Radical Intensity-modulated Radiotherapy Research Articles

Prognostic Value of Tumor Volume Reduction during Radiotherapy in Patients with Locally Advanced Cervical Cancer in Different Risk Groups

To evaluate the risk factors of patients with locally advanced cervical cancer (LACC) undergoing radical radiotherapy (with or without concurrent chemotherapy) and to assess the prognostic value of tumor volume regression (TVR) based on magnetic resonance imaging (MRI) in different risk groups. A retrospective analysis was performed on 176 individuals diagnosed with stage IIA-IVA cervical cancer (CC) who underwent radical intensity-modulated radiotherapy in our center between January 2012 and December 2020. The tumor volume before radiotherapy (TVp) and before brachytherapy (TVmid) were evaluated based on three-dimensional MRI images, TVR = (TVp -TVmid)/TVp × 100%. Kaplan-Meier curves were used to assess patient's overall survival (OS) and progression-free survival (PFS). Prognostic factors were identified using Cox proportional hazards models. For the entire cohort, patients with TVR ≥ 94% had better 5-year OS (82.7% vs 49.8%, p<0.001) and 5-year PFS (82.5% vs 51.1%, p<0.001) compared to TVR < 94%. Patients with TVR ≥ 94% were more likely to receive concurrent chemoradiotherapy (CCRT) than those with TVR < 94% (70.1% vs 40.5%, p<0.05). Among patients undergoing CCRT, those with a TVR ≥ 94% had a better prognosis than those with a TVR < 94%. However, among patients who received RT alone, those with TVR ≥ 94% had better PFS but no statistically significant difference in OS. Likewise, among patients with CYFRA21-1 < 7.7 ng/ml, patients with TVR ≥ 94% had a better prognosis. However, TVR was not a prognostic factor in patients with CYFRA21-1 ≥ 7.7 ng/ml. Both CYFRA21-1 (OS, PFS interaction, p<0.001) and FIGO stage (PFS interaction, p = 0.035) were found to significantly impact predictive effects of TVR. In LACC patients with CRYFA21-1 < 7.7 ng/ml who received CCRT, TVR was an important prognostic factor. However, in patients with CRYFA21-1 ≥ 7.7 ng/ml who received RT alone, the prognostic value of TVR needs to be further explored.

Reducing Target Volumes of Intensity Modulated Radiation Therapy After Induction Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma: Long-Term Results of a Prospective, Multicenter, Randomized Trial

The objective of this study was to estimate the long-term survival, late toxicity profile, and quality of life of patients with locoregionally advanced nasopharyngeal carcinoma (NPC) treated with combined induction chemotherapy (IC) and concurrent chemoradiotherapy from a clinical trial focused on reducing the target volume of intensity modulated radiation therapy (IMRT). This prospective, randomized clinical trial was conducted across 6 Chinese hospitals and included 212 patients with stage III-IVB NPC who were randomly allocated to a pre-IC or post-IC group. Eligible patients were treated with 2 cycles of IC+CCRT. All patients underwent radical IMRT. Gross tumor volumes of the nasopharynx were delineated according to pre-IC and post-IC tumor extent in the pre-IC and post-IC groups, respectively. After a median follow-up of 98.4 months, 32 of 97 (32.9%) and 33 of 115 (28.7%) patients experienced treatment failure or died in the pre-IC and post-IC groups, respectively. None of the patients developed grade 4 late toxicity. Late radiation-induced toxicity predominantly manifested as grade 1 to 2 subcutaneous fibrosis, hearing loss, tinnitus, and xerostomia, whereas grade 3 late toxicity included xerostomia and hearing loss. The 5-year estimated overall, progression-free, locoregional recurrence-free, and distant metastasis-free survival rates in the pre-IC and post-IC groups were 78.2% versus 83.3%, 72.0% versus 78.1%, 90.2% versus 93.5%, and 78.1% versus 82.1%, respectively. The pre-IC group had a significantly higher incidence of xerostomia and hearing damage than the post-IC group. In terms of quality of life, compared with the pre-IC group, the post-IC group showed significant improvement in cognitive function (P=.045) and symptoms including dry mouth (P=.004), sticky saliva (P=.047), and feeling ill (P=.041). After long-term follow-up, we confirmed that reducing the target volumes of IMRT after IC in locoregionally advanced NPC showed no inferiority in terms of the risk of locoregional relapse and potentially improved quality of life and alleviated late toxicity.

Efficacy of concurrent chemoradiotherapy alone for loco-regionally advanced nasopharyngeal carcinoma: long-term follow-up analysis

BackgroundTo analysis the clinical outcomes of concurrent chemoradiotherapy (CCRT) alone based on 10-year results for loco-regionally advanced nasopharyngeal carcinoma (LANPC), so as to provide evidence for individualized treatment strategy and designing appropriate clinical trial for different risk LANPC patients.MethodsConsecutive patients with stage III-IVa (AJCC/UICC 8th) were enrolled in this study. All patients received radical intensity-modulated radiotherapy (IMRT) and concurrent cisplatin chemotherapy (CDDP). The hazard ratios (HRs) of death risk in patients with T3N0 was used as baseline, relative HRs were calculated by a Cox proportional hazard model to classify different death risk patients. Survival curves for the time-to-event endpoints were analyzed by the Kaplan–Meier method and compared using the log-rank test. All statistical tests were conducted at a two-sided level of significance of 0.05.ResultsA total of 456 eligible patients were included. With 12-year median follow-up, 10-year overall survival (OS) was 76%. 10-year loco-regionally failure-free survival (LR-FFS), distant failure-free survival (D-FFS) and failure-free survival (FFS) were 72%, 73% and 70%, respectively. Based on the relative hazard ratios (HRs) of death risk, LANPC patients were classified into 3 subgroups, low-risk group (T1-2N2 and T3N0-1) contained 244 patients with HR < 2; medium-risk group (T3N2 and T4N0-1) contained 140 patients with HR of 2 – 5; high-risk group (T4N2 and T1-4N3) contained 72 patients with HR > 5. The 10-year OS for patients in low-, medium-, and high-risk group were 86%, 71% and 52%, respectively. Significantly differences of OS rates were found between each of the two groups (low-risk group vs. medium-risk group, P < 0.001; low-risk group vs. high-risk group, P < 0.001; and medium-risk group vs. high-risk group, P = 0.002, respectively). Grade 3–4 late toxicities included deafness/otitis (9%), xerostomia (4%), temporal lobe injury (5%), cranial neuropathy (4%), peripheral neuropathy (2%), soft tissue damage (2%) and trismus (1%).ConclusionsOur classification criteria demonstrated that significant heterogeneity in death risk among TN substages for LANPC patients. IMRT plus CDDP alone maybe suitable for low-risk LANPC (T1-2N2 or T3N0-1), but not for medium- and high-risk patients. These prognostic groupings provide a practicable anatomic foundation to guide individualized treatment and select optimal targeting in the future clinical trials.

Impaired geriatric 8 score is associated with worse survival after radical intensity modulated radiation therapy in elderly patients with nasopharyngeal carcinoma

Background Geriatric 8 score (G8) was an independent prognostic factor for survival and toxicities in various malignancies, but it has never been tested in nasopharyngeal carcinoma (NPC). Objectives To evaluate the value of G8 in predicting survival in elderly patients with NPC. Material and Methods Patients with NPC aged ≥70 who received intensity-modulated radiation therapy were recruited into this study. The overall survival (OS), progression-free survival (PFS), locoregional recurrence rate (LRR), and distant metastasis rate (DMR) between the patients with G8 > 14 and G8 ≤ 14 were calculated using the Kaplan-Meier method and compared with the Log-rank test. Cox proportional hazards model was applied to perform univariate and multivariate analysis. Results G8 ≤ 14 had significantly reduced OS (p = .001) and PFS (p = .032) than those with G8 > 14 by log-rank test. G8 score remained an independent prognosticator for OS (HR = 0.490, 95% CI = 0.267–0.900, p = .021) and was a borderline significance towards PFS (HR = 0.639, 95% CI = 0.386–1.058, p = .082) in multivariate analysis. Grade 3–4 acute toxicities were significantly more common in patients with G8 ≤ 14 than in those with G8 > 14. Conclusions and significance G8 is useful in predicting the OS in elderly patients with NPC. Further prospective study stratified by G8 is needed to explore the value of CT in elderly patients with NPC.

Failure pattern and suggestions for target volume delineation of carcinoma showing thymus-like differentiation treated with intensity-modulated radiotherapy

BackgroundTo review our long-term clinical experience, analyze the failure patterns, and give suggestions for target volume delineation of carcinoma showing thymus-like differentiation (CASTLE) treated with intensity-modulated radiotherapy (IMRT).MethodsFrom April 2008 to May 2019, 30 patients with CASTLE treated by postoperative or radical IMRT in our center were retrospectively reviewed. A total dose of 56-60 Gy in 28–30 fractions was prescribed to patients without residual disease and 66 Gy in 33 fractions for patients with residual or unresectable disease. Survival rates were calculated using the Kaplan-Meier method. Treatment-related toxicities were graded by National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.0.ResultsAmong the 30 patients, 12 (40%) received partial resection or biopsy. Lateral lymph node metastasis was observed in 7 (23.3%) patients. During follow-up, regional lymph node recurrence occurred in 2 patients and distant metastasis in 5 patients. With a median follow-up time of 63.5 months, the 5-year local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), overall survival (OS) and progression-free survival (PFS) rates were 100, 88.9, 78.9, 93.1 and 78.9%, respectively. For patients with no lateral neck node metastasis, prophylactic radiotherapy for lateral neck nodal regions failed to improve RRFS (p = 0.381) and OS (p = 0.153).ConclusionDistant metastasis was the major failure pattern for CASTLE after surgery and IMRT. For patients with no lateral neck node metastasis, the omission of irradiation for lateral neck nodal regions seems to be safe and feasible.

Body Composition as a Predictor of the Survival in Anal Cancer.

Simple SummaryObesity and overweight are major health hazards in general and for cancer patients in specific. In this study, we used two parameters for measuring obesity, namely body mass index (BMI) and visceral-to-subcutaneous fat ratio (VSR), to evaluate the effect of obesity on the survival of patients with cancer of the anus. Our results show that obese patients live shortly compared to patients without obesity. Measures to counter obesity at the time of diagnosis could be necessary to improve the outcomes of treatment.Background and aim: Sarcopenia and body composition parameters such as visceral and subcutaneous adipose tissue and visceral-to-subcutaneous adipose tissue ratio have been shown to be relevant biomarkers for prognosis in patients with different types of cancer. However, these findings have not been well studied in anal cancer to date. Therefore, the aim of this study was to evaluate the prognostic value of different body composition parameters in patients undergoing radiation therapy for the treatment of anal cancer with curative intent. Material and Methods: After approval by the institutional ethical committee, we retrospectively identified 81 patients in our local registry, who received radical intensity-modulated radiotherapy for the management of anal squamous cell cancer (ASCC). Clinical information, including body mass index (BMI), survival, and toxicities outcome, were retrieved from the local hospital registry. Based on the pre-therapeutic computer tomography (CT), we measured the total psoas muscle area, visceral adipose tissue area (VAT), subcutaneous adipose tissue area (SAT), and visceral-to-subcutaneous adipose tissue area ratio (VSR). In addition to the classical prognostic factors as T-stage, N-stage, gender, and treatment duration, we analyzed the impact of body composition on the prognosis in univariate and multivariate analyses. Results: Sarcopenia was not associated with increased mortality in anal cancer patients, whereas increased BMI (≥27 kg/m2) and VSR (≥0.45) were significantly associated with worsened overall survival and cancer-specific survival in both univariate and multivariate analyses. VSR—not BMI—was statistically higher in males. Sarcopenia and VSR ≥ 0.45 were associated with advanced T-stages. None of the body composition parameters resulted in a significant increase in treatment-related toxicities. Conclusion: BMI and visceral adiposity are independent prognostic factors for the survival of patients with anal cancer. Measurements to treat adiposity at the time of diagnosis may be needed to improve the survival outcomes for the affected patients.

Intensity modulated radiation therapy for elderly patients with esophageal cancer: Our experience.

The aim of this study was to discuss the treatment mode of radical radiotherapy for elderly patients with esophageal cancer. The clinical data of 136 elderly patients (≥60 years old) with esophageal cancer (EC) who received radical intensity-modulated radiotherapy in the Second Affiliated Hospital of Xi'an Jiaotong University from January 2015 to December 2019 were retrospectively analyzed. Cox risk model was used for multivariate prognostic analysis, and Kaplan Meier method was used to calculate progression free survival (PFS) and overall survival (OS). Cox regression analysis showed that ECOG score, basic diseases, T stage, radiation dose, radiation injury and chemotherapy were the prognostic factors of elderly patients. The median OS of the radiotherapy group, concurrent chemoradiotherapy group and sequential chemoradiotherapy group were 17, 41 and 10 months (p=0.009), respectively. The 3-year OS and PFS of concurrent intravenous chemotherapy and oral chemotherapy were 50%, 42.9% and 34.1%, 28.6% (p=0.641, p=0.702), respectively. The median OS of IFI and ENI were 23 and 24 months (p=0.219) and the local recurrence rate were 59.8% and 43.2% (p=0.069), respectively, but the incidence and mortality of radiation pneumonia and esophagitis in ENI were higher. The 3-year OS and PFS the low-dose group (≤60Gy) and high-dose group (>60Gy) were 19.1%, 40.4% and 14.9%, 29.2% (p=0.012, p=0.049), respectively. In conclusion, for elderly patients with inoperable EC, radical chemoradiotherapy should be considered a preferable selection. Among them, oral drugs and high-dose involved field irradiation exhibited better curative effects and safety.

Delineation of neck node levels for patients with locally advanced supraglottic cancer receiving radical intensity-modulated radiotherapy: across-sectional study in MainlandChina.

Background: To survey the diversity of clinical target volumes (CTVs) for locally advanced supraglottic cancer (LA-SGC) with radical radiotherapy in mainland China. Methods: Radiation oncologists from 30 provinces and four representative cases (T2N1, T3N2b, T4N0, T4N2c) were included. Results: High risk (HR)-CTV included involved and the lower adjacent level was followed by most physicians (n=160, 97.6%). In the N0-1 stage, whether contralateral levels II-III should be included in HR- or low risk (LR)-CTV was controversial. In the N2 stage, the bilateral levels II-IVb were included in LR-CTV (75-92.5% agreement). Levels Ib, V or VIb were included in CTV requiring certain conditions. Conclusion: Involved and lower adjacent levels were as HR-CTV. Whether bilateral levels II-IV are included in HR- or LR-CTV remaincontroversial.

Efficacy and safety of thalidomide in preventing oral mucositis in patients with nasopharyngeal carcinoma undergoing concurrent chemoradiotherapy: A multicenter, open-label, randomized controlled trial.

This multicenter clinical trial was designed to evaluate the efficacy and safety of thalidomide (THD) in preventing oral mucositis (OM) in patients with nasopharyngeal carcinoma (NPC) undergoing concurrent chemoradiotherapy (CCRT). Patients with locally advanced NPC were randomly assigned to either a THD group or a control group. All 160 patients received radical intensity-modulated radiotherapy plus cisplatin-based concurrent chemotherapy and basic oral hygiene guidance. Patients in the THD group received additional THD at the beginning of CCRT. The primary end points were the latency period and the incidence of OM. The secondary end points were mouth and throat soreness (MTS), weight loss, short-term efficacy, and adverse events. The median latency period of OM was 30 and 14 days in the THD and control groups, respectively (hazard ratio, 0.32; 95% confidence interval, 0.23-0.35; P < .0001). The incidence of OM and severe OM (World Health Organization grade 3 or higher) was significantly lower in the THD group than the control group (87.5% vs 97.5% [P = .016] and 27.5% vs 46.3% [P = .014], respectively). THD treatment also remarkably reduced the intensity of MTS and the degree of weight loss. In comparison with the control group, the incidence of nausea, vomiting, and insomnia was significantly decreased, whereas the incidence of dizziness and constipation was obviously increased in the THD group. The objective response rates 3 months after CCRT were similar between the groups. THD prolonged the latency period, reduced the incidence of OM, and did not affect the short-term efficacy of CCRT in patients with NPC. Oral mucositis is the most common complication of nasopharyngeal carcinoma during chemoradiotherapy; it decreases the patient's quality of life, and ideal mucosal protective agents are lacking. A few basic research and preclinical studies have shown that thalidomide may be an approach to ameliorating oral mucositis. The results of the current study confirm that thalidomide has a protective effect against oral mucositis in patients who have received chemoradiotherapy for nasopharyngeal carcinoma.

Comparison of Clinical Outcomes of Radical Prostatectomy versus IMRT with Long-Term Hormone Therapy for Relatively Young Patients with High- to Very High-Risk Localized Prostate Cancer

Simple SummaryThat the definitive optimal treatments for relatively young men (aged ≤ 65 years) with high- or very high-risk localized prostate cancer (HR/VHR-LPC) are radical prostatectomy (RP) or radiation plus antiandrogen therapy (RT-ADT) is controversial. To the best of our knowledge, our study is the first and largest to examine biochemical failure (BF), all-cause death, locoregional recurrence, and distant metastasis in relatively young men with HR/VHR-LPC as defined by National Comprehensive Cancer Network risk strata. After head-to-head propensity score matching was used to balance the potential confounders, a multivariable Cox proportional hazards regression model was used to analyze oncologic outcomes. In relatively young men with HR/VHR-LPC, RP and RT-ADT yielded similar oncologic outcomes and RP reduced the risk of BF compared with RT-ADT.That intensity-modulated radiotherapy (IMRT) plus antiandrogen therapy (IMRT-ADT) and radical prostatectomy (RP) are the definitive optimal treatments for relatively young patients (aged ≤ 65 years) with high- or very high-risk localized prostate cancer (HR/VHR-LPC), but remains controversial. We conducted a national population-based cohort study by using propensity score matching (PSM) to evaluate the clinical outcomes of RP and IMRT-ADT in relatively young patients with HR/VHR-LPC. Methods: We used the Taiwan Cancer Registry database to evaluate clinical outcomes in relatively young (aged ≤ 65 years) patients with HR/VHR-LPC, as defined by the National Comprehensive Cancer Network risk strata. The patients had received RP or IMRT-ADT (high-dose, ≥72 Gy plus long-term, 1.5–3 years, ADT). Head-to-head PSM was used to balance potential confounders. A Cox proportional hazards regression model was used to analyze oncologic outcomes. Results: High-dose IMRT-ADT had a higher risk of biochemical failure (adjusted hazard ratio [aHR] = 2.03, 95% confidence interval [CI] 1.56–2.65, p < 0.0001) compared with RP; IMRT-ADT did not have an increased risk of all-cause death (aHR = 1.2, 95% CI 0.65–2.24, p = 0.564), locoregional recurrence (aHR = 0.88, 95% CI 0.67–1.06, p = 0.3524), or distant metastasis (aHR = 1.03, 95% CI 0.56–1.9, p = 0.9176) compared with RP. Conclusion: In relatively young patients with HR/VHR-LPC, RP and IMRT-ADT yielded similar oncologic outcomes and RP reduced the risk of biochemical failure compared with IMRT-ADT.

Tumour volume and radiotherapy prolongation in locally advanced head and neck cancer patients treated with radical IMRT.

The relationship of tumour volume, radiotherapy treatment time and other prognostic factors affecting prognosis was evaluated. 184 patients with locally advanced head and neck cancer were treated with radical intensity modulated radiotherapy (IMRT) and compared retrospectively. In the multivariate analysis the overall survival was dependent on gross tumour volume (GTV), clinical stage (CS), radiotherapy treatment time (RTT) and p16 status. Local control was influenced by GTV, overall RTT and age. DFS was significantly affected by GTV, CS, RTT, p16 status and concomitant chemotherapy (CHT). The tumour volume and the radiotherapy treatment time were the most significant prognostic factors with the best outcomes in patients with GTV ≤ 55 cc and RTT ≤ 48 days (mean LC 8.1, DFS 7.1 and OS 6.4 years) and worst outcomes with GTV > 55 cc and RTT >48 days (mean LC 4.4, mean DFS 3.2 and mean OS 2.6 years).

Dynamic contrast-enhanced MRI predicts PTEN protein expression which can function as a prognostic measure of progression-free survival in NPC patients.

The objective of our study was to investigate whether a phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression was associated with dynamic contrast-enhanced MRI (DCE-MRI) parameters and prognosis in nasopharyngeal carcinoma (NPC). Two-hundred-and-forty-five (245) patients with NPC who underwent pretreatment biopsy, expression of PTEN detected by immunohistochemistry of biopsy, and radical intensity-modulated radiation therapy (IMRT) with or without chemotherapy were included. Tumor segmentations were delineated on pretreatment MRI manually. The pharmacokinetic parameters (Ktrans, Kep, Ve, and Vp) derived from dynamic contrast-enhanced MRI (DCE-MRI) using the extended Toft's model within the tumor segmentations were estimated. The following demographics and clinical features were assessed and correlated against each other: gender, age, TNM stage, clinical-stage, Epstein-Barr virus (EBV), pathological type, progression-free survival (PFS), and prognosis status. DCE parameter evaluation and clinical feature comparison between the PTEN positive and negative groups were performed and correlation between PTEN expression with the PFS and prognosis status using Cox regression for survival analysis were assessed. A significantly lower Ktrans and Kep were found in NPC tumors in PTEN negative patients than in PTEN positive patients. Ktrans performed better than Kep in detecting PTEN expression with the ROC AUC of 0.752. PTEN negative was associated with later TNM stage, later clinical-stage, shorter PFS, and worse prognosis. Moreover, N stage, pathological type, Kep, and prognostic status can be considered as independent variables in discrimination of PTEN negative expression in NPCs. PTEN negative indicated a shorter PFS and worse prognosis than PTEN positive in NPC patients. Ktrans and Kep derived from DCE-MRI, which yielded reliable capability, may be considered as potential imaging markers that are correlated with PTEN expression and could be used to predict PTEN expression noninvasively. Combined radiological and clinical features can improve the performance of the classification of PTEN expression.

Significance of boost dose for T4 nasopharyngeal carcinoma with residual primary lesion after intensity-modulated radiotherapy.

Previous studies showed poorer survival in T4 disease with residual lesion. To evaluate the efficacy and toxicity of a boost dose for T4 nasopharyngeal carcinoma (NPC), patients with a residual primary lesion after intensity-modulated radiotherapy (IMRT). 398 T4 NPC patients with residual primary lesions after radical IMRT were retrospectively reviewed. An IMRT boost dose of 4-6.75Gy was delivered to the residual lesions in 2-3 fractions. Propensity score matching (PSM) was applied to balance potential confounders between groups (ratio, 1:2). The presence of Epstein-Barr virus (EBV) DNA in plasma after IMRT was used for risk stratification. Patients who received boost radiation had significantly improved overall survival (OS) and local recurrence-free survival (LRFS) compared with those who did not (all P < 0.05). In the matched cohort, 3-year OS was 86.6% in the boost radiation group and 72.7% in the non-boost group (P = 0.022). Three-year LRFS was 93.4% in the boost radiation group and 83.5% in the non-boost group (P = 0.022). In the subgroup analysis, boost dose was shown to significantly improve 3-year OS (88.0% vs. 74.1%, P = 0.021) in the low-risk group (with undetectable plasma EBV DNA after IMRT). The administration of a boost dose also improved 3-year OS in the high-risk group (with detectable plasma EBV DNA after IMRT) (66.7% vs. 60.0%, P = 0.375). Multivariate analysis demonstrated that boost dose was the only protective prognostic factor. The addition of a boost dose for T4 NPC patients with residual primary lesion after radical IMRT provides satisfactory tumor control and clinical benefit. Additional timely and effective strengthening treatments are recommended for patients with detectable levels of plasma EBV DNA after radiotherapy.

Effect of tumor and normal lung volumes on the lung volume–dose parameters of IMRT in non–small-cell lung cancer

OBJECTIVES:To explore the effect of tumor and normal lung volumes on lung volume-dose parameters in patients with non-small-cell lung cancer (NSCLC) who had undergone intensity-modulated radiation therapy (IMRT).METHODS:The clinical data of 208 patients with NSCLC who underwent radical IMRT between June 2014 and June 2018 were retrospectively analyzed. A regression model curve was used to evaluate the effect of tumor and normal lung volumes on normal lung relative volumes receiving greater than 5 and 20 Gy (V5, V20), on mean lung dose (MLD), and on absolute volumes spared from greater than 5 and 20 Gy (AVS5, AVS20).RESULTS:The V5, V20, and MLD of the bilateral lung were fitted to a quadratic equation curve with the change in tumor volume, which increased initially and then decreased when the tumor volume increased. The V5, V20, and MLD of the lung reached their apex when the tumor volumes were 288.07, 341.69, and 326.83 cm3, respectively. AVS5 and AVS20 decreased in a logarithmic curve with an increase in tumor volume. The V5, V20, and MLD of the small normal lung volume group were all significantly higher than those of the large normal lung volume group (p<0.001, p=0.004, p=0.002). However, the AVS5 and AVS20 of the small normal lung volume group were all significantly lower than those of the large normal lung volume group (p<0.001).CONCLUSION:The effects of tumor volume and normal lung volume on dose-volume parameters should be considered. AVS5 is an important supplementary dose limitation parameter for patients whose tumor volume exceeds a certain boundary value (approximately 300 cm3).

Development and Validation of Web-Based Nomograms to Precisely Predict Survival Outcomes of Non-metastatic Nasopharyngeal Carcinoma in an Endemic Area.

PurposeThis study aimed to develop web-based nomograms to precisely predict survival outcomes in patients with non-metastatic nasopharyngeal carcinoma (NPC) in an endemic area.Materials and MethodsA total of 10,126 patients who underwent radical intensity-modulated radiotherapy at Sun Yat-sen University Cancer Center (SYSUCC) from 2009 to 2015 were analyzed. We assigned patients into a training cohort (SYSUCC-A, n=6,751) and an internal validation cohort (SYSUCC-B, n=3,375) based on computer-generated random numbers. Patients collected from Wuzhou Red Cross Hospital (WZRCH) between 2012 and 2015 were used as the independent external validation cohort (WZRCH, n=450). Concordance index (C-index) was used to determine predictive accuracy and discriminative ability for the nomogram. The web-based clinicopathologic prediction models for predicting survival were based on Cox regression.ResultsThe C-indexes for SYSUCC-A, SYSUCC-B, and WZRCH cohorts for the established nomograms to predict 3-year overall survival (OS) was 0.736, 0.715, and 0.691. Additionally, C-indexes to predict 3-year distant metastasis-free survival (DMFS) was 0.717, 0.706, and 0.686, disease-free survival (DFS) was 0.713, 0.697, and 0.656, local relapse-free survival was 0.695, 0.684, and 0.652, and regional relapse-free survival was 0.672, 0.650, and 0.616. The calibration plots showed great agreement between nomogram-predicted 3-year survival outcomes and actual 3-year survival outcomes. Moreover, C-indexes of the nomograms for OS, DMFS, and DFS were significantly superior than TNM stage (p < 0.001 for all).ConclusionThese user-friendly nomograms can precisely predict survival endpoints in patients with non-metastatic NPC. They may serve as a useful tool for providing patient counseling and help physicians to make individual follow-up plans.

The role of PET-CT in staging anal cancers planned for radical intensity-modulated radiotherapy: a single centre experience

The role of PET-CT in staging anal cancers planned for radical intensity-modulated radiotherapy: a single centre experience

Intensity-modulated Radiation Therapy (IMRT) May Reduce Diarrhea With Similar Treatment Efficacy Even In Japanese Treatment Strategy For Cervical Cancers

The RTOG 1203 trial showed that IMRT after hysterectomy could reduce acute radiation enteritis (ARE) compared to 3-dimensional conformal radiotherapy (3DCRT). However, it should be investigated whether IMRT could reduce ARE in radical radiotherapy for cervical cancers, considering the inter- and intra-fractional motions of the uterus (5-15 mm) and larger target volume. In Japan, treatment strategy for cervical cancers differs from that of other countries. The intestine is shielded during whole-pelvic irradiation (WPI) and brachytherapy starts earlier. Thus, even in 3DCRT, the ARE incidence can be lower than in other countries. We applied radical IMRT for cervical cancers using tomotherapy and investigated whether the IMRT protocol could reduce ARE and other toxicities. We reviewed patients with cervical cancers treated at 3 institutions that employed the same protocol. In the protocol, patients with UICC 8th stage IB-IVA cervical cancers received radical WPI ± paraaortic irradiation with 45-50.4 Gy delivered at a daily fraction of 1.8 Gy five times a week. Platinum-containing chemotherapy was delivered to ≥ stage III or tumors with ≥ 4 cm in the maximum diameter. After 20-30 Gy of WPI depending on the stage, the rectum, bladder and intestine were shielded and intracavitary brachytherapy (2-4 times at a point A dose of 5-6 Gy) was carried out. In IMRT, a block structure was contoured instead of the center shielding in 3DCRT. The block structure median dose was reduced to ≤ 0.9 Gy/fr. From 2007 to 2011, 3DCRT was used. From 2012, the IMRT protocol was introduced. We compared the IMRT and 3DCRT groups. All patients treated with the protocols were analyzed except patients with: 1) previous history of hysterectomy or radiotherapy and 2) small cell cancer. ARE was defined as the increase in stool of 4–6 times per day over the baseline. In total, 169 patients were treated according to the protocols. Of them, IMRT was delivered to 93 (median age, 63 years) and 3DCRT to 76 (61 years). Chemotherapy was administered to 73 in the IMRT group and 50 in the 3DCRT group (p = 0.08). Lymph node metastases were seen in 44 in the IMRT group and 26 in the 3DCRT group (p = 0.12). The 3-year overall survival and locoregional recurrence rates after IMRT were 84% and 17%, respectively. In the 3DCRT group, these rates were 70% and 20%, respectively. No difference was seen between the 2 groups (p > 0.2). ARE occurred less frequently in the IMRT group than in the 3DCRT group (17/93 vs 24/76, p < 0.05). Grade 3 toxicities were observed in 5 in the IMRT group (rectal bleeding 2, sigmoid colon stenosis 1, bladder tamponade 2) and in 3 in the 3DCRT group (rectal bleeding 1, small intestinal perforation 2) (p = 0.73). There was no ≥ grade 4 toxicity in both groups. Even in the Japanese treatment strategy for cervical cancers, use of IMRT may reduce ARE with similar treatment efficacy.

Extranodal Expansion Of The Lymph Nodes Is An Effective Predictor Of Distant Metastasis Of Nasopharyngeal Carcinoma After Radical Radiotherapy And Chemotherapy

Extranodal extension (ENE) of the lymph nodes is a criterion for advanced nodal staging of oropharyngeal and hypopharyngeal carcinoma. The purpose is to investigate whether ENE is a factor affecting distant metastasis of nasopharyngeal carcinoma after radical radiotherapy and chemotherapy. From January 2009 to December 2014, 318 patients of NPC after radical radiotherapy and chemotherapy were enrolled. All patients received radical intensity-modulated radiotherapy. Concurrent chemotherapy was cisplatin intravenous drip every 3 weeks for 4-6cycles.MRI was retrospectively reviewed in all patients and the ENE of the lymph nodes was evaluated in patients with metastatic lymph nodes. According to the tendency of disease metastasis, patients were divided into ascending and descending types. Ascending type (Type A,T3-4N0-1) was defined as advanced local disease and early-stage cervical lymph-node involvement; advanced lymph-node metastases but early -stage local disease was classified as descending type (Type D,T1-2N2-3). Kaplan-Meier methods and Cox proportional hazard models were used to evaluate the impact of different types on distant metastasis free survival. The 5-year distant metastasis-free survival (DMFS) rate of all patients was 85%. There were 143 patients with type A and 175 patients with type D. Compared with type A, type D had worse 5-year DMFS (95% vs 78%; P < 0.05). For type A, univariate analysis and multivariate analysis suggested that ENE was closely related to distant metastasis (P < 0.05). Compared with negative ENE, ENE positive had a higher probability of metastasis within 5 years (DMFS: 99% vs 66.7%; P < 0.05). The independent prognostic factors of type D distant metastasis are ENE and the number of positive lymph nodes. ENEpositive is more likely to have distant metastasis than ENEnegative (DMFS: 84% vs 62.7%). Compared with patients with more than 4 positive lymph nodes, patients with less than 4 positive lymph nodes have significantly better DMFS (83.7% vs 90.9%; P < 0.05 for all). Patients with type D was more likely to metastasize than type A, but no matter how it was typed, ENE was an independent factor affecting distant metastasis and could be considered as a new standard for NPC lymph node staging.

Prognostication of Half-Life Clearance of Plasma EBV DNA in Previously Untreated Non-metastatic Nasopharyngeal Carcinoma Treated With Radical Intensity-Modulated Radiation Therapy.

Introduction: The prognostic role of plasma Epstein–Barr virus (EBV) DNA clearance when intensity-modulated radiotherapy (IMRT) and the 8th edition of American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) TNM Staging Classification are fully implemented remains undeciphered. We investigated if its half-life clearance during radical treatment for non-metastatic nasopharyngeal carcinoma (NPC) was an early prognosticator.Patients and methods: Patients with previously untreated non-metastatic NPC were prospectively treated with radical IMRT and concurrent chemotherapy +/– induction/adjuvant chemotherapy from 2014 to 2018. Their plasma EBV DNA was measured immediately before treatment followed by weekly schedules until 0 copy/ml in two consecutive measurements. Cox regression models were employed to identify prognostic factors.Results: Forty-five patients were prospectively recruited and analyzed. After a median follow-up of 30.3 months, 2 (4.5%), 1 (2.3%), and 6 (13.6%) patients experienced local, regional, and distant relapses, respectively. The median half-life clearance of plasma EBV DNA was 7.92 days. Those with half-life clearance of >15 days had a worse 3-years progression-free survival (PFS) (79.5 vs. 25.0%, p = 0.005), distant metastasis-free survival (DMFS) (85.0 vs. 31.3%, p = 0.009), and overall survival (OS) (91.3 vs. 75.0%, p = 0.024) when compared to those with a shorter half-life. Multivariable analyses demonstrated that only half-life (>15 days) was prognostic of DMFS [HR (95% CI): 4.91 (1.31; 18.39), p = 0.01] and OS [HR (95% CI): 5.24 (1.06; 26.05)] while half-life (>15 days) [HR (95% CI): 5.14 (1.28; 22.73), p = 0.02] and sum of pretreatment gross tumor volumes of the primary nasopharyngeal tumor and the radiologically positive neck nodes (GTV_P+N) [HR (95% CI): 1.01 (1.00; 1.03), p = 0.02] were prognostic of PFS.Conclusion: The half-life clearance of plasma EBV DNA was prognostic in non-metastatic NPC staged and treated in the contemporary era. Earlier biomarker surveillance during treatment should be considered.Clinical Trial Registration: This study has been registered with ClinicalTrials.gov (Identifier: NCT03830996).

Lymph node-to-primary tumor standardized uptake value ratio on PET predicts distant metastasis in nasopharyngeal carcinoma.

To investigate the prognostic value of the relative maximum standardized uptake value (SUV) ratio between neck lymph node and primary tumor (NTR) measured by pretreatment 18F-FDG PET in patients with nasopharyngeal carcinoma (NPC). We retrospectively reviewed patients with non-disseminated NPC who underwent PET scans before radical intensity-modulated radiotherapy (IMRT). Receiver operating characteristic analysis was performed to identify the optimal cut-off value for NTR. The prognostic value of NTR for distant metastasis-free survival (DMFS) was evaluated using Kaplan-Meier method for survival analyses and Cox regression for multivariable analysis. Among the 437 eligible patients, the median follow-up time was 62.9 (range, 2.1-113.0) months. Patients with high NTR (NTR>0.9181) experienced significantly worse DMFS (5-year 80.5% vs. 91.6%, P<0.001). In the subgroup analysis, we found that patients with high NTR had significantly lower DMFS in T1-2 category (5-year 86.1% vs. 98.1%, P=0.002), T3-4 category (5-year 71.5% vs. 86.2%, P=0.010), N2-3 category (5-year 75.3% vs. 86.2%, P=0.048), and stage IVA-B (5-year 69.8% vs. 85.4%, P=0.012). Multivariable analysis showed that NTR was an independent prognostic factor for DMFS (HR 2.20, 95% CI 1.20-4.03, P=0.011). Pretreatment NTR is an easily accessible but potential prognosticator for DMFS in NPC patients treated by IMRT, which may help in providing more personalized treatment or designing future clinical trials.