The impact of submandibular glands protection on xerostomia as monitored by diffusion-weighted imaging in nasopharyngeal carcinoma patients.

PURPOSE: To determine the impact of sparing submandibular glands (SMGs) on alleviating xerostomia and the functional dynamics of the irradiated parotid glands (PGs) and sublingual glands (SLGs) by diffusion-weighted imaging. METHODS: 97 participants underwent 9 rounds of DWI scans before IC (pre-IC), pre-radiation (pre-RT), the midpoint of radiation (mid-RT), the end of radiation (post-RT), 1, 3, 6, 9, 12 (12m-RT) months following radiation. Apparent diffusion coefficient of SMGs (ADCSMG), PGs (ADCPG), and SLGs (ADCSLG), xerostomia questionnaire scores (XQ), and saliva flow rate measures under unstimulated (uSFR) and stimulated condition (sSFR) were documented. RESULTS: ADCPG, ADCSMG, ADCSLG, and XQ showed a rapid increase with a top at 3m-RT followed by regression, whereas uSFR and sSFR had the reverse trend. The change rate of ADC correlated with the dose to PGs, SMGs, and SLGs, as well as uSFR, sSFR, and XQ scores (p < 0.05 for all, except for uSFR with ADCPG (p = 0.063)). Maingroup for ADCPG, uSFR, and sSFR were significant (p values were 0.028, 0.000, 0.000 respectively); ADCPG in SMG sparing group was lower while uSFR, and sSFR were higher than those in the SMG-unsparing group. Simplegroup for ADCSMG, ADCSLG (all p < 0.05 from mid-RT to 12m-RT), and XQ (all p < 0.001 at mid-, 6m-, 9m-, and 12m-RT) were significant; ADCSMG, ADCSLG, and XQ were lower in the SMG-sparing group. CONCLUSIONS: SMG protection has a great impact on the functional retention of PGs and SLGs, resulting in alleviating xerostomia and improving quality of life. TRIAL REGISTRATION: The clinical trial was also registered with the Chinese Clinical Study Registry (registered number: ChiCTR1900024328, Date: July 6, 2019; URL: https://www.chictr.org.cn/showproj.aspx?proj=40726 ).

[Automatic segmentation of head and neck organs at risk based on three-dimensional U-NET deep convolutional neural network].

The segmentation of organs at risk is an important part of radiotherapy. The current method of manual segmentation depends on the knowledge and experience of physicians, which is very time-consuming and difficult to ensure the accuracy, consistency and repeatability. Therefore, a deep convolutional neural network (DCNN) is proposed for the automatic and accurate segmentation of head and neck organs at risk. The data of 496 patients with nasopharyngeal carcinoma were reviewed. Among them, 376 cases were randomly selected for training set, 60 cases for validation set and 60 cases for test set. Using the three-dimensional (3D) U-NET DCNN, combined with two loss functions of Dice Loss and Generalized Dice Loss, the automatic segmentation neural network model for the head and neck organs at risk was trained. The evaluation parameters are Dice similarity coefficient and Jaccard distance. The average Dice Similarity coefficient of the 19 organs at risk was 0.91, and the Jaccard distance was 0.15. The results demonstrate that 3D U-NET DCNN combined with Dice Loss function can be better applied to automatic segmentation of head and neck organs at risk.

Comparison of three-dimensional conformal radiation therapy, intensity-modulated radiation therapy, and volumetric-modulated arc therapy in the treatment of cervical esophageal carcinoma.

The aim of this study was to evaluate the effectiveness and toxicities of three-dimensional conformal radiation therapy (3DCRT), intensity-modulated radiation therapy (IMRT), and volumetric-modulated arc therapy (VMAT) in patients with cervical esophageal cancer. Specifically, we asked whether technological advances conferred an advantage with respect to the clinical curative effect. Seventy-eight patients with cervical esophageal cancer treated with definitive radiotherapy with or without concomitant chemotherapy at our institution between 2007 and 2014 were enrolled in the study: 26 received 3DCRT, 30 were treated with IMRT, and 22 underwent VMAT. Kaplan-Meier analysis and the Cox proportional hazard model were used to analyze overall survival (OS) and failure-free survival (FFS). Treatment-related toxicity was also assessed. For all patients, the 2-year OS and FFS rates were 56.2 and 53.9%, respectively. The 2-year OS for the 3DCRT, IMRT, and VMAT groups was 53.6, 55.6, and 60.6%, respectively (P = 0.965). The corresponding 2-year FFS rates were 49.5, 56.7, and 60.1% (P = 0.998). A univariate analysis of the complete response to treatment showed an advantage of treatment modality with respect to OS (P < 0.001). The development of acute hematologic toxicity was not significantly different among the three groups. The survival rates of patients treated with IMRT and VMAT were comparable to the survival of patients administered 3DCRT, while lower lung mean dose, V20, maximum dose of brachial plexus and spinal cord. Grade 1 radiation pneumonitis occurred significantly less in patients treated with IMRT and VMAT than with 3DCRT (P = 0.011). A complete response was the most important prognostic factor of the patients with cervical esophageal cancer.

Dose Evaluation of Fractionated Schema and Distance From Tumor to Spinal Cord for Spinal SBRT with Simultaneous Integrated Boost: A Preliminary Study.

BACKGROUND This study investigated and quantified the dosimetric impact of the distance from the tumor to the spinal cord and fractionation schemes for patients who received stereotactic body radiation therapy (SBRT) and hypofractionated simultaneous integrated boost (HF-SIB). MATERIAL AND METHODS Six modified planning target volumes (PTVs) for 5 patients with spinal metastases were created by artificial uniform extension in the region of PTV adjacent spinal cord with a specified minimum tumor to cord distance (0-5 mm). The prescription dose (biologic equivalent dose, BED) was 70 Gy in different fractionation schemes (1, 3, 5, and 10 fractions). For PTV V100, Dmin, D98, D95, and D1, spinal cord dose, conformity index (CI), V30 were measured and compared. RESULTS PTV-to-cord distance influenced PTV V100, Dmin, D98, and D95, and fractionation schemes influenced Dmin and D98, with a significant difference. Distances of ≥2 mm, ≥1 mm, ≥1 mm, and ≥0 mm from PTV to spinal cord meet dose requirements in 1, 3, 5, and 10 fractionations, respectively. Spinal cord dose, CI, and V30 were not impacted by PTV-to-cord distance and fractionation schemes. CONCLUSIONS Target volume coverage, Dmin, D98, and D95 were directly correlated with distance from the spinal cord for spine SBRT and HF-SIB. Based on our study, ≥2 mm, ≥1 mm, ≥1 mm, and ≥0 mm distance from PTV to spinal cord meets dose requirements in 1, 3, 5 and 10 fractionations, respectively.

Clinical analysis of intracranial germinoma's craniospinal irradiation using helical tomotherapy.

OBJECTIVE: To evaluate the short-term clinical outcomes of intracranial germinoma patients treated with craniospinal irradiation (CSI) using helical tomotherapy (HT) system in our center. METHODS: Twenty-three patients who were treated with CSI in our center from January 2008 to July 2012 were collected, with an average age of 20. All of the patients' CSI used the HT system. The total doses were 27-36 Gy/15-20 F (1.5-2 Gy per fraction), and total local doses were 46-60 Gy/30-50 F (5 fractions per week). All female patients for CSI were treated with left-right parallel-opposed field irradiation to protect their ovarian functions. Median follow-up time was 30.9 months (range, 5-67 months). The SPSS19.0 software was used, and the overall survival (OS) was calculated using the Kaplan-Meier method. RESULTS: Among 17 patients with assessable tumors, 9 cases (52.9%) were CR, 7 cases (41.2%) were PR, and 1 case (5.9%) was SD. Hematological toxicity was the severest side-effect occurred in the procedure of CSI. The level 1-4 acute leukopenia were 8.7%, 30.4%, 34.8% and 21.7% and the level 1-4 acute thrombopenia were 8.7%, 30.4%, 21.7% and 8.7%, respectively. CONCLUSIONS: For primary intracranial germinomas, HT can be used to implement CSI for simplifying radiotherapy procedures, improving radiotherapy accuracy, enhancing protection of peripheral organs at risk (ORA) and guaranteeing therapeutic effects. With the acceptable acute and long-term toxicity, CSI using HT in intracranial germinoma patients can be a safe and alternative mode.

[Effect of adaptive replanning on adverse reactions and clinical outcome in nasopharyngeal carcinoma treated by helical tomotherapy].

OBJECTIVE: To observe the effect of adaptive replanning on adverse reactions and clinical outcome of nasopharyngeal carcinoma treated by helical tomotherapy. METHODS: Fifty nasopharyngeal carcinoma patients treated by TomoTherapy system were retrospectively analyzed. Among these patients, 25 received repetitive CT simulation and replanning, and another 25 case-matched control patients without replanning were identified by matching age, gender, pathological type, UICC stage, weight loss, etc. Wilcoxon test was used to evaluate the effect of replanning on acute and chronic radiation reactions within individuals. Kaplan-Meier study was used to estimate the survival of patients with or without replanning. RESULTS: There was a significant difference in late salivary grand damage between the replanning and the control group (P=0.046), while no difference was observed in acute or other late side effects between the two groups. The median follow-up of the two groups was 32 months (7-42 months) and 26 months (8-46 months), respectively. The median local relapse-free survival time, 2-year local relapse-free survival and 2-year lymphnode relapse-free survival in the two groups were similar (36 months, 92% and 100%). No significant difference was found in the 2-year metastasis relapsefree survival (80% and 96%) and the 2-year overall survival between the two groups (88% and 92%, P>0.05). CONCLUSION: Adaptive replanning may reduce the severity of late damage of salivary glands after helical tomotherapy in nasopharyngeal carcinoma patients without improvement of 2-year survival rate.

Evaluation of Dose Calculation Based on Cone-Beam CT Using Different Measuring Correction Methods for Head and Neck Cancer Patients.

Purpose: To investigate and compare 2 cone-beam computed tomography (CBCT) correction methods for CBCT-based dose calculation. Materials and Methods: Routine CBCT image sets of 12 head and neck cancer patients who received volumetric modulated arc therapy (VMAT) treatment were retrospectively analyzed. The CBCT images obtained using an on-board imager (OBI) at the first treatment fraction were firstly deformable registered and padded with the kVCT images to provide enough anatomical information about the tissues for dose calculation. Then, 2 CBCT correction methods were developed and applied to correct CBCT Hounsfield unit (HU) values. One method (HD method) is based on protocol-specific CBCT HU to physical density (HD) curve, and the other method (HM method) is based on histogram matching (HM) of HU value. The corrected CBCT images (CBCTHD and CBCTHM for HD and HM methods) were imported into the original planning system for dose calculation based on the HD curve of kVCT (the planning CT). The dose computation result was analyzed and discussed to compare these 2 CBCT-correction methods. Results: Dosimetric parameters, such as the Dmean, Dmax and D5% of the target volume in CBCT plan doses, were higher than those in the kVCT plan doses; however, the deviations were less than 2%. The D2%, in parallel organs such as the parotid glands, the deviations from the CBCTHM plan dose were less than those of the CBCTHD plan dose. The differences were statistically significant (P < .05). Meanwhile, the V30 value based on the HM method was better than that based on the HD method in the oral cavity region (P = .016). In addition, we also compared the γ passing rates of kVCT plan doses with the 2 CBCT plan doses, and negligible differences were found. Conclusion: The HM method was more suitable for head and neck cancer patients than the HD one. Furthermore, with the CBCTHM-based method, the dose calculation result better matches the kVCT-based dose calculation.

Development and validation of a nomogram for prediction of recovery from moderate-severe xerostomia post-radiotherapy in nasopharyngeal carcinoma patients.

PURPOSE: Aim to create and validate a comprehensive nomogram capable of accurately predicting the transition from moderate-severe to normal-mild xerostomia post-radiotherapy (postRT) in patients with nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: We constructed and internally verified a prediction model using a primary cohort comprising 223 patients who were pathologically diagnosed with NPC from February 2016 to December 2019. LASSO regression model was used to identify the clinical factors and relevant variables (the pre-radiotherapy (XQ-preRT) and immediate post-radiotherapy (XQ-postRT) xerostomia questionnaire scores, as well as the mean dose (Dmean) delivered to the parotid gland (PG), submandibular gland (SMG), sublingual gland (SLG), tubarial gland (TG), and oral cavity). Cox proportional hazards regression analysis was performed to develop the prediction model, which was presented as a nomogram. The models' performance with regard to calibration, discrimination, and clinical usefulness was evaluated. The external validation cohort comprised 78 patients. RESULTS: Due to better discrimination and calibration in the training cohort, age, gender, XQ-postRT, and Dmean of PG, SMG, and TG were included in the individualized prediction model (C-index of 0.741 (95% CI:0.717 to 0.765). Verification of the nomogram's performance in internal and external validation cohorts revealed good discrimination (C-index of 0.729 (0.692 to 0.766) and 0.736 (0.702 to 0.770), respectively) and calibration. Decision curve analysis revealed that the nomogram was clinically useful. The 12-month and 24-month moderate-severe xerostomia rate was statistically lower in the SMG-spared arm (28.4% (0.230 to 35.2) and 5.2% (0.029 to 0.093), respectively) than that in SMG-unspared arm (56.8% (0.474 to 0.672) and 12.5% (0.070 to 0.223), respectively), with an HR of 1.84 (95%CI: 1.412 to 2.397, p = 0.000). The difference in restricted mean survival time for remaining moderate-severe xerostomia between the two arms at 24 months was 5.757 months (95% CI, 3.863 to 7.651; p = 0.000). CONCLUSION: The developed nomogram, incorporating age, gender, XQ-postRT, and Dmean to PG, SMG, and TG, can be used for predicting recovery from moderate-severe xerostomia post-radiotherapy in NPC patients. Sparing SMG is highly important for the patient's recovery.

Long-term outcomes of nasopharyngeal carcinoma treated with helical tomotherapy using simultaneous integrated boost technique: A 10-year result.

Background: To evaluate the long-term survival and treatment-related toxicities of helical tomotherapy (HT) in nasopharyngeal carcinoma (NPC) patients. Methods: One hundred and ninety newly diagnosed non-metastatic NPC patients treated with HT from September 2007 to August 2012 were analyzed retrospectively. The dose at D95 prescribed was 70-74Gy, 60-62.7Gy and 52-56Gy delivered in 33 fractions to the primary gross tumor volume (pGTVnx) and positive lymph nodes (pGTVnd), the high risk planning target volume (PTV1), and the low risk planning target volume (PTV2), respectively, using simultaneous integrated boost technique. The statistical analyses were performed and late toxicities were evaluated and scored according to the Common Terminology Criteria for Adverse Events (version 3.0). Results: The median follow-up time was 145 months. The 10-year local relapse-free survival (LRFS), nodal relapse-free survival (NRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were 94%, 95%, 86%, and 77.8%; respectively. Fifty (26.3%) patients had treatment-related failures at the last follow-up visit. Distant metastasis, occurred in 25 patients, was the major failure pattern. Multivariate analysis showed that age and T stage were independent predictors of DMFS and OS, Concomitant chemotherapy improved overall survival, but anti-EGFR monoclonal antibody therapy failed. The most common late toxicities were mainly graded as 1 or 2. Conclusions: Helical tomotherapy with simultaneous integrated boost technique offered excellent long-term outcomes for NPC patients, with mild late treatment-related toxicities. Age and clinical stage were independent predictors of DMFS and OS. And, concurrent chemotherapy means better OS. Further prospective study is needed to confirm the superiority of this technology and to evaluate the roles of anti-EGFR monoclonal antibody treatment.

Moderate hypofractionated helical tomotherapy for older patients with localized prostate cancer: long-term outcomes of a phase I-II trial.

BACKGROUND: Our previous study showed that two different regimens of moderate hypofractionated radiotherapy (HFRT) delivered with helical tomotherapy (HT) are well tolerated in older prostate cancer patients. We provide a longterm efficacy and toxicity after > 7 years of follow-up. PATIENTS AND METHODS: The study recruited 33 patients from February 2009 to July 2011 (76 Gy/34F; Group-1); and 34 from July 2011 to February 2014 (71.6 Gy/28F; 50.4 Gy/25F for the risk of pelvic lymph nodes involvement (LNI) >15%; Group-2). The primary outcomes were biochemical failure (BF), biochemical failure and clinical disease failure (BCDF), progression-free survival (PFS), overall survival (OS), late genitourinary (GU) and gastrointestinal (GI) toxicity. RESULTS: The average ages of two groups were 80 and 77 years and the proportions of patients with LNI > 15% were 69.7% and 73.5%, respectively. At the final follow-up in February 2020, 27.3% and 20.6% cases experienced BF, with a median time until BF of 3.3 years. A total of 38.8% patients reached primary endpoints, in which 18 deaths were reported BCDF events (45.5% vs. 32.4%, p = 0.271). There was no significant difference in 7-year PFS (68.6% vs. 74.8%, p = 0.591), BCDF (45.5% vs. 32.4%, p = 0.271) and OS (71.9% vs. 87.5%, p = 0.376) for full set analysis and for subgroup analysis (all p > 0.05). The incidence of grade ≥ 2 late GU (6.2% vs. 6.3%, p = 0.127) and GI toxicities (9.4% vs. 15.6%, p = 0.554) was comparable. CONCLUSIONS: In older patients with localized prostate cancer, two moderate hypofractionated regimens were all well tolerated with similar, mild late toxicities and satisfactory survival, without necessity of prophylactic pelvic node irradiation.

The Acute Toxicities and Efficacy of Concurrent Chemotherapy With Docetaxel Plus Cisplatin, or Docetaxel, or Cisplatin and Helical Tomotherapy in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma: A Randomized Single-Center Phase II Trial.

Objective: The objective of this trial is to evaluate and compare the acute toxicity in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) treated with docetaxel plus cisplatin, or docetaxel, or cisplatin concurrently with helical tomotherapy during concurrent chemoradiotherapy (CCRT). Methods: In a prospective, single-center, open-label, randomized phase II study, after 2 cycles of induction chemotherapy with docetaxel plus cisplatin regimen, 125 patients with LA-NPC (stage III and IVA, UICC eighth) diagnosed pathologically from June 2017 to November 2019 were randomized into CCRT with docetaxel plus cisplatin group (25 patients), CCRT with docetaxel group (50 patients), and CCRT with cisplatin group (50 patients). The incidence of grade 3 or 4 acute toxicities and clinical efficacy were analyzed among the 3 groups. Results: Safety evaluation was completed in all the 125 patients, during the CCRT period, 66.4% of patients completed 3 cycles of chemotherapy, 24.0% completed 2 cycles of chemotherapy, and 9.6% completed 1 cycle of chemotherapy according to the research plan. The incidence of grade 3 or 4 acute toxicity in CCRT with docetaxel plus cisplatin (DP), docetaxel (D), and cisplatin (P) groups was 88.0%, 72.0%, and 56.0%, respectively. The incidence of grade 3 or 4 acute toxicities in the DP group was significantly higher than that in the D and P groups (P = .015), no significant difference was detected between the D and P groups (P = .096). The most common toxicities were mucositis (40.0%), leukopenia (29.6%), neutropenia (26.4%), and pharyngo-esophagitis (12.0%); compared to D and P groups, DP group did not significantly improved the 3-year overall survival (96.0% vs 87.0% and 87.6%), progression-free survival (92.0% vs 79.7% and,76.9%), locoregional failure-free survival (96.0% vs 91.8% and 92.7%), and distant failure-free survival (100% vs 90.0% and 89.0%), there were no significant difference in survival data among the 3 groups (all P > .05). Conclusions: Higher survival benefits did not achieve from intensified CCRT with DP, CCRT with P or D obtained similar short-term survival outcomes with similar acceptable toxicities in LA-NPC patients.

Efficacy and safety of combined treatment with pembrolizumab in patients with locally advanced or metastatic esophageal squamous cell carcinoma in the real world.

Background: Treatments for patients with advanced esophageal cancer are still limited. Pembrolizumab has demonstrated antitumor activity in patients with advanced esophageal cancer in previous studies. Few studies have assessed safety and efficacy in routine clinical practice. We investigated the real-world outcomes of pembrolizumab for patients with advanced esophageal cancer. Methods: This retrospective, observational study collected 57 advanced esophageal squamous cell carcinoma (ESCC) patients from October 1, 2019 to October 1, 2021, 57 who received different patterns of treatments according to the staging were collected. Briefly, patients diagnosed with locally advanced and surgically resectable ESCC received neoadjuvant therapy followed by surgery. For patients with locally advanced, unresectable ESCC, the treatment regimen including chemoradiotherapy combined with pembrolizumab was performed. Patients with metastatic ESCC or those not suitable for radiotherapy received pembrolizumab plus chemotherapy. Safety was assessed in all treated patients. The objective response rate (ORR) was used to evaluate the efficacy. Results: The ORR was 74.1% (40/54) among all patients. The most common adverse events (AEs) were leukopenia (36.8%, 21/57), nausea (28.1%, 16/57), and thrombocytopenia (14%, 8/57). Grade III and higher AEs were observed in 9 of the 57 patients (15.8%). Conclusions: For patients with advanced ESCC, combined treatment with pembrolizumab was effective and safe. Multicenter studies should be carried out for further confirmation.

A comparative study of functional MRI in predicting response of regional nodes to induction chemotherapy in patients with nasopharyngeal carcinoma.

Purpose: To identify and compare the value of functional MRI (fMRI) in predicting the early response of metastatic cervical lymph nodes (LNs) to induction chemotherapy (IC) in nasopharyngeal carcinoma (NPC) patients. Methods: This prospective study collected 94 metastatic LNs from 40 consecutive NPC patients treated with IC from January 2021 to May 2021. Conventional diffusion-weighted imaging, diffusion kurtosis imaging, intravoxel incoherent motion, and dynamic contrast-enhanced magnetic resonance imaging were performed before and after IC. The parameter maps apparent diffusion coefficient (ADC), mean diffusion coefficient (MD), mean kurtosis (MK), Dslow, Dfast, perfusion fraction (PF), Ktrans, Ve, and Kep) of the metastatic nodes were calculated by the Functool postprocessing software. All LNs were classified as the responding group (RG) and non-responding group (NRG) according to Response Evaluation Criteria in Solid Tumors 1.1. The fMRI parameters were compared before and after IC and between the RG and the NRG. The significant parameters are fitted by logistic regression analysis to produce new predictive factor (PRE)-predicted probabilities. Logistic regression analysis and receiver operating characteristic (ROC) curves were performed to further identify and compare the efficacy of the parameters. Results: After IC, the mean values of ADC, MD, and Dslow significantly increased, while MK, Dfast, and Ktrans values decreased dramatically, while no significant difference was detected in Ve and Kep. Compared with NRG, PF-pre and Ktrans-pre values in the RG were higher statistically. The areas under the ROC for the pretreatment PF, Ktrans, and PRE were 0.736, 0.722, and 0.810, respectively, with the optimal cutoff value of 222 × 10-4, 934 × 10-3/min, and 0.6624, respectively. Conclusions: The pretreatment fMRI parameters PF and Ktrans showed promising potential in predicting the response of the metastatic LNs to IC in NPC patients. Clinical Trial Registration: This study was approved by the ethics board of the Chinese PLA General Hospital, and registered on 30 January 2021, in the Chinese Clinical Trial Registry; http://www.chictr.org.cn/showproj.aspx?proj=121198, identifier (ChiCTR2100042863).

Induction Chemotherapy Plus Simultaneous Modulated Accelerated Radiation Therapy in Non-operative Hypopharyngeal and Supraglottic Laryngeal Squamous Cell Carcinoma: Long-Term Outcome of a Prospective Phase 2 Study.

Background: To evaluate the toxicities and long-term outcomes of induction chemotherapy (ICT) plus simultaneous modulated accelerated radiation therapy (SMART) in non-operative hypopharyngeal and supraglottic laryngeal squamous cell carcinoma (SCCH/L). Materials and Methods: This was a prospective phase 2 study. Patients diagnosed with SCCH/L, aged from 18 to 75, staged from III to IVB in accordance with the AJCC 2010 criteria, and refusing surgery were eligible. The patients were treated with 2-3 cycles of docetaxel-cisplatin-based ICT and SMART combined with 2-3 cycles of cisplatin-based concurrent chemotherapy. The prescription dose to the primary tumor and metastatic nodes was 69 Gy in 30 fractions. Acute and late toxicities were assessed according to the established Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) criteria, and long-term outcomes were analyzed. Results: Between February 2013 and June 2015, 55 newly diagnosed SCCH/L patients were enrolled. No grade 2 or worse acute xerostomia was noted. The incidences of grade 3 acute dermatitis, oral mucositis, and pharyngoesophagitis were 12.7, 3.6, and 12.7%, respectively. The median follow-up time was 48 months (range 5.5-74 months). The main late toxicity was hoarseness or sore throat, with an incidence of 32.7%. The 5-year functional larynx-preservation survival was 51.5%. The 3- and 5-year locoregional control and overall survival were 58.2, 51.5, 63.6, and 54.1%, respectively. Conclusions: The ICT plus SMART with a regimen of 69 Gy/30 F for the treatment of SCCH/L demonstrated acceptable severe toxicity, satisfactory long-term outcomes, and laryngeal function preservation.

Induction chemotherapy with albumin-bound paclitaxel plus lobaplatin followed by concurrent radiochemotherapy for locally advanced esophageal cancer.

BACKGROUND: Albumin-bound paclitaxel (ABP) has been used as second- and higher-line treatments for advanced esophageal cancer, and its efficacy and safety have been well demonstrated. Lobaplatin (LBP) is a third-generation platinum antitumor agent; compared with the first two generations of platinum agents, it has lower toxicity and has been approved for the treatment of breast cancer, small cell lung cancer, and chronic granulocytic leukemia. However, its role in the treatment of esophageal cancer warrants further investigations. AIM: To investigate the efficacy and safety of induction chemotherapy with ABP plus LBP followed by concurrent radiochemotherapy (RCT) for locally advanced esophageal cancer. METHODS: Patients with pathologically confirmed advanced esophageal squamous cell carcinoma (ESCC) at our hospital were enrolled in this study. All patients were treated with two cycles of induction chemotherapy with ABP plus LBP followed by concurrent RCT: ABP 250 mg/m2, ivgtt, 30 min, d1, every 3 wk; and LBP, 30 mg/m2, ivgtt, 2 h, d1, every 3 wk. A total of four cycles were scheduled. The dose of the concurrent radiotherapy was 56-60 Gy/28-30 fractions, 1.8-2.0 Gy/fraction, and 5 fractions/wk. RESULTS: A total of 29 patients were included, and 26 of them completed the treatment protocol. After the induction chemotherapy, the objective response rate (ORR) was 61.54%, the disease control rate (DCR) was 88.46%, and the progressive disease (PD) rate was 11.54%; after the concurrent RCT, the ORR was 76.92%, the DCR was 88.46%, and the PD rate was 11.54%. The median progression-free survival was 11.1 mo and the median overall survival was 15.83 mo. Cox multivariate analysis revealed that two cycles of induction chemotherapy followed by concurrent RCT significantly reduced the risk of PD compared with two cycles of chemotherapy alone (P = 0.0024). Non-hematologic toxicities were tolerable, and the only grade 3 non-hematologic toxicity was radiation-induced esophagitis (13.79%). The main hematologic toxicity was neutropenia, and no grade 4 adverse event occurred. CONCLUSION: Induction chemotherapy with ABP plus LBP followed by concurrent RCT is effective in patients with locally advanced ESCC, with mild adverse effects. Thus, this protocol is worthy of clinical promotion and application.

Case Report: Sequential Combination Targeted Therapy With Type I and II MET Inhibitors in a Metastatic EGFR-Mutated, MET-Amplified NSCLC Patient With Acquired MET Y1230H Mutation.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the standard of care for advanced non-small-cell lung cancer (NSCLC) patients. However, most patients will eventually develop resistance. For EGFR-TKI resistance mediated by MET amplification, the combination of EGFR and MET TKIs has shown promising results in early clinical trials. However, acquired resistance to MET inhibitors forms a formidable challenge to this dual blockade approach. Here, we presented an NSCLC patient with EGFR exon 19 deletion (ex19del) who was resistant to first-line erlotinib treatment but responded to chemotherapy. Given the finding of MET overexpression/amplification after disease progression, the patient received gefitinib plus crizotinib with a partial response. Her disease progressed again, and molecular testing revealed a novel MET Y1230H mutation and a PD-L1 TPS score of 75%. She received a salvage regime consisting of gefitinib, cabozantinib, and pembrolizumab with a partial response. Since we now know that EGFR ex19del NSCLC patients generally do not respond to PD-1 blockade therapy, this response is more likely the contribution from gefitinib plus cabozantinib. Therefore, sequential use of type I and II MET inhibitors in EGFR/MET dual blockade may be an effective therapeutic option for EGFR-mutant, MET-amplified NSCLC.

Changes in the nutritional status of nine vitamins in patients with esophageal cancer during chemotherapy.

BACKGROUND: Many studies have investigated the relationships between vitamins and esophageal cancer (EC). Most of these studies focused on the roles of vitamins in the prevention and treatment of EC, and few studies have examined the changes in vitamin nutritional status and their influencing factors before and after chemotherapy for EC. Chemotherapy may have a considerable effect on EC patients' vitamin levels and hematological indicators. AIM: To research the nutritional status of multiple vitamins in EC patients during chemotherapy and to assess its clinical significance. METHODS: EC patients admitted to our center from July 2017 to September 2020 were enrolled in this study. Serum concentrations of nine vitamins (A, D, E, B9, B12, B1, C, B2 and B6), hemoglobin, total protein, albumin, blood calcium, blood phosphorus concentrations and body mass index (BMI) were measured in all EC patients. The changes in nine vitamins, hematological indicators and BMI were compared before and after two cycles of chemotherapy. The possible influential factors were analyzed. RESULTS: In total, 203 EC patients receiving chemotherapy were enrolled in this study. Varying degrees of vitamin A, D, C and B2 deficiency and weight loss were found in these patients, and the proportions of vitamin B2 and vitamin C deficiencies increased significantly after chemotherapy (both P < 0.05). Serum concentrations of vitamins A, C, B2 and B6 and BMI before and after chemotherapy were statistically significant (all P < 0.05). Multivariate analysis showed that vitamin A levels significantly differed between male and female EC patients, whereas vitamin D concentration significantly differed in EC patients in different stages (all P < 0.05). Correlations were observed between the changes in serum concentrations of vitamin A and C before and after two cycles chemotherapy and the change in BMI (P < 0.05). Hemoglobin, total protein, serum albumin and blood calcium concentrations significantly decreased in EC patients after chemotherapy (all P < 0.05), while the blood phosphorus level significantly increased after chemotherapy (P < 0.05). Using the difference in vitamin concentrations as the independent variables and the difference in BMI as the dependent variable, logistic regression analysis revealed statistically significant differences for vitamin A, vitamin D and vitamin C (F = 5.082, P = 0.002). CONCLUSION: Vitamin A, D, C and B2 were mainly deficient in patients with EC during chemotherapy. Multivitamin supplementation may help to improve the nutritional status, chemotherapy tolerance and efficacy.

Neoadjuvant chemoradiotherapy plus surgery in the treatment of potentially resectable thoracic esophageal squamous cell carcinoma.

BACKGROUND: In recent years, neoadjuvant chemoradiotherapy (NCRT) combined with surgery has been gradually applied in patients with locally advanced thoracic esophageal cancer, but its effectiveness and safety remains unclear. In this clinical trial, we prospectively investigated the efficacy and safety of NCRT plus surgery in the treatment of thoracic esophageal squamous cell carcinoma (TESCC). AIM: To investigate the efficacy and safety of NCRT combined with surgery in the treatment of potentially resectable TESCC. METHODS: Thirty patients with advanced TESCC hospitalized in our hospital from July 2016 to June 2019 were prospectively studied. All patients received NCRT, which included intensity modulated conformal radiotherapy (40-44 Gy/20-22f, 2 Gy/f) and chemotherapy (paclitaxel 150-175 mg/m2d1, 22 + lobaplatin 25-30 mg/m2d2, 23 for two cycles). Surgery was performed after radiotherapy and chemotherapy. The effectiveness and safety of these treatments were observed. RESULTS: Among these 30 patients, complete response was achieved in two cases (6.7%) and partial response in 26 cases (86.7%), yielding an objective response rate of 100%. All patients underwent radical surgery successfully. The R0 resection rate was 100%, and the pathologic complete response rate was 33.3%. The incidence of grade III- IV granulocytopenia was 10% during the NCRT, and anastomotic leakage occurred in one patient after surgery. CONCLUSION: For patients with potentially resectable TESCC, NCRT can effectively reduce the tumor size, increase R0 resection rate, and achieve obvious pathological degradation, with mild adverse reactions. Thus, it is worthy of wider clinical application.

Diagnosis and treatment of hemangiopericytoma in the central nervous system.

OBJECTIVE: This study aimed to explore the clinical characteristics and treatment of the hemangiopericytoma (HPC) in the central nervous system. MATERIALS AND METHODS: Clinical data from 14 patients with HPC in the central nervous system who were followed up for 12-107 months were retrospectively analyzed, and relevant literature was reviewed. RESULTS: All 14 patients underwent surgery and postoperative pathologic diagnosis, including 8 cases of total excision, 3 cases of subtotal excision, and 3 cases of partial excision. There were 7 recurrent cases (50%, 4 cases of total excision, 1 case of subtotal excision, and 2 cases of partial excision, none of them received postoperative radiotherapy) with a median relapse time of 39 months, where the median relapse time after total excision was 41.5 months, and after nontotal excision was 17 months. In addition, patients could survive for a long time after reoperation following relapse and after receiving postoperative radiotherapy. CONCLUSION: The diagnosis of HPC depends on the pathology. Currently, the surgery and postoperative radiotherapy provide a good treatment results, while the wholeness of surgical resection is of particular importance.

A clinical study of polyethylene glycol recombinant human granulocyte colony-stimulating factor prevention neutropenia syndrome in patients with esophageal carcinoma and lung cancer after concurrent chemoradiotherapy.

OBJECTIVE: To compare the efficacy and safety of PEG-rhG-CSF and recombinant human G-CSF (rhG-CSF) for the prevention and delayed application in febrile neutropenia, hospitalization rate in concurrent chemoradiotherapy of tumors. METHODS: A total of 163 patients, who received concurrent chemoradiotherapy for solid tumors. There were 75 patients in the PEG-rhG-CSF group (PEG group), who received 146 cycles of concurrent chemoradiotherapy, of which 132 cycles (90.42%) were prophylactic therapy, while 9 cycles (6.16%) were delayed therapy. There were 88 patients in the rhG-CSF group (rhG group), who received 164 cycles of concurrent chemoradiotherapy, of which 48 cycles (29.3%) were prophylactic, while 116 cycles (70.7%) were delayed therapy. G-CSF was used for prophylaxis in 180 cycles of chemotherapy, with delayed use in 130 cycles. RESULTS: Comparison between the prevention group and the delayed group showed that the incidence of neutropenia-related hospitalization was 4.44% and 14.62%, respectively (OR = 0.272, 95% CI, 0.115-0.642) (P = 0.002). Intravenous antibiotics usage was 2.78% vs. 11.54%, (OR = 0.004, 95% CI, 0.077-0.619) (P = 0.004). Dose reduction of chemotherapy or delay was 5% vs. 17.69% (OR = 0.245, 95% CI, 0.109-0.549) (P = 0.001). The prevention group had protective effects from all factors as compared to the delayed group (all P < 0.05, and all OR < 1). Moreover, the protective role of intravenous antibiotics was the strongest in the prevention group. CONCLUSION: Prophylactic use of GSF reduced hospitalization rate and the rate of intravenous application of antibiotics.