Stage IVb thymic carcinoma: patients with lymph node metastases have better prognoses than those with hematogenous metastases.

BACKGROUND: This study aimed to analyze the pattern of lymphogenous and hematogenous metastases in patients with stage IVb thymic carcinomas and identify prognostic factors for their survivals. METHODS: Between September 1978 and October 2014, 68 patients with pathologically confirmed stage IVb thymic carcinomas were treated at Fudan University Shanghai Cancer Center. Forty-three patients had lymph node involvement without distant metastases, and the remaining 25 patients had hematogenous metastases. Clinical-pathological characteristics, including age, sex, histologic subtype, tumor size, metastasis, treatment modalities, such as surgical resection, radiotherapy, and chemotherapy, and clinical outcomes, such as overall survival (OS) and progression free survival (PFS), were analyzed. RESULTS: The median follow-up time was 22 months (range, 1-126 months). The median OS of all patients with stage IVb thymic carcinomas was 30 months, and the 5-year overall survival rate was 25.1%. The median PFS was 11 months, and the 5-year PFS was 17.9%. Stage IVb patients with lymph node involvement had a better survival than those with distant metastasis (40 vs. 20 months, p = 0.002). Patients with myasthenia gravis had a worse prognosis (p = 0.033). Multivariate analysis identified metastatic status as an independent prognostic factor for OS in patients with stage IVb thymic carcinomas. CONCLUSIONS: Patients with lymph node involvement had a better survival than those with distant metastases. Much work remains to investigate the prognosis of patients with stage IVb thymic carcinomas and to explore different treatment strategies for patients with lymph node involvement and distant metastases.

N-Heterocyclic carbene-catalyzed cascade reaction of 2-aroylvinylcinnamaldehydes with 2-aroylvinylchalcones: rapid assembly of six contiguous stereogenic centers with high diastereoselectivity.

N-Heterocyclic carbene-catalyzed reaction of 2-aroylvinylcinnamaldehydes with 2-aroylvinylchalcones proceeded via a triple Michael addition and intramolecular lactonization cascade to produce novel 9-(2-aroyl-3-aroylmethyl-1-indanyl)-3-arylindeno[2,1-c]pyran-1-ones in good yields with high diastereoselectivity. This reaction constructed six contiguous stereogenic centers in a single reactive event. Among 32 possible diastereoisomers that contain six stereocenters, only two diastereoisomers were detected with diastereomeric ratios being 10 : 1-28 : 1. This work opens up a new avenue for the synthesis of complex indane derivatives, a type of compound that has been reported to possess various biological and pharmaceutical activities.

The impact of different modalities of chemoradiation therapy and chemotherapy regimens on lymphopenia in patients with locally advanced non-small cell lung cancer.

Background: Chemotherapy and radiotherapy (RT) would induce lymphopenia, leading to a poor prognosis. This study investigated whether chemotherapy increased lymphopenia during RT and explored the impacts of different chemotherapy regimens on the lymphocyte counts of patients receiving RT. Methods: Clinical parameters and lymphocyte data were collected from 215 patients with locally advanced non-small cell lung cancer (LA-NSCLC). Severe lymphopenia (SRL) was defined as an absolute lymphocyte count (ALC) of ≤0.2×103 cells/µL. Patient overall survival (OS) was analyzed using the Kaplan-Meier method. The predictors of SRL were extracted using univariate and multivariate regression analyses with backward likelihood ratio elimination. Results: Compared with patients without SRL, patients with SRL with LA-NSCLC showed a poorer prognosis in terms of OS (P=0.003). Of the 215 patients, 130 underwent concurrent chemoradiotherapy (CCRT) and 85 underwent sequential chemoradiotherapy (SCRT). The OS was better in patients without SRL (in the CCRT group, P=0.01 and in the SCRT group, P=0.08). The mean ALCs for CCRT and SCRT did not differ significantly (P=0.27). The minimum ALC of CCRT was significantly lower than that of SCRT (P<0.0001). CCRT was a predictor of SRL (P=0.008). However, multivariate analysis showed that the different chemotherapy regimens were not predictors of SRL (all P>0.1). Conclusions: In LA-NSCLC, the outcomes of patients with SRL were poorer than those without SRL. RT and chemotherapy were the main factors affecting SRL development, while different chemotherapy regimens were not significantly associated with lymphocyte counts in LA-NSCLC.

Long-term outcome of definitive radiotherapy for locally advanced non-small cell lung cancer: A real-world single-center study in the pre-durvalumab era.

BACKGROUND: There was limited research data on large-scale locally advanced non-small cell lung cancer (LA-NSCLC) radical radiotherapy (RT) reported in China. This study examined overall survival (OS), progression-free survival (PFS), treatment effectiveness, and toxicity in patients with LA-NSCLC treated with definitive RT in the pre-durvalumab era. METHODS: A retrospective analysis of demographic information, clinical characteristics, treatment patterns, and clinical outcomes of 789 patients with LA-NSCLC who underwent radical RT at our center between January 2005 and December 2015 was performed. The Kaplan-Meier method and log-rank test were used for survival comparisons, and Cox regression was used for multivariate analysis. RESULTS: There were 328 patients with stage IIIA disease and 461 with stage IIIB disease. By the last follow-up, there were 365 overall deaths and 576 cases of recurrence, metastasis, or death. The median survival time was 31 months. The OS rates at 1, 2, 5, and 10 years were 83.7%, 59.5%, 28.8%, and 18.9%, respectively. PFS rates at 1, 2, 5, and 10 years were 48%, 24.5%, 11.9%, and 5.5%, respectively. Rates of ≥grade 3 acute radiation pneumonitis or esophagitis were 7.6% and 1.9%, respectively. Rates of ≥grade 3 chronic radiation pneumonitis and esophagitis were 11% and 0.4%, respectively. Multivariate analysis showed that the Karnofsky Performance Status (KPS) score, smoking status, and combined chemotherapy were prognostic factors for OS (p < 0.05). Multivariate analysis revealed that combined chemotherapy and radiation dose were prognostic factors for PFS (p < 0.05). CONCLUSIONS: Our center's data showed that the survival prognosis of locally advanced patients receiving RT and chemotherapy in China was consistent with international levels during the same period. Patients with a KPS score of 80 or higher, who had never smoked or received combined RT, had a more favorable prognosis than those with a KPS of less than 80, who had smoked, or only received RT. The combination of RT and chemotherapy, with a reasonable radiation dose, was the key to improving the therapeutic effect.

Higher aorta dose increased neutrophil-to-lymphocyte ratio resulting in poorer outcomes in stage II-III non-small cell lung cancer.

BACKGROUND: This study focused on the relationship between the neutrophil-to-lymphocyte ratio (NLR) and the dose of organs at risk in patients with stage II-III non-small cell lung cancer (NSCLC) receiving intensity-modulated radiotherapy. METHODS: The clinical characteristics and dosimetric parameters of 372 patients were collected retrospectively. A high NLR was defined as that ≥1.525. Survival analysis was conducted using the Kaplan-Meier and Cox regression analysis. Least absolute shrinkage and selection operator (LASSO) analysis was conducted to select appropriate dosimetric parameters. The risk factors of NLR were evaluated using univariate and multivariate logistic regression analyses. RESULTS: Patients with a high NLR had poorer progression-free survival (PFS) (p = 0.011) and overall survival (OS) (p = 0.061). A low NLR (<1.525) predicted better PFS (hazard ratio [HR] 0.676, 95% confidence interval [CI]: 0.508-0.900, p = 0.007) and OS (HR 0.664, 95% CI: 0.490-0.901, p = 0.009). The aorta dose differed between the low and high NLR groups (all <0.1) in the univariate analysis. An aorta V10 was confirmed as a significant risk factor for a high NLR (odds ratio [OR] 1.029, 95% CI: 1.011-1.048, p = 0.002). Receiving chemotherapy before (OR 0.428, 95% CI: 0.225-0.813, p = 0.010) and during (OR 0.491, 95% CI: 0.296-0.815, p = 0.006) radiotherapy were predictive factors of a low NLR. CONCLUSION: The aorta dose was significantly associated with a high NLR. Patients with stage II-III NSCLC with a high NLR had poorer prognosis. Receiving chemotherapy before and/or during radiotherapy predicted a low NLR.

Failure patterns for thymic carcinoma with completed resection and postoperative radiotherapy.

BACKGROUND AND PURPOSE: We aimed to evaluate the pattern and risk factors of disease failure in patients with thymic carcinoma after complete resection and postoperative radiotherapy (PORT). MATERIALS AND METHODS: We retrospectively analyzed 127 patients with thymic carcinoma who underwent PORT after complete resection between 2003 and 2020 in our center. Data on clinical characteristics and radiation fields were collected. Failure patterns were recorded as locoregional (disease appearing in the tumor bed or regional lymph nodes), pleural, or distant failure (including hematogenous metastasis and nonregional lymph node metastasis). RESULTS: All patients underwent tumor bed irradiation. During a median follow-up period of 64 months, disease failure was observed in 51 patients (40.2 %). The 5-year disease-free survival (DFS) and overall survival rates were 58.9 % and 85.0 %, respectively. The sequence of failure patterns was distant (n = 41, 32.3 %), pleural (n = 28, 22.0 %), and locoregional failure (n = 19, 15.0 %). Of the locoregional failure patients, failures occurred in-field in three patients (2.4 %), marginal failure in one patient (0.8 %), out-of-field failure in nine patients (7.1 %), synchronous in-field and out-of-field failures in two patients (1.6 %), synchronous marginal and out-of-field failures in two patients (1.6 %), and unknown failure fields in two patients (1.6 %). Multivariate analysis showed that Masaoka stage (hazard ratio [HR], 3.88; p = 0.000) and adjuvant chemotherapy (HR, 0.47; p = 0.015) were independent predictors of DFS. CONCLUSION: The most common failure was distant, the Masaoka stage and adjuvant chemotherapy were independent predictors of DFS, and low locoregional failure-supported tumor bed irradiation was sufficient for patients with thymic carcinoma after complete resection.

Chemoradiotherapy with paclitaxel liposome plus cisplatin for locally advanced esophageal squamous cell carcinoma: A retrospective analysis.

PURPOSE: This single-center retrospective clinical study aimed to evaluate the efficacy and feasibility of chemoradiotherapy with paclitaxel liposome plus cisplatin for locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: Patients with locally advanced ESCC treated with paclitaxel-liposome-based chemoradiotherapy between 2016 and 2019 were retrospectively analyzed. Overall survival (OS) and progression-free survival (PFS) were evaluated using Kaplan-Meier analysis. RESULTS: Thirty-nine patients with locally advanced ESCC were included in this study. The median follow-up time was 31.5 months. The median OS time was 38.3 (95% confidence interval [CI]: 32.1-45.1) months, and the 1-, 2-, and 3-year OS rates were 84.6%, 64.1%, and 56.2%, respectively. The median PFS time was 32.1 (95% CI: 25.4-39.0) months, and the 1-, 2-, and 3-year PFS rates were 71.8%, 43.6%, and 43.6%, respectively. The most common Grade IV toxicity was neutropenia (30.8%) followed by lymphopenia (20.5%). There were no cases of Grade III/IV radiation pneumonia, and four patients (10.3%) had Grade III/IV esophagitis. CONCLUSION: Chemoradiotherapy using paclitaxel liposome and cisplatin is a well-tolerated and effective treatment regimen for locally advanced ESCC.

New prognostic system specific for epidermal growth factor receptor-mutated lung cancer brain metastasis.

Introduction: Brain metastases (BM) from lung cancer are heterogeneous, and accurate prognosis is required for effective treatment strategies. This study aimed to identify prognostic factors and develop a prognostic system exclusively for epidermal growth factor receptor (EGFR)-mutated lung cancer BM. Methods: In total, 173 patients with EGFR-mutated lung cancer from two hospitals who developed BM and received tyrosine kinase inhibitor (TKI) and brain radiation therapy (RT) were included. Univariate and multivariate analyses were performed to identify significant EGFR-mutated BM prognostic factors to construct a new EGFR recursive partitioning analysis (RPA) prognostic index. The predictive discrimination of five prognostic scoring systems including RPA, diagnosis-specific prognostic factors indexes (DS-GPA), basic score for brain metastases (BS-BM), lung cancer using molecular markers (lung-mol GPA) and EGFR-RPA were analyzed using log-rank test, concordance index (C-index), and receiver operating characteristic curve (ROC). The potential predictive factors in the multivariable analysis to construct a prognostic index included Karnofsky performance status, BM at initial lung cancer diagnosis, BM progression after TKI, EGFR mutation type, uncontrolled primary tumors, and number of BM. Results and discussion: In the log-rank test, indices of RPA, DS-GPA, lung-mol GPA, BS-BM, and EGFR-RPA were all significant predictors of overall survival (OS) (p ≤ 0.05). The C-indices of each prognostic score were 0.603, 0.569, 0.613, 0.595, and 0.671, respectively; The area under the curve (AUC) values predicting 1-year OS were 0.565 (p=0.215), 0.572 (p=0.174), 0.641 (p=0.007), 0.585 (p=0.106), and 0.781 (p=0.000), respectively. Furthermore, EGFR-RPA performed better in terms of calibration than other prognostic indices.BM progression after TKI and EGFR mutation type were specific prognostic factors for EGFR-mutated lung cancer BM. EGFR-RPA was more precise than other models, and useful for personal treatment.

Prophylactic cranial irradiation for limited-stage small-cell lung cancer in the magnetic resonance imaging era.

BACKGROUND: We investigated the role of prophylactic cranial irradiation (PCI) in limited-stage small-cell lung cancer (LS-SCLC) according to tumor response in the magnetic resonance imaging (MRI) era. METHODS: We retrospectively evaluated patients with LS-SCLC without brain metastases (BMs) on MRI who achieved either complete response (CR) or partial response (PR) after initial chemoradiotherapy at our center from 2006 to 2017. RESULTS: This study comprised 116 patients (median age, 58 years; men, 92; women, 24). After initial chemoradiotherapy, 53 patients achieved CR, while 63 patients achieved PR. Eighty-three patients received PCI. Patients who received PCI had better overall survival (OS, 5-year: 52.5% vs. 35.1%; p = 0.012) and progression-free survival (PFS, 5-year: 45.0% vs. 28.2%; p = 0.001) and a lower incidence of BMs (5-year: 18.3% vs. 39.4%; p = 0.010). In the subgroup analysis, PCI improved OS (5-year: 67.8% vs. 46.7%, p = 0.005) and PFS (5-year: 65.2% vs. 35.0%, p = 0.021) and decreased BM risk (5-year: 12.1% vs. 52.4%, p = 0.002) for patients with CR. However, PCI had no benefit (5-year OS: 40.5% vs. 35.6%, p = 0.763; 5-year BMs: 24.6% vs. 31.9%, p = 0.561) for patients with PR. CONCLUSIONS: Tumor response remained an important factor for selecting patients for PCI in the MRI era. PCI should be recommended for patients with LS-SCLC who achieve CR after initial thoracic chemoradiotherapy.

Proton and Carbon Ion Radiation Therapy Decreased Severe Lymphopenia by Reducing Thoracic Vertebra and Aortic Doses in Non-Small Cell Lung Cancer Versus Intensity Modulated Radiation Therapy.

PURPOSE: Lymphopenia is a common adverse effect of radiation therapy (RT). Little is known about the difference in lymphopenia between intensity modulated (photon) radiation therapy (IMRT) and proton and carbon ion radiation therapy (PCIRT). This study aimed to investigate lymphopenia differences between IMRT and PCIRT in non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: Clinical and dosimetric parameters were collected from 343 patients who received definitive IMRT or PCIRT for NSCLC. Severe lymphopenia (SRL) was defined as an absolute lymphocyte count (ALC) ≤0.5 × 103 cells/µL. Overall survival (OS) was analyzed using the Kaplan-Meier method. Propensity score matching was performed between the IMRT and PCIRT groups. Least absolute shrinkage and selection operator analysis was used to select appropriate dosimetric parameters. Univariate and multivariate logistic regression analyses were conducted to identify the predictors of SRL. RESULTS: Compared with the IMRT group, the PCIRT group was less likely to develop SRL (P < .001). Compared with the non-SRL group, the SRL group showed significant association with poorer OS, with a median survival time of 29.2 versus 15.0 months (P = .046). IMRT was an independent risk factor of SRL (P = .004). A lower ALC before RT (P = .030) and larger planning target volume (PTV) (P = .002) were also significant independent risk factors for SRL. Moreover, the majority of dosimetric parameters of organs at risk in PCIRT were lower than those in IMRT (P < .001). Thoracic vertebra V5 (P = .002) and aorta V5 (P = .026) were identified as independent risk predictors of SRL after adding dosimetric parameters to the regression model. CONCLUSIONS: Compared with IMRT, PCIRT could reduce SRL incidence, possibly by limiting thoracic vertebra and aortic doses, and SRL was associated with poor outcomes in patients with NSCLC.

NHC Brønsted base-catalyzed transformations of isochromene derivatives: regulation of products by the structures of carbene catalysts.

Two different transformations of α-(isochromen-1-yl)ketones catalyzed by NHC Brønsted bases are reported. In the presence of a triazole carbene, α-(isochromen-1-yl)ketones isomerized into ß-(2-(aroylmethylene)phenyl)-α,ß-unsaturated ketones in 38-88% yields, while the same reaction catalyzed by an imidazole carbene produced 1-aroylnaphthalene derivatives in 90-99% yields. This work not only provides a new method for the synthesis of a novel type of α,ß-unsaturated ketone and multi-substituted naphthalene derivatives, but also advances the application of NHC catalysts in the field of Brønsted base-catalysis.

Sequential boost of intensity-modulated radiotherapy with chemotherapy for inoperable esophageal squamous cell carcinoma: A prospective phase II study.

PURPOSE: This prospective phase II study aimed to determine the efficacy and tolerability of sequential boost of intensity-modulated radiation therapy (IMRT) with chemotherapy for patients with inoperable esophageal squamous cell carcinoma (ESCC). METHODS: Patients with histologically or cytologically proven inoperable ESCC were enrolled in this study (ChiCTR-OIC-17010485). A larger target volume for subclinical lesion was irradiated with 50 Gy, and then, a smaller target volume only including gross tumor was boosted to 66 Gy. The fraction dose was 2 Gy, and no elective node was irradiated. Concurrent and consolidation chemotherapy of fluorouracil (600 mg/m2 , days 1-3) plus cisplatin (25 mg/m2 , days 1-3) was administered every 4 weeks, for 4 cycles in total. The primary endpoint was 2-year progression-free survival (PFS). RESULTS: Eighty-eight patients were enrolled in this study. The median age was 65 years (range: 45-75 years), and 69 patients (78.4%) were men. With the median follow-up of 26 (range: 3-95) months, the 2- and 5-year PFS were 39.3% and 36.9%, respectively, and overall survival (OS) were 57.1% and 39.2%, respectively. Tumor stage and concurrent chemotherapy were independent OS predictors. Major acute adverse events were myelosuppression and esophagitis, most of which were grades 1-2. Nine percent and 2.3% of patients had grade 3 acute esophagitis and late esophageal strictures, respectively. CONCLUSIONS: Sequential boost to 66 Gy by IMRT with chemotherapy was safe and effective for inoperable ESCC. A randomized phase III study to compare with standard dose of 50 Gy is warranted.

Risk of Recurrence and Metastasis for Patients with T1N0M0 Esophageal Carcinoma Who Achieve Completed Resection via Endoscopic Submucosal Resection: Evidence for the Appropriateness of the Watch and Wait Follow-Up Strategy.

PURPOSE: Endoscopic submucosal dissection (ESD) is a widely performed procedure for esophageal carcinoma when the depth of invasion reaches the epithelium and lamina propria. However, ESD for esophageal carcinoma with depth of invasion exceeding the muscularis mucosa is controversial. This study aimed to evaluate the long-term outcomes of ESD for T1N0M0 (tumor invading the mucosa and submucosa [T1], no regional lymph node metastasis [N0], no distant metastasis [M0]) esophageal cancer. PATIENTS AND METHODS: Esophageal cancer was evaluated via pathology and computed tomography (CT) in consecutive patients with negative margin and without additional therapy. A total of 84 patients were included. The mean follow-up time was 42 (range, 9-99) months. RESULTS: No recurrence and metastasis were detected in the M1 and M2 group. The 5-year locoregional recurrence rate and distant metastasis rate were 4.2% and 5.6% for the M3 group and were 0% and 1.4% for the SM group, respectively. The 3- and 5-year overall survival were 94.4% (M1+M2 group, 95.0%; M3 group, 95.0%; SM group, 92.9%) and 80.9% (M1+M2 group, 95.0%; M3 group, 95.0%; SM group, 92.9%). Meanwhile, the 3- and 5-year disease-specific survival rates were 100% (M1+M2 group, 100%; M3 group, 100%; SM group, 100%) and 90.8% (M1+M2 group, 100%; M3 group, 90.0%; SM group, 85.7%). The major complications were postoperative strictures, most of which were grade 1-2. In total, two (4.8%) and one (1.2%) patient developed grade 3 and 5 late esophageal strictures, respectively. CONCLUSION: ESD complete resection yields low recurrence and metastasis rates in early esophageal cancer (T1N0M0). Thus, additional treatment is not necessary, and a watch and wait strategy may be reasonable.

Intensity Modulated Radiation Therapy Plus Etoposide/Cisplatin for Patients With Limited Advanced Unresectable Thymic Epithelial Tumors: A Prospective Phase 2 Study.

PURPOSE: This prospective phase 2 study evaluated the efficacy and safety of intensity modulated radiation therapy plus etoposide/cisplatin (EP) for patients with unresectable thymic epithelial tumors (TETs). METHODS AND MATERIALS: Patients with limited advanced unresectable TETs whose lesions could be encompassed within radiation fields were enrolled in this study. Two cycles of EP (75 mg/m2 etoposide and 25 mg/m2 cisplatin on days 1-3 and days 29-31) were administered concurrently with radiation therapy, followed by 2 cycles after radiation therapy. The primary endpoint was the objective response rate. The secondary endpoints were the progression-free survival rate, overall survival rate, and incidence of adverse events. RESULTS: Fifty-six patients were enrolled between June 2011 and May 2018. Twenty-two and 34 patients had thymomas and thymic carcinomas, respectively. The median age was 52 (range, 21-76) years, and 30 patients (53.6%) were men. Eight patients (14.3%) had stage III tumors, 6 (10.7%) had stage IVA tumors, and 42 (75.0%) had stage IVB tumors. The objective response rate was 85.7% (95% confidence interval, 76.3%-95.2%). With a median follow-up of 46 (range, 7-101) months, the 1-, 2-, and 5-year progression-free survival rates were 66.1%, 48.0%, and 29.5%, and the 1-, 2-, and 5-year overall survival rates were 91.0%, 76.2%, and 56.2%, respectively. The most common grade 3 to 4 adverse event was leukopenia (42.9%). Pulmonary fibrosis was also observed (5.3%). CONCLUSIONS: Because intensity modulated radiation therapy with EP is effective and safe for limited advanced unresectable TETs, it could be a suitable treatment option for such patients.

The prognostic value of tumor depth for cervical lymph node metastasis in hypopharyngeal and supraglottic carcinomas.

BACKGROUND: To analyze the prognostic value of the clinicopathological parameters of primary lesions for predicting cervical lymph node metastasis in patients with hypopharyngeal and/or supraglottic carcinoma. METHODS: We enrolled 127 patients with squamous cell carcinomas originating in the hypopharyngeal and/or supraglottic regions. RESULTS: Multivariate analysis identified the tumor depth as an independent predictive factor for lymph node metastasis (odds ratio, 4.959; 95% confidence interval, 2.290-10.739; P < 0.0001) with a predictive value of 0.966. A cutoff value of 4.5 mm was determined. CONCLUSION: The tumor depth of the primary lesion is a potent predictor of cervical lymph node metastasis in hypopharyngeal and supraglottic carcinomas. In cases with clinically negative nodal status, elective neck dissection should be adopted for patients with a tumor depth reaching 4.5 mm. Regular outpatient follow-up is recommended for patients with a tumor depth less than 1.0 mm. Close follow-up or preventative therapy should be considered between 1.0 and 4.5 mm.

Three-dimensional conformal radiation therapy alone for esophageal squamous cell carcinoma: 10-year survival outcomes.

BACKGROUND: Concurrent chemoradiation is the standard treatment for locally advanced esophageal squamous cell carcinoma (SCC). We conducted a phase II study to explore the effect of three-dimensional conformal radiotherapy (3-DCRT) alone for patients with locally advanced esophageal SCC. This study aimed to analyze the long-term survival outcomes. METHODS: Between November 2004 and April 2007, 30 patients with thoracic esophageal SCC underwent late-course sequential boost 3-DCRT at Fudan University Shanghai Cancer Center. The planning target volume (PTV1) comprised a 1.2-1.5 cm lateral margin around the gross tumor volume and a 3.0 cm margin, superior and inferior to the gross tumor volume. PTV2 encompassed the gross tumor volume with a margin of 0.5-0.7 cm. The PTV1 dose delivered was 50 Gy, and the PTV2 dose was a boost dose of 16 Gy, resulting in a total dose of 66 Gy. No chemotherapy was administered. RESULTS: The median follow-up time was 30 months for all patients, and 132 months for patients who were alive. The median overall survival was 27 months (95% confidence interval [CI] 18.9-35.0). The 2-, 5-, and 10-year overall survival rates were 56.6%, 33.3%, and 26.6%, respectively. The median progression-free survival was 14 months (95% CI 7.7-20.2 months), and the 2-, 5-, and 10-year progression-free survival rates were 33.3%, 30.0%, and 26.6%, respectively. No severe late toxicity was observed in long-term survivors. CONCLUSION: Late-course sequential boost 3-DCRT is safe and feasible with promising long-term outcomes for esophageal SCC.

Simultaneously avoiding the hippocampus and hypothalamic-pituitary axis during whole brain radiotherapy: A planning study.

Whole brain radiotherapy (WBRT) is the preferred treatment for multiple brain metastases, and patients with limited-stage small cell lung cancer undergo prophylactic cranial irradiation after complete remission. However, neurotoxicity remains a complication. In addition to protecting the hippocampus from irradiation to preserve cognitive function, it is also critical to avoid irradiating the hypothalamic-pituitary axis to preserve endocrine and immune function. This study aimed to evaluate the feasibility of delivering WBRT while protecting the hippocampus and hypothalamic-pituitary axis. Thirteen patients with limited-stage small cell lung cancer were enrolled in this study. The hippocampus, hypothalamus, and pituitary gland were contoured based on T1-weighted magnetic resonance imaging. The prescribed dose to the whole brain planning target volume was 25 Gy in 10 fractions. Two treatment plans using equispaced coplanar intensity-modulated radiotherapy (IMRT) were generated: WBRT with hippocampus avoidance (H-A) and WBRT with hippocampus, hypothalamus, and pituitary gland avoidance (H-HP-A). Both "H-A" and "H-HP-A" plans successfully protected the hippocampus, which received mean doses of 9.1 and 9.6 Gy, respectively (p = 0.0002), whereas the "H-HP-A" plan decreased the doses to both the hypothalamus (mean dose 11.06 Gy) and the pituitary gland (mean dose 10.66 Gy). Both "H-A" and "H-HP-A" plans showed similar target coverage of 95.1%. The homogeneity index of the "H-A" plan was slightly better than that of the "H-HP-A" plan (0.20 vs 0.23, p= 0.0012). In conclusion, the use of equispaced coplanar IMRT was found to simultaneously protect the hippocampus and hypothalamic-pituitary axis while delivering WBRT with acceptable target coverage and homogeneity.