence of a positive immune response to radiotherapy in patients with nasopharyngeal carcinoma.

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

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 (IMRT) or volumetric modulated arc therapy (VMAT). The model was developed using clinical data and dose-volume data of thyroid and pituitary gland based on a standard backwards stepwise multivariable logistic regression analysis, then internally validated using 10-fold cross validation. The final NTCP model consisted of age, pre-treatment thyroid stimulating hormone (TSH) 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 ≤ 45Gy was suggested for treatment plan owing to an RHT incidence of 2% versus 61% in the > 45Gy group.

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.

Background To establish a predictive model for the fibrotic level of neck muscles after radiotherapy by using radiomic features extracted from the magnetic resonance imaging (MRI) before and after radiotherapy and planning computed tomography (CT) in nasopharyngeal carcinoma patients. Methods A total of one hundred and eighty-six patients were finally enrolled in this study. According to the specific standard, all patients were divided into three different fibrosis groups. Regions of interests (ROI), including sternocleidomastoids (SCMs), trapezius (T), levator scapulae (LS), and scalenus muscles (S), were delineated manually and used for features extraction on IBEX. XGBoost, a machine learning algorithm, was used for the establishment of the prediction model. First, the patients were divided into training cohort (80%) and testing cohort (20%) randomly. Then the image features of CT or delta changes calculated from pre- and post-radiotherapy MRI images on each cohort constituted training and testing datasets. Then, based on the training dataset, a well-trained prediction model was produced. We used five-fold cross-validation to validate the predictive models. Afterward, the model performance was assessed on the ‘testing’ set and reported in terms of area under the receiver operating characteristic curve (AUC) under five scenarios: (I) only T1 sequence, (II) only T2 sequence, (III) only T1 post-contrast (T1 + C) sequence, (IV) Combination of all MRI sequences, (V) only CT. Results Most of the patients enrolled are male (73.1%), mean age was 47 years, receiving concurrent chemo-radiotherapy as the primary treatment (90.9%). By the end of the final follow-up, most of the patients were rated as mild fibrosis (60.8%). We found the prediction model based on the CT image features outperform all MRI features with an AUC of 0.69 and accuracy of 0.65. Contrarily, the model based on features from all MRI sequence showed lower AUC less than 0.5 and lower accuracy less than 0.6. Conclusions The prediction model based on CT radiomics features has better performance in the prediction of the grade of post-radiotherapy neck fibrosis. This might help guide radiotherapy treatment planning to achieve a better quality of life.

This study aimed to validate previously reported dosimetric parameters, including thyroid volume, mean dose, and percentage thyroid volume, receiving at least 40, 45 and 50 Gy (V40, V45 and V50), absolute thyroid volume spared (VS) from 45, 50 and 60 Gy (VS45, VS50 and VS60), and clinical factors affecting the development of radiation-induced hypothyroidism (RHT). A post hoc analysis was performed in 178 euthyroid nasopharyngeal cancer (NPC) patients from a Phase III study comparing sequential versus simultaneous-integrated boost intensity-modulated radiation therapy. RHT was determined by increased thyroid-stimulating hormone (TSH) with or without reduced free thyroxin, regardless of symptoms. The median follow-up time was 42.5 months. The 1-, 2- and 3-year freedom from RHT rates were 78.4%, 56.4% and 43.4%, respectively. The median latency period was 21 months. The thyroid gland received a median mean dose of 53.5 Gy. Female gender, smaller thyroid volume, higher pretreatment TSH level (≥1.55 μU/ml) and VS60 < 10 cm3 were significantly associated with RHT in univariate analyses. Only pretreatment TSH ≥ 1.55 μU/ml and VS60 < 10 cm3 were significant predictors in multivariate analysis. Our results suggested that patients with pretreatment TSH ≥ 1.55 μU/ml should be cautious about the risk of RHT. The VS60 ≥ 10 cm3 is recommended for treatment planning.

Background Plasma EBV DNA concentrations at the time of diagnosis (pre-EBV) and post treatment (post-EBV) have significant value for predicting the clinical outcome of nasopharyngeal cancer (NPC) patients. However, the prognostic value of the EBV concentration during radiation therapy (mid-EBV) has not been vigorously studied. Patients and methods This was a post hoc analysis of 105 detectable pre-EBV NPC patients from a phase II/III study comparing sequential (SEQ) versus simultaneous integrated boost (SIB) intensity-modulated radiation therapy (IMRT). Plasma EBV DNA concentrations were measured by PCR before commencement of IMRT, at the 5th week of radiation therapy and 3 months after the completion of IMRT. The objective was to identify the prognostic value of mid-EBV to predict overall survival (OS), progression-free survival (PFS) and distant metastasis-free survival (DMFS). Results A median pre-EBV was 6880 copies/ml. Mid-EBV and post-EBV were detectable in 14.3% and 6.7% of the patients, respectively. The median follow-up time was 45.3 months. The 3-year OS, PFS and DMFS rates were 86.0% vs. 66.7% (p = 0.043), 81.5% vs. 52.5% (p = 0.006), 86.1% vs. 76.6% (p = 0.150), respectively, for those with undetectable mid-EBV vs. persistently detectable mid-EBV. However, in the multivariate analysis, only persistently detectable post-EBV was significantly associated with a worse OS (hazard ratio (HR) = 6.881, 95% confident interval (CI) 1.699-27.867, p = 0.007), PFS (HR = 5.117, 95% CI 1.562–16.768, p = 0.007) and DMFS (HR = 129.071, 95%CI 19.031–875.364, p < 0.001). Conclusions Detectable post-EBV was the most powerful adverse prognostic factor for OS, PFS and DMFS; however, detectable mid-EBV was associated with worse OS, PFS especially Local-PFS (LPFS) and may facilitate adaptive treatment during the radiation treatment period.

This study was performed to compare the acute and late toxicities between sequential (SEQ) and simultaneous integrated boost (SIB) intensity-modulated radiotherapy (IMRT) in nasopharyngeal carcinoma (NPC). Stage I-IVB NPC patients were randomized to receive SEQ-IMRT or SIB-IMRT. SEQ-IMRT consisted of two plans: 2 Gy × 25 fractions to low-risk planning target volume (PTV) followed by a sequential boost (2 Gy × 10 fractions) to high-risk PTV, while SIB-IMRT treated low- and high-risk PTVs with doses of 56 and 70 Gy in 33 fractions. Toxicities and survival outcomes were analyzed. Between October 2010 and September 2015, of the 209 patients who completed treatment, 102 in the SEQ and 107 in the SIB arm were analyzed. The majority had undifferentiated squamous cell carcinoma (82%). Mucositis and dysphagia were the most common grade 3–5 acute toxicities. There were no statistically significant differences in the cumulative incidence of grade 3–4 acute toxicities between the two arms (59.8% in SEQ vs. 58.9% in SIB; P = 0.892). Common grade 3–4 late toxicities for SEQ and SIB included hearing loss (2.9 vs. 8.4%), temporal lobe injury (2.9 vs. 0.9%), cranial nerve injury (0 vs. 2.8%), and xerostomia (2 vs. 0.9%). With the median follow-up of 41 months, 3‑year progression-free and overall survival rates were 72.7 vs. 73.4% (P = 0.488) and 86.3 vs. 83.6% (P = 0.938), respectively. SEQ and SIB provide excellent survival outcomes with few late toxicities. According to our study, SIB with a satisfactory dose–volume constraint to nearby critical organs is the technique of choice for NPC treatment due to its convenience.

PURPOSE/OBJECTIVE(S) 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. This study sets to evaluate the prognostic factors and recovery pattern of cranial neuropathies, using longitudinal clinical data from two tertiary oncology centers in endemic areas. MATERIALS/METHODS Case records of consecutive T4 NPC patients who received definitive IMRT in 2004-2019 were reviewed. Distribution of cranial neuropathies at disease presentation were recorded. Time to partial and full neurological recovery, time from neurological recovery to re-palsy, relapse-free survival (RFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Predictors for neurological recovery 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 2 months (IQR, 1-4 months). All patients completed definitive IMRT, and 94% of patients received chemotherapy. The 5-year RFS and OS of the combined cohort were 50.8% and 60.1% respectively. Median RFS of patients with single versus multiple neuropathies were 5.8 years and 4.2 years (P = 0.62). Cranial nerves (CN) VI (56.4%), V2 (47.9%) and V3 (29.2%) were most frequently involved. Over a median follow-up of 6.4 years, 111 (22%) and 289 (57.3%) neuropathies attained partial and full recovery respectively, and 86% of the recoveries occurred within the first year after definitive radiotherapy. CN III, IV, VI had the highest 5-year full recovery rate (72.7%), followed by CN V1-3 (60.3%), CN XII (48.6%), and CN II (18.2%) (P < 0.001). Positive smoking history, optic nerve involvement, and long 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 at the base of skull. CONCLUSION Rate and durability of cranial neuropathy recovery in this contemporary NPC cohort compared favorably with data from the 2D radiotherapy era. Both patient and disease factors affected the chance of nerve recovery. Re-palsy of recovered nerves should prompt careful evaluation for local recurrence.

Epstein-Barr virus (EBV) DNA has been recognized as a promising tumor marker for nasopharyngeal carcinoma (NPC). This study aims to demonstrate the prevalence of plasma EBV DNA and its temporal correlation with treatment outcomes in the modern era. A total of 204 patients with Stage I–IVB NPC treated with intensity-modulated radiotherapy (IMRT) were enrolled. Quantitative plasma EBV DNA measurement was performed before treatment (pre-IMRT), on the fifth week of radiation (mid-IMRT), at 3 months after radiation (post-IMRT), then every 6 months until disease relapse. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan–Meier method. Plasma EBV DNA was detected in 110 patients (53.9%), with a median pre-IMRT EBV DNA level of 8005 copies/ml. Significant correlation was noted between pre-IMRT EBV DNA level and disease stage, but not between pre-IMRT EBV DNA level and World Health Organization classification. With a median follow-up time of 35.1 months, the 3-year PFS and OS rates were higher in the group with undetectable pre-IMRT EBV DNA level compared with in the group in which it was detectable. When classified according to disease stage and pre-IMRT EBV DNA, patients with early disease and detectable pre-IMRT EBV DNA experienced poorer survival than those with locally advanced disease and undetectable pre-IMRT EBV DNA. According to the dynamic changes in EBV DNA level between pre-IMRT and mid/post IMRT, survival was significantly higher in patients who achieved an undetectable level following treatment. On multivariate analysis, post-IMRT EBV DNA level was the strongest predictor of all treatment outcomes (P

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 (

Toxicities resulting from platinum based chemotherapy in head and neck cancer is a cause for much concern. There is a lack of clinical criteria for defining these patient populations, which has posed serious problems associated with increased morbidity and consequently an adverse effect on patients' quality of life. In addition, there is a lack of consensus on clinical criteria for defining such patient populations, who may be unsuitable for concurrent chemoradiotherapy. A group of experts in the field of head and neck cancer from the Asia Pacific Region convened in August 2014 in Korea to discuss the development of a set of clinical criteria in order to fill the knowledge gap and provide a reference tool for head and neck oncologists. This paper reports the final output from this meeting and the accompanying literature review, with the aim of aiding clinical decision making with the help of some clinical criteria to identify platinum unsuitable patient populations in head and neck cancer management. Some alternative treatment options are also discussed in this paper. (C) 2015 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license.

Background. The aim of the prospective phase II study was to evaluate the efficacy and toxicities of concurrent carboplatin with intensity-modulated radiotherapy (IMRT) in the treatment of nasopharyngeal carcinoma (NPC). Patients and methods. Between October 2005 and November 2011, 73 stage II‒IVB NPC patients received IMRT 70 Gy concurrently with three cycles of carboplatin (AUC 5) every three weeks, followed by three cycles of adjuvant carboplatin (AUC 5) and 5-FU (1,000 mg/m2/day for four days) every four weeks. All patients were evaluated for tumour response using response evaluation criteria in solid tumour (RECIST) criteria, survival analysis using Kaplan-Meier methods, and toxicities according to common terminology criteria for adverse events (CTCAE) version 4.0. Results. At three months after chemoradiation, 82.2% and 17.8% of patients achieved complete and partial response, respectively. With a median follow-up of 48.1 months (1.3‒97.8 months), 9.6% and 17.8% had local recurrence and distant metastasis, respectively. The median survival was not reached. A three-year overall survival was 83.6% and a progression-free survival was 65.3%. Regarding treatment compliance, 97.2%, 68.5% and 69.8% completed radiation treatment, concurrent carboplatin and adjuvant chemotherapy, respectively. Grade 3‒4 acute toxicities were oral mucositis (16.4%), dysphagia (16.4%), xerostomia (15.1%) and haematotoxicity (6.8%). Conclusions. Carboplatin concurrently with IMRT provided excellent tumour response, manageable toxicities and good compliance. This should be considered as an alternative treatment for NPC patients.

Purpose: A unique capability of the CyberKnife system is dynamic target tracking. However, not all patients are eligible for this approach. Rather, their tumors are tracked statically using the vertebral column for alignment. When using static tracking, the internal target volume (ITV) is delineated on the four-dimensional (4D) CT scan and an additional margin is added to account for setup uncertainty [planning target volume (PTV)]. Treatment margins are difficult to estimate due to unpredictable variations in tumor motion and respiratory pattern during the course of treatment. The inability to track the target and detect changes in respiratory characteristics might result in geographic misses and local tumor recurrences. The purpose of this study is to develop a method to evaluate the adequacy of ITV-to-PTV margins for patients treated in this manner. Methods: Data from 24 patients with lesions in the upper lobe (n = 12), middle lobe (n = 3), and lower lobe (n = 9) were included in this study. Each patient was treated with dynamic tracking and underwent 4DCT scanning at the time of simulation. Data including the 3D coordinates of the target over the course of treatment were extracted from the treatment log files and used to determine actual target motion in the superior–inferior (S–I), anterior–posterior (A–P), and left–right (L–R) directions. Different approaches were used to calculate anisotropic and isotropic margins, assuming that the tumor moves as a rigid body. Anisotropic margins were calculated by separating target motion in the three anatomical directions, and a uniform margin was calculated by shifting the gross tumor volume contours in the 3D space and by computing the percentage of overlap with the PTV. The analysis was validated by means of a theoretical formulation. Results: The three methods provided consistent results. A uniform margin of 4.5 mm around the ITV was necessary to assure 95% target coverage for 95% of the fractions included in the analysis. In the case of anisotropic margins, the expansion required in the S–I direction was larger (8.1 mm) than those in the L–R (4.9 mm) and A–P (4.5 mm) directions. This margin accounts for variations of target position within the same treatment fraction. Conclusions: The use of bony alignment for CyberKnife lung stereotactic body radiation therapy requires careful considerations, in terms of the potential for increased toxicity or local miss. Our method could be used by other centers to determine the adequacy of ITV-to-PTV margins for their patients.

Stereotactic body radiation therapy (SBRT) to central lung tumors is associated with normal -tissue toxicity. Highly conformal technologies may reduce the risk of complications. This study compares physical dose characteristics and anticipated risks of radiation pneumonitis (RP) among three SBRT modalities: robotic radiosurgery (RR), helical tomotherapy (HT) and volumetric modulated arc therapy (VMAT). Nine patients with central lung tumors ≤5 cm were compared. RR, HT and VMAT plans were developed per RTOG 0831. Dosimetric comparisons included target coverage, conformity index, heterogeneity index, gradient index, maximal dose at 2 cm from target (D2 cm), and dose-volume parameters for organs at risk (OARs). Efficiency endpoints included total beam-on time and monitor units. RP risk was derived from Lyman-Kutcher-Burman modeling on in-house software. The average GTV and PTV were 11.6 ± 7.86 cm3 and 36.8 ± 18.1 cm3. All techniques resulted in similar target coverage (p = 0.64) and dose conformity (p = 0.88). While RR had sharper fall-off gradient (p = 0.002) and lower D2 cm (p = 0.02), HT and VMAT produced greater homogeneity ( p < 0.001) and delivery efficiency (p = 0.001). RP risk predicted from whole or contralateral lung volumes was less than 10%, but was 2-3 times higher using ipsilateral volumes. Using whole (p = 0.04, p = 0.02) or ipsilateral (p = 0.004, p = 0.0008) volumes, RR and VMAT had a lower risk of RP than HT. Using contralateral volumes, RR had the lowest RP risk (p = 0.0002, p = 0.0003 versus HT, VMAT). RR, HT and VMAT were able to provide clinically acceptable plans following the guidelines provided by RTOG 0813. All techniques provided similar coverage and conformity. RR seemed to produce a lower RP risk for a scenario of small PTV-OAR overlap and small PTV. VMAT and HT produced greater homogeneity, potentially desirable for a large PTV-OAR overlap. VMAT probably yields the lowest RP risk for a large PTV. Understanding subtle differences among these technologies may assist in situations where multiple choices of modality are available.

Objective Plasma Epstein-Barr virus (EBV) DNA concentration at the time of diagnosis (pre-EBV) can be used to stratify risk for nasopharyngeal cancer (NPC) patients. However, pre-EBV cut-off values vary among studies. Methods This was a post hoc analysis of 208 NPC patients from a phase II/III study comparing sequential (SEQ) vs. simultaneous integrated boost (SIB) intensity modulated radiation therapy. The objective was to identify the optimal pre-EBV cut-off value to predict overall survival (OS), progression free survival (PFS) and distant metastatic free survival (DMFS) rates. Results The pre-EBV and post-treatment EBV DNA (post-EBV) were detectable in 59.1% and 3.8% of the patients, respectively. A new pre-EBV cut-off value of 2300 copies/ml was identified by the receiver operating characteristics analysis. This cut-off value showed 82% sensitivity, 59% specificity and 31.7% positive and 93.5% negative predictive values in predicting OS. The 3-year OS, PFS and DMFS were 95.6 vs. 73.8%, 89.8 vs. 55.3% and 93 vs. 70.1% for pre-EBV < vs. ≥2300 copies/ml, respectively. Older age group (≥45 years), high pre-EBV and detectable post-EBV concentration were independent predictors for OS, PFS and DMFS in a multivariate analysis. When the stage grouping and pre-EBV value were combined, a subgroup of patients with stage II-III and pre-EBV values

The purpose of the study is to compare the efficacy of benzydamine HCl with sodium bicarbonate in the prevention of concurrent chemoradiation-induced oral mucositis in head and neck cancer patients. Sixty locally advanced head and neck cancer patients treated with high-dose radiotherapy concurrently with platinum-based chemotherapy were randomly assigned to receive either benzydamine HCl or sodium bicarbonate from the first day of treatment to 2 weeks after the completion of treatment. The total score for mucositis, based on the Oral Mucositis Assessment Scale (OMAS), was used for the assessment, conducted weekly during the treatment period and at the fourth week of the follow-up. Pain score, all prescribed medications, and tube feeding needs were also recorded and compared. The median of total OMAS score was statistically significant lower in patients who received benzydamine HCl during concurrent chemo-radiotherapy (CCRT) than in those who received sodium bicarbonate, (p value

A unique capability of the CyberKnife system is dynamic target tracking. However, not all patients are eligible for this approach. Rather, their tumors are tracked statically using the vertebral column for alignment. When using static tracking, the internal target volume (ITV) is delineated on the four-dimensional (4D) CT scan and an additional margin is added to account for setup uncertainty [planning target volume (PTV)]. Treatment margins are difficult to estimate due to unpredictable variations in tumor motion and respiratory pattern during the course of treatment. The inability to track the target and detect changes in respiratory characteristics might result in geographic misses and local tumor recurrences. The purpose of this study is to develop a method to evaluate the adequacy of ITV-to-PTV margins for patients treated in this manner.Data from 24 patients with lesions in the upper lobe (n = 12), middle lobe (n = 3), and lower lobe (n = 9) were included in this study. Each patient was treated with dynamic tracking and underwent 4DCT scanning at the time of simulation. Data including the 3D coordinates of the target over the course of treatment were extracted from the treatment log files and used to determine actual target motion in the superior-inferior (S-I), anterior-posterior (A-P), and left-right (L-R) directions. Different approaches were used to calculate anisotropic and isotropic margins, assuming that the tumor moves as a rigid body. Anisotropic margins were calculated by separating target motion in the three anatomical directions, and a uniform margin was calculated by shifting the gross tumor volume contours in the 3D space and by computing the percentage of overlap with the PTV. The analysis was validated by means of a theoretical formulation.The three methods provided consistent results. A uniform margin of 4.5 mm around the ITV was necessary to assure 95% target coverage for 95% of the fractions included in the analysis. In the case of anisotropic margins, the expansion required in the S-I direction was larger (8.1 mm) than those in the L-R (4.9 mm) and A-P (4.5 mm) directions. This margin accounts for variations of target position within the same treatment fraction.The use of bony alignment for CyberKnife lung stereotactic body radiation therapy requires careful considerations, in terms of the potential for increased toxicity or local miss. Our method could be used by other centers to determine the adequacy of ITV-to-PTV margins for their patients.

Background To investigate acute and late toxicities comparing sequential (SEQ-IMRT) versus simultaneous integrated boost intensity modulated radiotherapy (SIB-IMRT) in nasopharyngeal carcinoma (NPC) patients. Methods Newly diagnosed stage I-IVB NPC patients were randomized to receive SEQ-IMRT or SIB-IMRT, with or without chemotherapy. SEQ-IMRT consisted of two sequential radiation treatment plans: 2Gy x 25 fractions to low-risk planning target volume (PTV-LR) followed by 2Gy x 10 fractions to high-risk planning target volume (PTV-HR). In contrast, SIB-IMRT consisted of only one treatment plan: 2.12Gy and 1.7Gy x 33 fractions to PTV-HR and PTV-LR, respectively. Toxicities were evaluated according to CTCAE version 4.0. Results Between October 2010 and November 2013, 122 eligible patients were randomized between SEQ-IMRT (54 patients) and SIB-IMRT (68 patients). With median follow-up time of 16.8 months, there was no significant difference in toxicities between the two IMRT techniques. During chemoradiation, the most common grade 3–5 acute toxicities were mucositis (15.4 % vs 13.6 %, SEQ vs SIB, p = 0.788) followed by dysphagia (9.6 % vs 9.1 %, p = 1.000) and xerostomia (9.6 % vs 7.6 %, p = 0.748). During the adjuvant chemotherapy period, 25.6 % and 32.7 % experienced grade 3 weight loss in SEQ-IMRT and SIB-IMRT (p = 0.459). One-year overall survival (OS) and progression-free survival (PFS) were 95.8 % and 95.5 % in SEQ-IMRT and 98 % and 90.2 % in SIB-IMRT, respectively (p = 0.472 for OS and 0.069 for PFS). Conclusion This randomized, phase II/III trial comparing SIB-IMRT versus SEQ-IMRT in NPC showed no statistically significant difference between both IMRT techniques in terms of acute adverse events. Short-term tumor control and survival outcome were promising.