PURPOSE:To provide a comprehensive analysis of conditional survival (CS) and dynamic failure hazards in oral cavity squamous cell carcinoma (OCSCC), enhancing prognostic understanding and facilitating more individualized treatment strategy and surveillance. METHOD:Patients with non-metastatic OCSCC undergoing surgery between 1999 and 2018 were retrospectively analyzed. Overall survival (OS), disease-free survival (DFS), conditional OS (COS), and conditional DFS (CDFS) were calculated. Annual hazards, including death, progression, and stage-specific risks, were estimated using Kernel-based methods. RESULTS:Among 700 patients (median follow-up: 97.6 months), the 5-year OS and DFS were 68.3 % and 62.0 %, respectively. The 5-year COS improved from 71 % after one year to 86 % after five years, while the 5-year CDFS increased from 76 % to 87 %. Annual hazard rates for death and progression peaked in the first two years post-surgery, with death hazard declining from 9.8 % to 3.3 % and progression hazard decreasing from 20.0 % to 2.9 % by the fifth year. Stage-specific death hazards peaked at varying timings: the second year for stages I/II, the third year for stage III, and the first two years for stage IV. Progression hazards peaked in the first year for all stages, with stage IV showing the highest risk at 32.0 %, decreasing to ∼ 4 % by the fourth year. CONCLUSION:This study provides an updated overview of CS and dynamic failure hazards in OCSCC, particularly emphasizing the high progression hazard in stage IV patients during the first year. These findings support tailored treatment strategies and rigorous early surveillance to improve outcomes.

BACKGROUND:Regional failure (RF) in oral cavity squamous cell carcinoma (OCSCC) is associated with poor outcomes, yet its detailed pattern and its relationship with corresponding neck management strategies remain inadequately defined. This study aims to provide insights for optimizing neck management in OCSCC patients through a comprehensive analysis of RF patterns. METHODS:A retrospective review was conducted on patients with OCSCC who underwent radical surgery with or without postoperative radiotherapy (PORT) between 2015 and 2018. Detailed mapping of the initial metastasis and RF patterns was performed and correlated with the corresponding neck management approaches. RESULTS:A total of 147 patients and 294 necks were included in the analysis. RF was identified as the predominant pattern of failure (5-year rate: 19.8%), with pN+ being the most notable risk factor for regional failure-free survival (RFFS). Compared to the Surgery group, the Surgery+PORT group demonstrated a significantly lower RF rate beyond the dissected region (6.5% vs. 20.0%, p = 0.03) and a numerically lower RF rate beyond the upper neck (5.2% vs. 12.9%, p = 0.10). In dissected necks, RF at level IV accounted for 47.3% of all RF occurrences. The "dissected and irradiated" necks exhibited a lower RF rate than the "dissected-alone" necks (8.7% vs. 13.4%), particularly at level IV (2.2% vs. 8.5%) and Vb (1.1% vs. 3.7%). When compared to the "untreated" necks, the "irradiated-alone" necks showed reduced RF at almost all levels. CONCLUSIONS:The significant rate of RF in the lower neck warrants particular attention in OCSCC management. Prophylactic irradiation to the lower neck may play a critical role in enhancing regional control and improving patient outcomes.

Objective: To investigate the caudal distribution pattern of metastatic neck lymph nodes (LNs) in nasopharyngeal carcinoma (NPC) and the prognostic significance of nodal spread distances (SDs). Materials and methods: NPC patients with neck metastatic LNs were enrolled. The most caudally located LNs were marked. SD was defined as the distance from marked LNs to the lateral process of the atlantoaxial spine (LPC1). Univariate and multivariate analyses were performed to assess association between MRIidentified nodal features and survival. Harrell's concordance index (C-index) and area under the curve (AUC) were used to compare AJCC (8th edition) N staging with the proposed N staging. Survival after induction chemotherapy plus concurrent chemoradiotherapy (IC + CCRT) versus CCRT alone was compared between different SD groups. Results: A total of 1907 LNs (1164 patients) were contoured. SD > 7 cm was an independent predictor of overall survival (OS), distant metastasis-free survival (DMFS), and progression-free survival (PFS), with hazard ratios of 1.725, 1.553 and 1.414, respectively. When patients with SD > 7 cm were upgraded one N stage higher, the proposed N classification showed better stratification in OS, DMFS, and PFS between N1 and N2 stages. C-indices and AUCs of the proposed N staging were superior to AJCC N staging. IC + CCRT showed negative effect in N1-2 patients with SD <= 7 cm but improved OS in those with SD > 7 cm. Conclusion: SD of metastatic LNs can predict survival in NPC. Integration of SD into AJCC N staging could improve its prognostic value and help identify patients requiring IC. (c) 2022 Elsevier B.V. All rights reserved. Radiotherapy and Oncology 179 (2023) 109443

PURPOSETo develop and validate a nomogram integrating lymph node ratio (LNR) to predict cancer-specific survival (CSS) and assist decision making for postoperative management in nonmetastatic oral cavity squamous cell carcinoma (OCSCC).MATERIALS AND METHODSWe retrospectively retrieved 6,760 patients with OCSCC primarily treated with surgery from surveillance, epidemiology, and end results database between 2010 and 2015. They were randomly divided into training and validation cohorts. Performance of the nomogram was evaluated by calibration curve, consistency index, area under the curve, and decision curve analysis and was compared with that of the LNR, positive lymph nodes (PLN) and tumor node metastasis (TNM) staging. According to the individualized nomogram score, patients were classified into three risk cohorts. The therapeutic efficacy of postoperative radiotherapy and chemotherapy was evaluated in each cohort.RESULTSThe nomogram incorporated six independent variables, including race, tumor site, grade, T stage, PLN, and LNR. Calibration plots demonstrated a good match between the predicted and observed CSS. C-indices for training and validation cohorts were 0.746 (95% CI, 0.740 to 0.752) and 0.726 (95% CI, 0.713 to 0.739), compared with 0.687, 0.695, and 0.669 for LNR, PLN, and TNM staging, respectively ( P < .001). Decision curve analyses confirmed that nomogram showed the best performance in clinical utility. Postoperative radiotherapy presented survival benefit in medium-and high-risk groups but showed a negative effect in the low-risk group. Chemotherapy was only beneficial in the high-risk group.CONCLUSIONThe LN status-incorporated nomogram demonstrated good discrimination and predictive accuracy of CSS for patients with OCSCC and could identify those most likely to benefit from adjuvant therapy.

Abstract Background The main challenge in follow-up duration of patients with brain metastases after stereotactic radiotherapy is to distinguish between pseudo-progression and tumor recurrence. The objective of this study is to retrospectively analyze the predictive factors. Methods The study included 123 patients with enlarged brain metastases after hypo-fractionated radiotherapy in our center from March 2009 to October 2019, and the baseline clinical features, radiotherapy planning parameters, and enhanced magnetic resonance imaging before and after radiation therapy were analyzed. Logistic regression was performed to compare the differences between groups. Independent risk factors with P < 0.05 and associated with recurrence were used to establish a nomogram prediction model and validated by Bootstrap repeated sampling, which was validated in an internal cohort (n = 23) from October 2019 to December 2021. Results The median follow-up time was 68.4 months (range, 8.9–146.2 months). A total of 76 (61.8%) patients were evaluated as pseudo-progression, 47 patients (38.2%) were evaluated as tumor recurrence. The median time to pseudo-progression and tumor recurrence were 18.3 months (quartile range, 9.4–27.8 months) and 12.9 months (quartile range, 8.7–19.6 months) respectively. Variables associated with tumor recurrence included: gross tumor volume ≥ 6 cc, biological effective dose < 60 Gy, target coverage < 96% and no targeted therapy. The area under curve values were 0.730 and 0.967 in the training and validation cohorts, respectively. Thirty-one patients received salvage therapy in the tumor recurrence group. The survival time in pseudo-progression and tumor recurrence groups were 66.3 months (95% CI 56.8–75.9 months) and 39.6 months (95% CI 29.2–50.0 months, respectively; P = 0.001). Conclusions Clinical and dosimetry features of hypo-fractionated radiation therapy based on enhanced brain magnetic resonance can help distinguish pseudo-progression from tumor recurrence after hypo-fractionated radiotherapy for brain metastases. Gross tumor volume, biological effective dose, target coverage, and having received targeted therapy or not were factors associated with the occurrence of tumor recurrence, and the individual risk could be estimated by the nomogram effectively.

Abstract Purpose: Multiple brain metastases (BMs) remain a therapeutic challenge. Helical tomotherapy (HT) is a novel equipment which has shown favorable dosimetric properties in previous studies. The aim of this single institutional phase II trial was to investigate the feasibility and toxicity of hypofractionated radiotherapy (HFRT) with or without simultaneous whole brain radiotherapy (WBRT) by HT in treating patients with multiple BMs. Methods:Patients with at least 3 BMs were enrolled. All the patients were treated with HT. The prescribed dose was 40 Gy in 20 fractions for WBRT and 60 Gy in 20 fractions for BMs simultaneously. For patients who had prior WBRT or refusing WBRT, focal HFRT for the lesions with optimized doses based on tumor volumes and locations were given. The primary endpoint was 1y-intracranial progression free survival (IPFS). Results: Between September 2014 and June 2017, 69 patients were enrolled and finally been analyzed. The median follow-up time was 40.1 months. The 1-year IPFS rate was 80.5%. The median survival time was 18.1 months (95% CI, 15.5- 20.7). The 1-year local control, overall survival and brain metastasis-specific survival rates were 96.4%, 71.0% and 94.6%, respectively. The 2-year rates were 87.6%, 51.1% and 39.1%, respectively. Only 1 patient (1.4%) had Grade 3 hematological toxicity and the radiation necrosis rate was 2.9%. Conclusion: Helical tomotherapy was well tolerated and could significantly extend IPFS compared with historical controls in multiple BMs.

Abstract Purpose To evaluate prognosis for reducing postoperative radiotherapy (PORT) dose to lymph node levels of supraglottic cancer (SC) on real-world data. Method and materials Patients were derived from two cancer centers. In center 1, the involved nodal levels (high-risk levels, HRL) and the next level received a dose of 60.06 Gy/1.82 Gy per fraction, while the other uninvolved levels (low-risk levels, LRL) received 50.96 Gy/1.82 Gy per fraction. In center 2, all received 50 Gy/2 Gy per fraction. The rates of high-risk levels control (HRC), regional control (RC), overall survival (OS), progression-free survival (PFS) and distant metastasis-free survival (DMFS) were calculated by Kaplan–Meier method. Result Totally, 124 patients were included (62 in center 1, 62 in center 2). Most patients (106, 85.5%) had a stage T3/N + tumor. The median follow-up was 45 months (range 1–163 months). There were no significant differences in terms of OS (p = 0.126), RC (p = 0.514), PFS (p = 0.195) and DMFS (p = 0.834). Most regional recurrences (4, 80%) occurred within three years of treatment, and all occurred within the target volumes. No regional failure occurred in HRL in center 1, while three (3/4) failures occurred in center 2. Dose reduction prescription to HRL led to a lower HRC rate (100% vs. 90.6%, p = 0.009). While the rates of LRL control (98.4%) were equal between the two centers. Conclusion Compared with a standard dose, the reduced dose to involved nodal levels showed inferior regional control for PORT, while uninvolved nodal levels showed equal outcomes. A dose of 50 Gy for HRL may be an unfavorable treatment option for SC.

Objective:To establish the first Mini-Formative Evaluation of Radiation Oncology (Mini-FERO) scale in China and evaluate its preliminary application value in the standardized training for radiation oncology resident physicians.Methods:Based on the educational curriculum and examination requirements for the standardized training for radiation oncology resident physicians, as well as the standardized Mini-Clinical Evaluation Exercise (Mini-CEX) scale commonly used in clinical practice, the Mini-Formative Evaluation of Radiation Oncology (Mini-FERO) scale was developed to facilitate the standardized training for resident physicians in the field of radiation oncology. In this prospective study, a randomization method using a random number table was employed to select a cohort of 26 resident physicians who completed their rotations in Department of Radiation Oncology at the Cancer Hospital, Chinese Academy of Medical Sciences from March 1, 2021 to December 31, 2021. The Mini-FERO scale was administered in the initial, middle, and final stages during the rotation period. The differences in evaluation scores before and after the assessments were analyzed by paired t-test. Furthermore, participating resident physicians and supervising teachers provided satisfaction ratings, and a comprehensive evaluation of the Mini-FERO scale was conducted. Results:The average scores of the three examinations of 26 resident physicians demonstrated a successive improvement, with individual performance in each assessed category also showing progressive enhancement. The second evaluation exhibited a more pronounced score increase compared to the first evaluation, with a mean improvement of (1.43±1.02) points ( t=7.13, P<0.001); while the third evaluation had a mean improvement of (0.41±0.50) points ( t=4.07, P<0.001) compaired to the second evaluation, with a mean difference of (1.02±1.15) points between the two ( t=4.53, P<0.001). The average time required for the assessments was (34.31±24.46) min. Overall satisfaction ratings from the evaluated resident physicians for the Mini-FERO scale were (8.42±0.85) points, and supervising teachers reported an overall satisfaction rating of (8.45±0.85) points. The satisfaction rate was 96% (25/26). Conclusions:In this study, the Mini-FERO scale was successfully developed and validated in the context of clinical teaching practice for radiation oncology resident physicians. The Mini-FERO scale is proven to be a feasible tool for assessing the gradual improvement of resident physicians throughout their learning process in the field of radiation oncology. Importantly, it offers the advantages of short assessment time, thereby avoiding additional burden on supervising teachers. The adoption of the Mini-FERO scale addresses current limitations of lacking of formative evaluation in the standardized training for radiation oncology resident physicians.

Purpose To define the clinical characteristics of irradiation-induced nasopharyngeal necrosis (INN) after intensity-modulated radiotherapy (IMRT) and identify the influence of treatment strategies on INN in primary nasopharyngeal carcinoma (NPC) patients. Patients and methods From 2008 to 2019, NPC patients pathologically diagnosed with INN after primary IMRT were reviewed. Those patients were matched with propensity scores for patients without INN in our center. The impact of treatment strategies on INN occurrence was assessed using univariate and multivariate logistic regression analysis. Results The incidence rate of INN was 1.9% among the primary NPC population, and 53 patients with INN were enrolled. Headache and foul odor were the main symptoms, and 71.7% of cases had pseudomembrane during or at the end of radiotherapy. All patients were in early or middle stage INN, and no one presented with skull-based osteoradionecrosis. Then 212 non-INN patients were included based on propensity scores match. Overall survival (p = 0.248) and progression-free survival (p = 0.266) curves were similar between the INN and non-INN groups. Treatment strategies including combining chemotherapy or molecular targeted therapy with radiotherapy were not associated with INN occurrence, while boost dose (OR 7.360; 95% CI 2.301-23.547; p = 0.001) was a predictor factor for it. However, the optimal threshold for an accumulated dose to predict INN's occurrence was failed to determine. Conclusion In the IMRT era, the severity of INN in primary NPC patients is lessened. This study showed that treatment strategies contributed little to develop INN, while the accumulated dose of radiation may relate to its occurrence.

PurposeThis study aims to investigate the prognostic value of composition and spatial architecture of tumor-infiltrating lymphocytes (TILs) as well as PDL1 expression on TILs subpopulations in nasopharyngeal carcinoma (NPC).MethodsA total of 121 patients with NPC were included and divided into two groups: favorable (n = 68) and unfavorable (n = 53). The archived tumor tissues of the included patients were retrieved, and a tissue microarray was constructed. The density and spatial distribution of TILs infiltration were analyzed using the multiplex fluorescent immunohistochemistry staining for CD3, CD4, CD8, Foxp3, cytokeratin (CK), PDL1, and 4′,6-diamidino-2-phenylindole (DAPI). The infiltration density of TILs subpopulations and PDL1 expression were compared between the two groups. The Gcross function was calculated to quantify the relative proximity of any two types of cells. The Cox proportional hazards regression model was used to identify factors associated with overall survival (OS) and disease-free survival (DFS).ResultsThe densities of regulatory T-cells (Tregs), effector T-cells (Teffs), PDL1+ Tregs, and PDL1+ Teffs were significantly higher in patients with unfavorable outcomes. PDL1 expression on tumor cells (TCs) or overall TILs was not associated with survival. Multivariate analysis revealed that higher PDL1+ Tregs infiltration density was independently associated with inferior OS and DFS, whereas Tregs infiltration density was only a prognostic marker for DFS. Spatial analysis revealed that unfavorable group had significantly stronger Tregs and PDL1+ Tregs engagement in the proximity of TCs and cytotoxic T lymphocyte (CTLs). Gcross analysis further revealed that Tregs and PDL1+ Tregs were more likely to colocalize with CTLs. Moreover, increased GTC : Treg (Tregs engagement surrounding TCs) and GCTL : PDL1+ Treg were identified as independent factors correlated with poor outcomes.ConclusionTILs have a diverse infiltrating pattern and spatial distribution in NPC. Increased infiltration of Tregs, particularly PDL1+ Tregs, as well as their proximity to TCs and CTLs, correlates with unfavorable outcomes, implying the significance of intercellular immune regulation in mediating disease progression.

Objective:To evaluate the prognostic value of pretreatment systemic immune-inflammation index (SII) and lactate dehydrogenase (LDH) in non-metastatic nasopharyngeal carcinoma (NPC).Methods:We retrospectively collected the data of 839 patients with non-metastatic NPC from National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Sun Yat-sen University Cancer Center between January 2007 and October 2015. All patients received intensity modulated radiation based treatment. Optimal cutoff value of SII and LDH were determined by X-title software. The association between SII, LDH and clinical prognosis of non-metastatic NPC patients were analyzed. Kaplan-Meier method was used for survival analysis, and Log rank test was used for comparison of survival rates between groups. Propensity score matching (PSM) analysis was carried out to minimize the effects of confounding factors. The risk stratification model of prognosis by combining N stage, SII and LDH was constructed to compare the prognosis of patients in high risk group, middle risk group and low risk group, and the receiver operating characteristic (ROC) curve analysis was used to evaluate its prognostic value.Results:The optimal cutoff value of SII is 447.2×10 9/L for predicting the 5-year overall survival (OS) of NPC patients, and the best cutoff value of LDH is 198.9 U/L. The proportion of patients with stage T3-4 and stage III-IVB in high SII group was higher than that in low SII group ( P<0.001). Multivariate Cox regression analysis showed that N stage, SII and LDH were independent factors of OS, progression-free survival (PFS) and distant metastasis-free survival (DMFS) of NPC patients (N stage, HR=1.705, 95% CI: 1.247-2.332; HR=1.755, 95% CI: 1.342-2.295; HR=2.161, 95% CI: 1.515-3.082. SII, HR=1.525, 95% CI: 1.097-2.119; HR=1.518, 95% CI: 1.150-2.004; HR=1.837, 95% CI: 1.272-2.653. LDH, HR=2.041, 95% CI: 1.403-2.968; HR=1.725, 95% CI: 1.233-2.414; HR=2.492, 95% CI: 1.690-3.672, respectively). After PSM, SII was still an independent prognostic factor of OS, PFS and DMFS in NPC patients ( HR=1.52, 95% CI: 1.09-2.12; HR=1.52, 95% CI: 1.15-2.00; HR=1.82, 95% CI: 1.26-2.63, respectively). Combined with N 2-3 stage, SII (>447.2×10 9/L), and LDH (>198.9 U/L), patients were divided into high-(3 risk factors), intermediate- (2 risk factors) and low-risk (0-1 risk factors) groups. The 5-year OS rates of patients in low-, intermediate- and high-risk groups were 86.1%, 79.8% and 41.2% respectively, the 5-year PFS rates were 80.7%, 70.2% and 33.9% respectively, and the 5-year DMFS rates were 88.9%, 79.2% and 47.5% respectively. There were significant differences in OS, PFS and DMFS among these three groups ( P<0.001). Distant metastasis was the main failure pattern in low-, intermediate- and high-risk groups, and the highest rate of distant metastasis was 83.3% (15/31) in high-risk group. ROC curve of the risk stratification model for predicting 5-year OS of NPC patients is 0.610, which is higher than TNM stage (0.609), SII (0.574) and LDH (0.558). Conclusions:Pretreatment SII and LDH are significantly correlated with the prognosis of patients with non-metastatic NPC. The combination of SII, LDH and N stage can stratify the prognostic risk of NPC patients. The risk stratification model can enhance the accuracy of prognosis.

Abstract PURPOSE The main challenge in follow-up duration of patients with brain metastases after stereotactic radiotherapy is to distinguish between pseudo-progression and tumor recurrence. The objective of this study is to retrospectively analyze the predictive factors. METHODS The study included 123 patients with enlarged brain metastases after hyper-fractionated radiotherapy in our center from 2009 to 2019, and the baseline clinical features, radiotherapy planning parameters, and enhanced magnetic resonance imaging before and after radiation therapy were analyzed. Logistic regression was performed to compare the differences between groups. independent risk factors with P < 0.05 and associated with recurrence was used to establish a predicting nomogram and validated by Bootstrap in internal cohort. RESULTS The median volume of lesions was 8.4 cc. The median follow-up time was 68.4 months (interquartile range [IQR], 30.4 – 63.2 months). A total of 76 (61.8%) patients were evaluated as pseudo-progression, 47 patients (38.2%) were evaluated as tumor recurrence. The median time to tumor recurrence and pseudo-progression were 12.9 months (IQR, 8.7 – 19.6 months) and 18.3 months (IQR, 9.4 – 27.8 months) respectively. Variables associated with tumor recurrence included: gross tumor volume ≥ 6 cc, biological effective dose < 60 Gy, target coverage < 96% and no targeted therapy. The area under curve value was 0.730 and mean absolute error in calibration curve was 0.041. Sixty-one patients received salvage therapy, including re-irradiation (n = 32, 26.0%), surgical resection (n = 22, 17.9%) or systemic therapy (n = 22, 17.9%). The survival time in pseudo-progression and tumor recurrence groups were 66.3 months (95% CI, 56.8 – 75.9 months) and 39.6 months (95% CI, 29.2 – 50.0 months, respectively; P = 0.001). CONCLUSIONS Clinical and dosimetry features of hyper-fractionated radiation therapy based on enhanced brain magnetic resonance can help distinguish pseudo-progression from tumor recurrence after hyper-fractionated radiotherapy for brain metastases. And the individual risk could be estimated by the nomogram effectively.

Objective: This study aimed to evaluate the prognostic value of the pretreatment systemic immune-inflammation index (SII) in non-metastatic nasopharyngeal carcinoma (NPC).Methods: We retrospectively analyzed the data of 839 patients with non-metastatic NPC recruited from two independent institutions. The training-set cohort and the external validation-set cohort was comprised of 459 and 380 patients from each institution, respectively. The optimal cut-off value of SII was determined, and a prognostic risk stratification model was developed based on the training cohort and further assessed in the validation cohort. The propensity score matching (PSM) method was applied to minimize the confounding effects of unbalanced covariables.Results: The optimal cut-off value of the SII in the training cohort was 686, which was confirmed using the validation cohort. Multivariate analysis showed that both before and after PSM, SII values > 686 were independently associated with worse progression-free survival (PFS) ratio in both cohorts (before PSM, P = 0.008 and P = 0.008; after PSM, P = 0.008 and P = 0.007, respectively). Based on the analysis of independent prognostic factors of SII and N stage, we developed a categorical risk stratification model, which achieved significant discrimination among risk indexes associated with PFS and distant metastasis-free survival (DMFS) in the training cohort. There was no significant difference in PFS between RT alone and combined therapies within the low-and intermediate-risk groups (5-year PFS, 77.5% vs. 75.3%, P = 0.275). Patients in the high-risk group who received concurrent chemoradiotherapy experienced superior PFS compared with those who received other therapies (5-year PFS, 64.9% vs. 40.3%, P = 0.003).Conclusion: Pretreatment SII predicts PFS of patients with non-metastatic NPC. Prognostic risk stratification incorporating SII is instructive for selecting individualized treatment.

Purpose Treatment of multiple brain metastases with single-isocenter volumetric modulated arc therapy causes unnecessary exposure to normal brain tissue. In this study, a longitudinal grouping method was developed to reduce such unnecessary exposure. Materials and Methods This method has two main aspects: grouping brain lesions longitudinally according to their longitudinal projection positions in beam’s eye view, and rotating the collimator to 90° to make the multiple leaf collimator leaves conform to the targets longitudinally group by group. For 11 patients with multiple (5–30) brain metastases, two single-isocenter volumetric modulated arc therapy plans were generated using a longitudinal grouping strategy (LGS) and the conventional strategy (CVS). The prescription dose was 52 Gy for 13 fractions. Dose normalization to 100% of the prescription dose in 95% of the planning target volume was adopted. For plan quality comparison, Paddick conformity and the gradient index of the planning target volume, and the mean dose, the V 100% , V 50% , V 25% , and V 10% volumes of normal brain tissue were calculated. Results There were no significant differences between the LGS and CVS plans in Paddick conformity (p = 0.374) and the gradient index (p = 0.182) of the combined planning target volumes or for V 100% (p = 0.266) and V 50% (p = 0.155) of the normal brain. However, the V 25% and V 10% of the normal brain which represented the low-dose region were significantly reduced in the LGS plans (p = 0.004 and p = 0.003, respectively). Consistently, the mean dose of the entire normal brain was 12.04 and 11.17 Gy in the CVS and LGS plans, respectively, a significant reduction in the LGS plans (p = 0.003). Conclusions The longitudinal grouping method can decrease unnecessary exposure and reduces the low-dose range in normal brain tissue.

Objective:To evaluate the psychological pain of patients with head and neck cancer aged ≥60 years old before and after intensity-modulated radiotherapy (IMRT).Methods:Distress Thermometer (DT)(Chinese version) was used to investigate the degree and problems of psychological pain before and after IMRT for 85 elderly patients with head and neck cancer. The results before and after IMRT were compared by paired t-test. Relevant factors were identified by Logistic regression analysis. Results:The median age in the cohort was 66 years old (60-85 years old). The incidence rates of psychological pain were 73% and 87% before and after IMRT ( P<0.001). The corresponding incidence rates of severe distress were 6% and 34%( P<0.001). The main distress problems before IMRT were memory loss/attention deficit, worry, oral pain, economic problems, stress, sleep problems, and dry nose. The significantly-increased distress problems after IMRT were oral pain, constipation, eating, nausea, and dry nose. Logistic regression analysis showed gender ( OR=5.520, 95% CI 1.437-21.212, P=0.013), pre-treatment PG-SGA score ( OR=1.220, 95% CI 1.048-1.421, P=0.010) and medical insurance ( OR=0.230, 95% CI 0.053-0.995, P=0.049) were the relevant factors of the severe psychological distress before IMRT. Occupation ( OR=2.286, 95% CI 1.291-4.050, P=0.005) and medical insurance ( OR=0.089, 95% CI 0.029-0.276, P<0.001) were the relevant factors of severe psychological distress after IMRT. Conclusion:The incidence rate of distress is high in elderly patients with head and neck cancer before IMRT, which can be aggravated after IMRT, primarily the treatment-related physical pain problems.

PurposeThe high intracranial efficacy of targeted therapeutic agents poses a challenge in determining the optimal sequence of local radiation therapy (RT) and systemic treatment with tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) patients with brain metastasis (BM). Therefore, we conducted a cohort study to elucidate the appropriate treatment strategy, either upfront RT or deferred RT including a toxicity assessment, in these patients.Patients and MethodsWe retrospectively evaluated patients with gene-driven BMs from a single institution and divided them into deferred and upfront RT groups. Survival was estimated using a log-rank test. Intracranial progression was estimated using Fine-Gray competing risks model. Cox proportional hazards regression was performed for multivariable analysis in the entire group and subgroups.ResultsAmong the 198 eligible patients, 94 and 104 patients received deferred and upfront RT, respectively. The upfront RT group showed a lower intracranial progression risk with an adjusted sub-distribution hazard ratios of 0.41 (95% CI, 0.30–0.57) than did the deferred RT group (median intracranial progression-free survival [iPFS], 19.9 months vs. 11.1 months; p < 0.001). The median overall survival (OS; 43.2 months vs. 49.1 months, p = 0.377) and BM-specific survival (92.1 months vs. 82.9 months, p = 0.810) after salvage therapy were not significantly different between the upfront and deferred groups. Among patients with progressed extracranial disease, the deferred RT group showed significantly better OS than did the upfront RT group (44.0 vs. 28.1 months, p = 0.022). Grade 3–4 treatment-related adverse events were rare, and similar toxicities were observed between the two groups.ConclusionCompared to the deferred RT group, the upfront RT group achieved longer iPFS and similar survival outcomes in most patients with gene-driven NSCLC BM, although patients with progression of extracranial disease might benefit from deferred RT. Both groups showed well-tolerated toxicities.Trial registration IDNCT04832672.

Abstract Purpose Conditional survival (CS) and failure hazard estimations can provide important dynamic prognostic information for clinical decision‐making and surveillance counseling. The current study aimed to investigate the CS and dynamic failure hazard in non‐metastatic nasopharyngeal carcinoma (NPC) treated with intensity‐modulated radiotherapy (IMRT). Methods Conditional overall survival (COS) and progression‐free survival (CPFS) estimates adjusted for age and gender against each AJCC 8th stage were calculated. Multivariable Cox regression (MCR) models were fitted in the entire population at baseline and subsequently separate MCR models were fitted in patients who have maintained event‐free time of 1 to 10 years to generate respective hazard ratio (HR). Annual hazard rates of death and progression over 10 years for each stage were also estimated. Results A total of 1993 patients were eligible for analysis. The estimated 5‐year OS and PFS for entire cohort were 79.0% and 70.7% at initial diagnosis. After 5 years of event‐free follow‐up, additional 5‐year COS and CPFS increased to 85.9% and 85.5%, respectively. Stage I/II maintained dramatically favorable CS and low hazard (< 5%) of death and progression over time. Relative to stage I/II, stage III manifested non‐significantly higher failure hazard for the first 3 years of survivorship and approached to similar level of stage I/II afterwards. Stage IVA presented most impressive improvement in terms of both COS (∆=9.8%) and CPFS (∆ = 16.8%) whereas still drastically inferior to that of stage I‐III across all conditional time points. After 4 years of follow‐up, progression hazard of stage IVA became relatively steady of approximate 6%. Conclusions Survival prospect of non‐metastatic NPC improves over years with distinct dynamic patterns across stages, providing important implications for personalized decision‐making in terms of both clinical management and surveillance counseling. Stage‐dependent and hazard‐adapted clinical management and surveillance are warranted.

Our team utilized qRT-PCR for prospecting miR-32 expression level in primary lung carcinoma tissues and cell lines, as well as Kaplan–Meier method for dissecting the relation of miR-32 expression with the prognosis of lung carcinoma. We transfected lung cancer A549 cells with miR-32 mimic/inhibitor and mimic/inhibitor NC, and appraised the influences of miR-32 on the phenotype changes of lung carcinoma cells via MTT assay, wound healing assay and cell apoptosis assay, separately. Then the target gene of miR-32 was predicted via bioinformatics. Finally, Western blotting was adopted for analyzing the impact of alteration of miR-32 expression on the PI3K/Akt axis in A549 cells. In lung carcinoma tissues as well as cells, miR-32 expression is down-regulated, and miR-32 partakes in the progress of lung carcinoma via PI3K/Akt pathway.