End Of Intensity-modulated Radiotherapy Research Articles

MRI-based radiomics models predict cystic brain radionecrosis of nasopharyngeal carcinoma after intensity modulated radiotherapy.

To construct radiomics models based on MRI at different time points for the early prediction of cystic brain radionecrosis (CBRN) for nasopharyngeal carcinoma (NPC). A total of 202 injured temporal lobes from 155 NPC patients with radiotherapy-induced temporal lobe injury (RTLI) after intensity modulated radiotherapy (IMRT) were included in the study. All the injured lobes were randomly divided into the training (n = 143) and validation (n = 59) sets. Radiomics models were constructed by using features extracted from T2WI at two different time points: at the end of IMRT (post-IMRT) and the first-detected RTLI (first-RTLI). A delta-radiomics feature was defined as the percentage change in a radiomics feature from post-IMRT to first-RTLI. The radiomics nomogram was constructed by combining clinical risk factors and radiomics signatures using multivariate logistic regression analysis. Predictive performance was evaluated using area under the curve (AUC) from receiver operating characteristic analysis and decision curve analysis (DCA). The post-IMRT, first-RTLI, and delta-radiomics models yielded AUC values of 0.84 (95% CI: 0.76-0.92), 0.86 (95% CI: 0.78-0.94), and 0.77 (95% CI: 0.67-0.87), respectively. The nomogram exhibited the highest AUC of 0.91 (95% CI: 0.85-0.97) and sensitivity of 0.82 compared to any single radiomics model. From the DCA, the nomogram model provided more clinical benefit than the radiomics models or clinical model. The radiomics nomogram model combining clinical factors and radiomics signatures based on MRI at different time points after radiotherapy showed excellent prediction potential for CBRN in patients with NPC.

Phase I/IIa study of concomitant radiotherapy with olaparib and temozolomide in unresectable high grade glioma patients: OLA-TMZ-RTE-01.

2046 Background: Although the Stupp protocol (radiotherapy + temozolomide (TMZ)) remains the mainstay of glioblastoma (GBM) first line treatment after extended surgery, the prognosis is still poor. PARP inhibitors, such as olaparib, may improve GBM outcomes by enhancing cytotoxic effects of ionizing radiation and TMZ. The non-dividing nature of normal brain cells allows a dedicated tumor radiosensitization. We implemented a phase I/IIa trial to assess safety and efficacy of olaparib combined with TMZ concomitant with intensity modulated radiotherapy (IMRT) as a first line treatment in unresectable GBM patients (pts). We herein present results of the phase I step. Methods: Based on the Stupp protocol, 2 treatment periods were considered. The radiotherapy period (RT) occurs after surgery: pts received IMRT (60 Gy/30 fractions/6 wks), oral TMZ (75 mg/m²) during IMRT, and olaparib orally given at the same dose until 4 wks after the end of IMRT. For the maintenance period (MT) from 4 wks after IMRT, pts received TMZ (150 mg/m², days (D) 1-5 every 28 days, for 6 cycles) plus olaparib at the MT dose level up to disease progression or unacceptable toxicity. The phase I included 2 sequential dose escalations (DE1, DE2) of olaparib to split both periods for DLT (Dose Limiting Toxicities) assessment. Olaparib dose levels (DL) were: 50 mg Q12H D 1-3 (DL1), 100 mg Q12H D1-3 (DL2) or D1-5 (DL3), 200 mg Q12H D1-3 (DL4) or D1-5 (DL5) or 200 mg Q12H continuously (DL6). Pts in DE1 received olaparib only during RT to determine the MTD1 (Maximum-Tolerated Dose), by assessing DLT on this period. Next, after olaparib administered at MTD1 during RT, pts in DE2 received olaparib during MT to determine MTD2 (≤MTD1) during the MT period, assessing DLT from the first 2 cycles. DE1 and DE2 were performed by a TITE-CRM (TIme-To-Event Continual Reassessment Method). Results: From 2017 to 2021, 30 pts were enrolled: 20 (67%) men, median age 59 yrs [range 25-70]. 16 and 11 pts were assessable for determining MTD1 and MTD2, respectively. In DE1, 2 pts received olaparib at DL1, 6 at DL2, 6 at DL3, 1 at DL4 and 1 at DL5. 4 pts observed DLT (3 at DL3, 1 at DL5): thrombocytopenia G3-4 (n=4) + neutropenia G4 (n=2). MTD1 was defined as DL2 with estimated probability of DLT of 22.1% [95%CI 8-40.5]. In DE2, 2 pts were treated at DL1, 9 at DL2. 1 pt observed DLT at DL2: thrombocytopenia G4. MTD2 was defined as DL2 with estimated probability of DLT of 13.3% [0.2-0.35]. No interruption of IMRT for toxicity was observed. Excepted DLT, permanent olaparib discontinuation for toxicity was observed in 1 pt during RT and 2 pts during MT. Toxicity induced temporary TMZ interruption in 4 pts, none with permanent discontinuation. No toxic death was observed. Conclusions: Olaparib 100 mg Q12H D1-3 in concomitant with the Stupp protocol has an acceptable safety profile in unresectable GBM pts: it warrants efficacy determination, in the ongoing phase IIa step. Clinical trial information: NCT03212742 .

Tumor Outcomes for ROMAN: Phase 3 Trial of Avasopasem Manganese (GC4419) for Severe Oral Mucositis (SOM) in Patients Receiving Chemoradiotherapy (CRT) for Locally Advanced Head and Neck Cancer (LAHNC)

<h3>Purpose/Objective(s)</h3> Intensity-modulated radiotherapy (IMRT) plus cisplatin is an established treatment for LAHNC, but ∼70% of patients develop SOM (WHO grade [gr] 3 or 4), limiting their ability to eat solids (gr 3) or liquids (gr 4), and often requiring feeding tube nutrition. There are no US-approved drugs to reduce SOM in LAHNC. A radiotherapy (RT)-induced burst of superoxide initiates oral mucositis (OM) development (Sonis 2004). Avasopasem (GC4419, AVA) is an investigational selective small molecule dismutase mimetic designed to convert superoxide to hydrogen peroxide, which may protect normal cells from, and potentially sensitize cancer cells to, RT (Riley DP 2006, El-Mahdy 2020). In a randomized, double-blind phase 2b trial, AVA reduced duration and incidence of SOM due to CRT for LAHNC vs placebo (PBO) (Anderson 2019) and maintained 2-yr tumor outcomes. The present trial (NCT03689712) further assessed safety and efficacy of AVA to reduce SOM due to CRT for LAHNC of the oral cavity (OC) or oropharynx (OP). <h3>Materials/Methods</h3> Double-blind, PBO-controlled trial; patients receiving 60-72 Gy of IMRT (≥50 Gy to ≥2 OM sites) plus cisplatin (weekly or q3 weeks) were randomized 3:2 to IV AVA 90 mg vs PBO M-F before each RT fraction. OM by the WHO scale was assessed by trained evaluators biweekly during RT & weekly for 2 weeks thereafter. Primary endpoint: SOM (WHO gr 3 or 4) incidence through the end of IMRT. Secondary endpoints included SOM duration through 2 weeks post-IMRT, gr 4 OM incidence through the end of IMRT, and tumor outcomes. <h3>Results</h3> N=455 randomized, 407 (241 AVA/166 PBO) primary analysis population; med. age 61; 86% male; 82% OP. Statistically significant 16% relative reduction in SOM incidence (54% vs 64%; <i>p</i>=0.045) and 56% relative reduction in SOM duration (median, 8 vs 18 days; <i>p</i>=0.002) were observed. Gr 4 incidence was reduced 27% (<i>p</i>=0.052). Improvement was seen in multiple secondary and exploratory endpoints (table). Adverse event frequencies were comparable between treatment groups without clear AVA-specific toxicity or increase in cisplatin-attributable toxicity. Available tumor outcome data will be reported. <h3>Conclusion</h3> AVA produced statistically significant, clinically meaningful improvement of SOM vs PBO that was consistent across multiple measures of SOM, with an adverse event profile consistent with expectations for IMRT/cisplatin. Tumor outcomes will be reported. Funder Galera Therapeutics, Inc.

MRI-based radiomics nomogram for predicting temporal lobe injury after radiotherapy in nasopharyngeal carcinoma.

To develop and validate a magnetic resonance imaging (MRI)-based radiomics nomogram model combining radiomic features and clinical factors for the prediction of radiotherapy-induced temporal lobe injury (RTLI) in patients with nasopharyngeal carcinoma (NPC). From 203 NPC cases receiving radiotherapy, 128 RTLI-positive and 278 RTLI-negative lobes were retrospectively analyzed. They were randomly divided into training (n = 285) and validation (n = 121) sets. Three hundred ninety-six texture features based on T2WI images were extracted from each temporal lobe. The minimum redundancy maximum relevance (mRMR) and the least absolute shrinkage and selection operator (LASSO) were used to reduce the dimension of the features and establish a radiomics signature model. Clinical risk factors and the radiomics signature were combined by multivariable logistic regression analysis to construct a radiomics nomogram model. We assessed the performance of the radiomics nomogram on discrimination, calibration, and clinical utility. The radiomics signature consisted of 14 selected features that were significantly associated with RTLI. In the training set, the radiomics nomogram model demonstrated a better predictive performance (AUC, 0.87; 95% CI, 0.82-0.91) than the radiomics model (AUC, 0.71; 95% CI, 0.65-0.78) and clinical model (AUC, 0.73; 95% CI, 0.67-0.79). These results were confirmed in the validation set. The radiomics nomogram model demonstrated good calibration and was clinically useful by decision curve analysis. The radiomics nomogram model combining radiomics signatures and clinical factors is an effective method for the noninvasive prediction of RTLI in NPC patients after radiotherapy. • The radiomics model based on T2WI images at the end of intensity-modulated radiotherapy can predict radiotherapy-induced temporal lobe injury in patients with NPC. • Dosimetric factors can improve the prediction performance of the radiomics model in predicting radiotherapy-induced temporal lobe injury. • An MRI-based radiomics nomogram combining radiomics signatures and clinical factors had better prediction performance than both radiomics and clinical model for the prediction of radiotherapy-induced temporal lobe injury in patients with NPC.

Intermediate Dose-Volume Parameters, Not Low-Dose Bath, Is Superior to Predict Radiation Pneumonitis for Lung Cancer Treated With Intensity-Modulated Radiotherapy

PurposeAlthough intensity-modulated radiotherapy (IMRT) is now a preferred option for conventionally fractionated RT in lung cancer, the commonly used cutoff values of the dosimetric constraints are still mainly derived from the data using three-dimensional conformal radiotherapy (3D-CRT). We aimed to compare the prediction performance among different dosimetric parameters for acute radiation pneumonitis (RP) in patients with lung cancer received IMRT.MethodsA total of 236 patients treated with IMRT were retrospectively reviewed in two independent groups of lung cancer from January 2014 to August 2018. The primary endpoint was grade 2 or higher acute RP (RP2). Dose metrics were generated from the bilateral lung volume outside GTV (VdoseG) and PTV (VdoseP). The associations of RP2 with clinical variables, dose-volume parameters and mean lung dose (MLD) were analyzed by univariate and multivariate logistic regression. The power of discrimination among each predictor was assessed by employing the bootstrapped area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and the integrated discrimination improvement (IDI).ResultsThirty-four (14.4%) out of 236 patients developed acute RP2 after the end of IMRT. The clinical parameters were identified as less important predictors for RP2 based on univariate and multivariate analysis. In both studied groups, the significance of association was more convincing in V20P, V30P, and MLDP (smaller Ps) than V5G and V5P. The largest bootstrapped AUC was identified for the V30P. We found a trend of better discriminating performance for the V20P and V30P, and MLDP than the V5G and V5P according to the higher values in AUC, IDI, and NRI analysis. To limit RP2 incidence less than 20%, the V30P cutoff was 14.5%.ConclusionsThis study identified the intermediate dose-volume parameters V20P and V30P with better prediction performance for acute RP2 than low-dose metrics V5G and V5P. Among all studied predictors, the V30P had the best discriminating power, and should be considered as a supplement to the traditional dose constraints in lung cancer treated with IMRT.

ROMAN: Reduction in oral mucositis with avasopasem manganese (GC4419)–Phase III trial in patients receiving chemoradiotherapy for locally advanced, nonmetastatic head and neck cancer.

TPS6596 Background: Approximately 70% of patients receiving intensity-modulated radiotherapy (IMRT) plus cisplatin for locally advanced head and neck cancer (HNC) develop SOM, defined as WHO Grade 3 or 4, which limits patients' ability to eat solids (Gr 3) or liquids (Gr 4, requiring enteral nutrition). An RT-induced burst of superoxide initiates oral mucositis (OM) development. GC4419, a superoxide dismutase mimetic, interrupts this process by converting superoxide to H2O2. It showed promising reduction of SOM in a published open-label Phase 1b/2a trial (IJROBP 1 Feb 2018). In a subsequent randomized, double-blind placebo-controlled trial in 223 patients receiving IMRT/cisplatin for HNC (ASCO 2018), 90 mg of GC4419 administered M-F prior to IMRT demonstrated statistically significant reduction in SOM duration (p=0.024, median 1.5 days @ 90 mg vs. 19 days placebo) and meaningful reductions @ 90 mg in SOM incidence (43% vs. 65%) and severity (incidence of Grade 4, 16% vs. 30%). The safety results were acceptable and consistent with the known toxicities of IMRT/cisplatin. Methods: 335 patients at multiple centers in the U.S. and Canada with locally-advanced, nonmetastatic head and neck cancer (oral cavity/oropharyngeal) receiving 70 Gy IMRT (&gt;50 Gy to &gt; 2 oral sites) plus cisplatin (40 mg/m2 qwk x 6-7, or 100 mg/m2 q3wk x 3) are being randomized (double-blinded) 3:2 to 90 mg of GC4419 or placebo, M-F before each RT fraction. Enrollment is stratified by cisplatin schedule and treatment setting (definitive vs. post-op). OM by the WHO scale will be assessed twice weekly during RT &amp; weekly for 2 weeks post RT. The primary efficacy endpoint is incidence of SOM through the end of IMRT. Secondary efficacy endpoints include severity (incidence of Grade 4 OM through the end of IMRT), &amp; days of SOM (days from first to last SOM for all patients, with patients never developing SOM having 0 days of SOM by definition). Days of SOM for the subset developing SOM will be analyzed descriptively. Patients will be followed for one year post IMRT for tumor progression/recurrence and for two years for survival. Clinical trial information: NCT03689712 .

A Nomogram for the Prognosis of Nasopharyngeal Carcinoma with MR Imaging-Detected Tumor Residue at the End of Intensity-Modulated Radiotherapy.

ObjectiveThis study set out to institute an effective nomogram to predict the prognosis of nasopharyngeal carcinoma (NPC) using magnetic resonance imaging (MRI)-detected residual tumor at the end of intensity-modulated radiotherapy (IMRT).BackgroundThis study retrospectively analyzed the prognostic factors of NPC using MRI-detected residual tumor at the end of IMRT, in order to individualize the treatment of patients with poor prognosis as early as possible.MethodsOverall, 162 NPC patients with local or regional residual tumor at the end of IMRT were retrospectively analyzed. Based on multivariate Cox regression analysis using the backward stepwise method, a nomogram was generated to predict the prognosis of these patients. Identification, calibration, clinical applicability and reproducibility were evaluated by C-index, time-dependent AUC, calibration curve and bootstrap verification. According to the best cut-off value of total score of prognoses calculated by X-tile software, all patients were separated into either low-risk or high-risk group.ResultsThe nomogram identified age, chemotherapy, N stage, lymph nodes necrosis are significant predictors of prognosis. The AUC of the prediction model is 0.754, and the consistency index is 0.724 (95% confidence interval is 0.659–0.788). The model has good discrimination ability. Through bootstrapping test, the consistency index, corrected slope was 0.723, 0.861, respectively. The calibration slope of predicting 3-year and 5-year overall survival was 1.006 and 1.071, respectively. The calibration curve showed satisfactory calibration effect and good net benefit. The best cut-off value of total score of prognoses calculated by X-tile software was 149.1. Kaplan–Meier survival curve showed that OS and DMFS in the high-risk group were substantially reduced compared to those in the low-risk group.ConclusionWe constructed and validated a new nomogram to help clinicians understand the prognosis of NPC patients with residue at the end of IMRT. With an estimate of the individual risk, clinicians can start treatment decisions as early as possible for high-risk patients with poor prognosis.

Pericardial effusion after definitive concurrent chemotherapy and intensity modulated radiotherapy for esophageal cancer

BackgroundThe literature regarding pericardial effusion after definitive concurrent chemotherapy and intensity modulated radiotherapy (IMRT) for esophageal cancer was lacking. This study aimed to investigate the risk factors of pericardial effusion in esophageal cancer patients undergoing definitive concurrent chemotherapy and IMRT.MethodsA total of 126 consecutive esophageal cancer patients treated with definitive concurrent chemotherapy and IMRT between 2008 and 2018 were reviewed. The pericardial effusion was determined on computed tomography scan of the chest and graded by the Common Terminology Criteria for Adverse Events, version 4.0. The cumulative incidence of pericardial effusion was estimated by the Kaplan–Meier method and compared between groups by the log-rank test. The risk factors of pericardial effusion were determined with multivariate Cox proportional hazards regression analysis.ResultsThe median follow-up time was 14.0 months. Thirty-seven (29.4%) patients had pericardial effusion after a median interval of 6.6 months since the end of IMRT. The cumulative incidence of pericardial effusion of any grade was higher in patients with mean heart dose > 23.45 Gy (p = 0.00018), heart V30 > 33.55% (p = 0.00015), mean pericardium dose > 20.33 Gy (p = 0.00027), and pericardium V20 > 42.55% (p = 0.00018). Furthermore, eight (6.3%) patients had symptoms related to pericardial effusion and were considered as cases with pericardial effusion ≥ grade 3. The cumulative incidence of pericardial effusion ≥ grade 3 was higher in patients with pericardium V30 > 65.80% (p = 0.00028), V40 > 55.35% (p < 0.0001), and V60 > 24.70% (p = 0.0021). Multivariate analyses showed the above dose-volume parameters predicted the risk of pericardial effusion in esophageal cancer.ConclusionsDose-volume parameters predicting the risk of pericardial effusion were identified in esophageal cancer treated with definitive concurrent chemotherapy and IMRT. They could be applied as constraints of IMRT for esophageal cancer.

The value of plasma EBV DNA in monitoring the therapeutic effect of nasopharyngeal carcinoma

Objective To investigate the clinical value of plasma EBV DNA in monitoring clinical efficacy in the treatment of nasopharyngeal carcinoma (NPC). Methods Clinical data of 799 patients initially diagnosed with NPC treated with radical intensity-modulated radiotherapy (IMRT) in our hospital from 2016 to 2017 were analyzed retrospectively. Prior to treatment, the correlation between plasma EBV DNA, clinical stage and tumor progression was analyzed. The relationship between EBV DNA and tumor progression was analyzed after radiotherapy and during follow-up. Results Before IMRT, the level of EBV DNA was positively correlated with both clinical stage and tumor progression (both P<0.001). At 6 to 8 weeks after IMRT, 19(2.3%) patients positive for plasma EBV DNA obtained the worst prognosis and 14 cases had tumor progression. At 6-8 weeks after IMRT, 9 patients were negative for EBV DNA and 3 cases had tumor progression. The tumor progression rate of patients with undetectable plasma EBV DNA at the end of IMRT was only 8.3%(64/772), and the progression-free survival rate significantly differed among three groups (all P<0.05). The sensitivity, specificity and accuracy rates of persistent positive plasma EBV DNA during follow-up were calculated as 77.6%, 100% and 98.1%, respectively. Conclusions The level of plasma EBV DNA in patients with NPC is correlated with tumor bearing and tumor progression prior to IMRT. At 6-8 weeks after IMRT, patients who are persistently positive for EBV DNA obtain the worst prognosis and should be given with appropriate adjuvant therapy. The correlation between persistent positive plasma EBV DNA during follow up and tumor progression yields a high accuracy rate, indicating that plasma EBV DNA is a reliable biomarker for monitoring the clinical efficacy after radical treatment for NPC patients. Key words: Nasopharyngeal neoplasm/intensity-modulated radiotherapy; EBV; DNA; Monitoring

Roman: Reduction in oral mucositis with avasopasem manganese (GC4419)—Phase 3 trial in patients receiving chemoradiotherapy for locally-advanced, non-metastatic head and neck cancer.

TPS6096 Background: Approximately 70% of patients receiving intensity-modulated radiotherapy (IMRT) plus cisplatin for locally advanced head and neck cancer (HNC) develop SOM, defined as WHO Grade 3 or 4, which limits patients' ability to eat solids (Gr 3) or liquids (Gr 4, requiring enteral nutrition). An RT-induced burst of superoxide initiates oral mucositis (OM) development. GC4419, a superoxide dismutase mimetic, interrupts this process by converting superoxide to H2O2. It showed promising reduction of SOM in a published open-label Phase 1b/2a trial (IJROBP 1 Feb 2018). In a subsequent randomized, double-blind placebo-controlled trial in 223 patients receiving IMRT/cisplatin for HNC (ASCO 2018), 90 mg of GC4419 administered M-F prior to IMRT demonstrated statistically significant reduction in SOM duration (p=0.024, median 1.5 days @ 90 mg vs 19 days placebo) and meaningful reductions @ 90 mg in SOM incidence (43% vs 65%) and severity (incidence of Grade 4, 16% vs 30%). The safety profile was acceptable and consistent with the known toxicities of IMRT/cisplatin. Methods: 335 patients at multiple centers in the U.S. and Canada with locally-advanced, nonmetastatic head and neck cancer (oral cavity/oropharyngeal) receiving 70 Gy IMRT (&gt;50 Gy to &gt; 2 oral sites) plus cisplatin (40 mg/m2 qwk x 6-7, or 100 mg/m2 q3wk x 3) are being randomized (double-blinded) 3:2 to 90 mg of GC4419 or placebo, M-F before each RT fraction. Enrollment is stratified by cisplatin schedule and treatment setting (definitive vs post-op). OM by the WHO scale will be assessed twice weekly during RT &amp; weekly for 2 weeks post RT. The primary efficacy endpoint is incidence of SOM through the end of IMRT. Secondary efficacy endpoints include severity (incidence of Grade 4 OM through the end of IMRT), &amp; days of SOM (days from first to last SOM for all patients, with patients never developing SOM having 0 days of SOM by definition). Days of SOM for the subset developing SOM will be analyzed descriptively. Patients will be followed for one year post IMRT for tumor progression/recurrence and for two years for survival. Supported by Galera Therapeutics, Inc. Clinical trial information: NCT03689712.

Local regression and control of T1-2 nasopharyngeal carcinoma treated with intensity-modulated radiotherapy.

ObjectiveTo observe the local regression and control in T1‐2 nasopharyngeal carcinoma (NPC) patients treated with intensity‐modulated radiotherapy (IMRT) and to analyze the related influencing factors.MethodsBetween January 2006 and June 2014, 247 consecutive T1‐2 NPC patients treated with IMRT were retrospectively analyzed, with 126 (51.0%) N0‐1 disease and 121 (49.0%) N2‐3 disease. Among them, 72.9% received platinum‐based chemotherapy. The prescribed dose to gross tumor volume was 66 Gy/30 fractions.ResultsBy the end of IMRT, the chemoradiotherapy (CRT) group had higher local complete response (CR) rate compared with IMRT alone group (92.2% vs 74.6%, P < 0.001), but no significant difference was discovered in 5‐year local control (LC) rate (95.1% vs 94.9%, P = 0.968). Of the rest 31 patients with residual nasopharyngeal lesions after IMRT, those received boost irradiation (67.7%) also showed no improvement in 5‐year LC rate compared with the observational group (95.0% vs 100.0%, P = 0.307). With a median follow‐up of 63 months, the estimated 5‐year LC rate for the whole group was 95.1% (T1 vs T2: 95.9% vs 94.7%, P = 0.186). Prognostic factors for LC were found neither in univariate nor in multivariate analysis. Advanced N stage was found to be the only adverse prognostic factor for all the other survivals.ConclusionsExcellent LC could be achieved in T1‐2 NPC treated with IMRT. The addition of chemotherapy may offer short‐term response benefit, but no significant LC benefit, so did boost irradiation. Attention should be attached to advanced N stage, the exploration of the recurrence‐related factors, and the necessities of the additional treatment.

Long-term cancer-related fatigue outcomes in patients with locally advanced prostate cancer after intensity-modulated radiotherapy combined with hormonal therapy.

The aim of our study was to investigate the relationship between cancer-related fatigue and clinical parameters, and the effect factors of fatigue for the prostate cancer patients. Long-term follow-up is performed using the Fatigue Symptom Inventory before treatment (A), at the end of intensity-modulated radiotherapy (B), and 3 months (C), 12 months (D), 24 months (E), 36 months (F), and 48 months (G) after the end of intensity-modulated radiotherapy. Three dimensions of fatigue are assessed during follow-up: severity, perceived interference with quality of life, and duration in the past week. In all, 97 patients with locally advanced prostate cancer were enrolled in the study. Median follow-up time was 43.9 months. The fatigue index was significantly higher in the prostate-specific antigen >20 ng/mL, Gleason score >8, the Eastern Cooperative Oncology Group scores, and the higher education. The most severe fatigue occurred at time points B and C. The score for duration of fatigue fluctuated across the time points, with significantly increased scores at time points D, E, and F.In conclusion, we show that cancer-related fatigue is the important symptom which affects the quality of life for the prostate cancer patients. For patients with locally advanced prostate cancer with a high Eastern Cooperative Oncology Group score, a Gleason score of >8 points, prostate-specific antigen levels of >20 ng/mL, and high education, attention should be paid to the interference of fatigue with quality of life, especially general level of activity, ability to concentrate, and mood, after radiotherapy combined with hormonal therapy.

Intensity-modulated radiotherapy for gliomas:dosimetric effects of changes in gross tumor volume on organs at risk and healthy brain tissue.

AimThe aim of this study was to explore the effects of changes in the gross tumor volume (GTV) on dose distribution in organs at risk (OARs) and healthy brain tissue in patients with gliomas.MethodsEleven patients suffering from gliomas with intensity-modulated radiotherapy (IMRT) plans treated with a simultaneous integrated boost technique planned before therapy (initial plans) were prospectively enrolled. At the end of radiotherapy, patients underwent repeat computed tomography and magnetic resonance imaging, and IMRT was replanned. The GTV and dosimetric parameters between the initial and replanned IMRT were compared using the Wilcoxon two-related-sample test, and correlations between the initial GTV and the replanned target volumes were assessed using the bivariate correlation test.ResultsThe volume of the residual tumor did not change significantly (P>0.05), the volume of the surgical cavity decreased significantly (P<0.05), and the GTV and target volumes decreased significantly at the end of IMRT (all P<0.05). The near-maximum dose to OARs and volumes of healthy brain tissue receiving total doses of 10–50 Gy were lower in the replanned IMRT than in the initial IMRT (all P<0.05). The GTV in the initial plan was significantly positively correlated with the changes in the GTV and planning target volume 1 that occurred during IMRT (all P<0.05).ConclusionThe reduction in the GTV in patients with gliomas resulted from shrinkage of the surgical cavity during IMRT, leading to decreased doses to the OARs and healthy brain tissue. Such changes appeared to be most meaningful in patients with large initial GTV values.

A retrospective study of the prognostic value of MRI-derived residual tumors at the end of intensity-modulated radiotherapy in 358 patients with locally-advanced nasopharyngeal carcinoma.

ObjectiveTo retrospectively analyze the prognostic value of magnetic resonance imaging (MRI)-derived residual tumors after intensity-modulated radiation therapy (IMRT) in the patients with locally-advanced nasopharyngeal carcinoma.MethodsA total of 358 patients with locally-advanced nasopharyngeal carcinoma who received IMRT were classified as having residual tumors or no residual tumor based on MRI at the end of radiotherapy. The χ2 test, log-rank test, Cox proportional hazards regression model and Kaplan-Meir survival curves were used to investigate the relationship of clinicopathological features and residual tumors and to assess the prognostic value of residual tumors.ResultsThe 3-year overall survival (OS) rate was 73% in the residual tumor group and 90% in the no residual tumor group (HR 2.15, 95% CI 1.21-3.82,, P = 0.007); 3-year local relapse-free survival (LRFS) was 89% in the residual tumor group and 97% in the no residual tumor group (HR 4.46, 95% CI 1.61-12.38, P = 0.002); 3-year disease free survival (DFS) was 67% in the residual tumor group and 82% in the no residual tumor group (HR 2.21, 95% CI 1.40-3.48, P = 0.001). A high prescribed radiation dose (>73.92 Gy) did not increase the percentage volume of the GTVnx receiving 95% of the prescribed dose (GTVnx V95%) or improve any survival outcome.ConclusionThe presence of a residual tumor after IMRT was a significant negative independent prognostic factor for OS, LRFS and DFS. Although IMRT have improved the distribution of radiotherapy doses into the tumors, residual tumors detected by MRI after IMRT are still associated with poor prognosis in patients with advanced nasopharyngeal carcinoma.

Image-guided intensity-modulated radiotherapy for patients with locally advanced gastric cancer: a clinical feasibility study

The aim of this study was to determine the medical and technical feasibility of intensity-modulated radiotherapy (IMRT) in high-risk nonmetastatic gastric cancer stage II and III after primary gastrectomy and D2 lymphadenectomy. A prospective nonrandomized phase II trial was performed on 25 consecutive patients with gastric cancer with high risk (T3-4, N1-3, G2-3, R0-1). The dose delivered was 45 Gy (1.80 Gy per fraction) in IMRT technique. Concurrent 5-fluorouracil-based chemotherapy at 225 mg/m(2) was administered as a continuous intravenous infusion. Primary endpoints were acute gastrointestinal toxicity (CTC 4.0) and technical feasibility of IMRT in regard to dose planning and radiation delivery. Early acute events were defined as clinical and chemical adverse effects of IMRT and concurrent chemotherapy during treatment. By definition, 90 days after the end of IMRT has been evaluated as acute-phase toxicity. No patient had grade 4 or higher acute adverse events. Clinical grade 3 toxicity occurred in two patients (8%) with diarrhea and in one case (4%) with nausea. Hematological changes with grade 3 occurred in three cases (12%) with hemoglobin decrease, in five cases (25%) as leukopenia, and in one case (4%) with thrombocytopenia. The mean dose for liver was 16 Gy and the percentage volume exceeding 30 Gy (V30) was 21%. Mean dose for right and left kidney was 9 and 13 Gy, respectively, and V20 was 9% and 13%, respectively. Heart received a median dose of 15 Gy and V40 was 17%. The mean dose to the bowel was 11 Gy and V40 was 6%. Spinal cord had at maximum 33 Gy in median. Specifics of dose distribution, including the coverage, for the target region were as follows: minimum was 33 Gy, maximum 48.6 Gy, and mean dose 44.6 Gy. The prescribed dose (45 Gy) covered 99% and 95% of planning target volume (OTV) in 66% and 92% of cases, respectively. Median PTV was 15.77 ml (range, 805-3,604 ml). The data support the practical feasibility of IMRT in adjuvant treatment in high-risk gastric cancer in the postoperative setting as a proof of principle. Acute toxicity has been tolerable.

Percutaneous endoscopic gastrostomy in oropharyngeal cancer patients treated with intensity‐modulated radiotherapy with concurrent chemotherapy

The clinical benefit of routine placement of prophylactic percutaneous endoscopic gastrostomy (pPEG) tubes was assessed in patients with oropharyngeal cancer (OPC) who are undergoing intensity-modulated radiotherapy (IMRT) with concurrent chemotherapy. From 1998 through 2009, 400 consecutive patients with OPC who underwent chemoradiation were included. Of these, 325 had a pPEG and 75 did not (nPEG). Weight and albumin change from baseline to mid-IMRT, end of IMRT, 1 month post-IMRT, and 3 months post-IMRT were evaluated. The treating physicians prospectively recorded acute and late toxicities. Significantly lower absolute weight loss at end of IMRT (6.80 kg vs 8.38 kg, P = .007), 1 month post-IMRT (9.06 kg vs 11.33 kg, P = .006), and 3 months post-IMRT (11.10 kg vs 13.09 kg, P = .044) was noted in the pPEG versus nPEG groups. This benefit in reduction of percent weight loss was consistently significant only among patients with BMI < 25. Significant differences were noted in hospital admission rate (15.1% vs 26.7%, P = .026) and volume of nonchemotherapy hydration (8.9 liters vs 17.2 liters, P = .004). There were no differences in percent albumin change, acute dysphagia, acute mucositis, acute xerostomia, chronic dysphagia, radiation treatment duration, and overall survival. Multivariate analysis noted age >55 years (P < .001), female sex (P < .001), and T3/4 category disease (P < .001) were significantly associated with prolonged PEG use. Although pPEG reduced absolute and percent weight loss and need for hospitalizations in our cohort of patients with OPC undergoing chemoradiation, no differences were noted in radiation treatment duration, toxicity, and overall survival. Prolonged PEG use correlated with age >55 years, female sex, and T3/T4 tumors.

Clinical study of ocular damnification after intensity-modulated radiotherapy in patients with nasopharyngeal carcinoma

Objective To study the effect on normal ocular tissues after intensity-modulated radiotherapy (IMRT) in the patients with nasopharyngeal carcinoma.Methods Nineteen nasopharyngeal carcinoma patients confirmed by pathology were enrolled (38 eyes).All Patients tnderwent visual acuity,slit lamp,fundus,visual evoked potential (VEP) and eleetroretinograms (ERG) examination before IMRT,at the end of IMRT,6 months and 12 months after IMRT.Results ① There was no statistically difference in uncorrected and corrected visual acuity at the various examination time points before and after radiotherapy ( P ＞ 0.05 ).② The average latency of VEP P100 before IMRT,at the end of IMRT,at 6 months after IMRT and 12 months after IMRT was ( 99.684 ± 2.484) μV,( 99.947 ± 2.277 ) μV,( 104.000 ± 3.952 ) μV and ( 101.316 ±2.462) μV respectively.The average latency of VEP P100 was significantly prolonged at 6 months after IMRT compared with the time points of before IMRT,the end of IMRT and 12 months after IMRT ( P ＜ 0.05 ).③ The average latency of ERG b wave before IMRT,at the end of IMRT,at 6 months after IMRT and 12months after IMRT was (44.974 ±3.774) ms,(44.816 ±3.368) ms,(43.184 ±2.837) ms and (44.000 ±3.154) ms respectively. The average amplitude of ERG b wave before IMRT,at the end of IMRT,at 6 months after IMRT and 12 months after IMRT was (421.237 ±27.353) μV,(414.763 ±26.188) μY,(419.026 ±24.876) μV,and (419.974 ± 25.894) μV respectively.No statistically difference was found in average latency and amplitude of ERG b wave at the various examination time points before and after radiotherapy ( P ＞0.(05).④ The average amplitude of Op2 wave before IMRT,at the end of IMRT,at 6 months after IMRT and 12 months after IMRT was (63.184 ± 6.028 ) μV,(48.605 ± 6.872 ) μV,( 50.421 ± 6.769 ) μV and (53.026 ±6.074) μV respectively.At the various time points after IMRT,the average amplitude of Op2 wave was significandy lower than before IMRT (P ＜ 0.05 ).Conclusion IMRT can significantly reduce the incidence of ocular complications.There is a good clinical application value of ERG and VEP for evaluating retina and optical nerve functional changes induced by IMRT. Key words: Radiotherapy, intensity-modulated; Nasopharyngeal neoplasms; Ocular complications

Initial experience using intensity-modulated radiotherapy for recurrent nasopharyngeal carcinoma

PurposeTo report our initial experience on the feasibility, toxicity, and tumor control using intensity-modulated radiotherapy (IMRT) for retreatment of recurrent nasopharyngeal carcinoma (NPC). Methods and materialsA total of 49 patients with locoregional recurrent carcinoma in the nasopharynx were treated with IMRT between January 2001 and February 2002 at the Sun Yat-Sen University Cancer Center, Guangzhou, China. The average time to the nasopharyngeal recurrence was 30.2 months after initial conventional RT. The median isocenter dose to the nasopharynx was 70 Gy (range 60.9–78.0) for the initial conventional RT. All patients were restaged at the time of recurrence according to the 1992 Fuzhou, China staging system on NPC. The number of patients with Stage I, II, III and IV disease was 4, 9, 10, and 26, respectively. T1, T2, T3, and T4 disease was found in 4, 9, 11, and 25 patients, respectively. N0, N1, N2, and N3 disease was found in 46, 2, 0, and 1 patient, respectively. Invasion of the nasal cavity, maxillary sinus, ethmoid sinus, sphenoid sinus, and cavernous sinus and erosion of the base of the skull was found in 8, 1, 3, 8, 15, and 20 patients, respectively. The gross tumor volume (GTV) was contoured according to the International Commission on Radiation Units and Measurements (ICRU) Report 62 guidelines. The critical structures were contoured, and the doses to critical structures were constrained according to ICRU 50 guidelines. The GTV in the nasopharynx and positive lymph nodes in the neck received a prescription dose of 68–70 Gy and 60 Gy, respectively. All patients received full-course IMRT. Three patients who had positive lymph nodes were treated with five to six courses of chemotherapy (cisplatin + 5-fluorouracil) after IMRT. ResultsThe treatment plans showed that the percentage of GTV receiving 95% of the prescribed dose (V95-GTV) was 98.5%, and the dose encompassing 95% of GTV (D95-GTV) was 68.1 Gy in the nasopharynx. The mean dose to the GTV was 71.4 Gy. The average doses of the surrounding critical structures were much lower than the tolerable thresholds. At a median follow-up of 9 months (range 3–13), the locoregional control rate was 100%. Three cases (6.1%) of locoregional residual disease were seen at the completion of IMRT, but had achieved a complete response at follow-up. Three patients developed metastases at a distant site: two in the bone and one in the liver and lung at 13 months follow-up. Acute toxicity (skin, mucosa, and xerostomia) was acceptable according to the Radiation Therapy Oncology Group criteria. Tumor necrosis was seen toward the end of IMRT in 14 patients (28.6%). ConclusionThe improvement in tumor target coverage and significant sparing of adjacent critical structures allow the feasibility of IMRT as a retreatment option for recurrent NPC after initial conventional RT. This is the first large series using IMRT to reirradiate local recurrent NPC after initial RT failed. The treatment-related toxicity profile was acceptable. The initial tumor response/local control was also very encouraging. In contrast to primary NPC, recurrent NPC reirradiated with high-dose IMRT led to the shedding of tumor necrotic tissue toward the end of RT. More patients and longer term follow-up are warranted to evaluate late toxicity and treatment outcome.