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The effect of postoperative tegafur-uracil on overall survival (OS) after resection of stage I adenocarcinoma has been shown in clinical trials. The purpose of this study was to investigate whether findings from randomized trials of adjuvant tegafur-uracil are reproducible in a real-world setting.A retrospective cohort study was performed using a multi-institutional database that included all patients who underwent complete resection of pathological stage I adenocarcinoma between 2014 and 2016. Survival outcomes for patients managed with and without tegafur-uracil were analyzed using the Kaplan-Meier method and a Cox proportional hazards model for the whole patient cohort and in a selected cohort based on eligibility criteria of a previous randomized trial. Propensity score matching was used to adjust for confounding effects.After propensity score matching, the hazard ratios for OS were 0.57 (95% confidence interval (CI) 0.29-1.14, P = 0.11) in the whole cohort and 0.69 (95% CI 0.32-1.50, P = 0.35) in the selected cohort.The effects of tegafur-uracil in this retrospective study appear to be consistent with those found in randomized clinical trials. These effects may be maximized in patients aged from 45 to 75 years.

The aim of this trial was to address whether elective ipsilateral upper-neck irradiation (UNI) sparing the uninvolved lower neck provides similar regional relapse-free survival compared with standard whole-neck irradiation (WNI) in patients with nasopharyngeal carcinoma.This open-label, non-inferiority, randomised, controlled, phase 3 trial was done at three Chinese medical centres. Patients aged 18-65 years with untreated, non-keratinising, non-distant metastatic (M0) nasopharyngeal carcinoma; with N0-N1 disease (according to International Union Against Cancer-American Joint Committee on Cancer TNM classification, seventh edition); and a Karnofsky performance status score of 70 or higher were randomly assigned (1:1) to receive elective UNI or WNI of the uninvolved neck. Total radiation doses of 70 Gy (for the primary tumour volume and the enlarged retropharyngeal nodes), 66-70 Gy (for the involved cervical lymph nodes), 60-62 Gy (for the high-risk target volume), and 54-56 Gy (for the low-risk target volume) were administered in 30-33 fractions, five fractions per week. Patients with stage II-IVA disease were recommended to receive combined intravenous cisplatin-based chemotherapy (either induction chemotherapy followed by concurrent chemoradiotherapy or concurrent chemoradiotherapy alone). Randomisation was done centrally by the Clinical Trials Centre of Sun Yat-sen University Cancer Centre by means of a computer-generated random number code with a block size of four. Patients were stratified according to treatment centre and nodal status. Investigators and patients were not masked to treatment allocation. The primary endpoint was regional relapse-free survival in the intention-to-treat population. Non-inferiority was indicated if the upper limit of the 95% CI of the difference in 3-year regional relapse-free survival between the UNI and WNI groups was within 8%. Adverse events were analysed in the safety population (defined as all patients who commenced the randomly assigned treatment). This study is registered with ClinicalTrials.gov, NCT02642107, and is closed.Between Jan 22, 2016, and May 23, 2018, 446 patients from 469 screened were randomly assigned to receive UNI (n=224) or WNI (n=222). Median follow-up was 53 months (IQR 46-59). 3-year regional relapse-free survival was similar in the UNI and WNI groups (97·7% [95% CI 95·7-99·7] in the UNI group vs 96·3% [93·8-98·8] in the WNI group; difference -1·4% [95% CI -4·6 to 1·8]; pElective UNI of the uninvolved neck provides similar regional control and results in less radiation toxicity compared with standard WNI in patients with N0-N1 nasopharyngeal carcinoma.Sun Yat-sen University Clinical Research 5010 Program, the Natural Science Foundation of Guangdong Province, and the Overseas Expertise Introduction Project for Discipline Innovation.For the Chinese translation of the abstract see Supplementary Materials section.

Upper-neck irradiation (UNI) at the uninvolved neck has shown similar regional relapse-free survival as standard whole-neck irradiation (WNI) in N0-1 nasopharyngeal carcinoma patients. However, whether UNI at the contralateral uninvolved neck is feasible in unilateral N3 disease, defined as6 cm and/or below the caudal border of the cricoid cartilage, remains unclear.Data for 291 nasopharyngeal carcinoma patients with unilateral N3 disease, who were treated with intensity-modulated radiotherapy from 2009 to 2015, were retrospectively analyzed. Among them, 190 received bilateral WNI (WNI group); the remaining 101 received WNI at the involved neck and UNI at the contralateral uninvolved neck (UNI group). Survival rates were estimated using the Kaplan-Meier method and difference between groups were compared using the log rank tests.The median follow-up was 79.4 months (interquartile range, 56.0-89.3). Twenty-five patients had regional lymph node relapses (UNI: 10.9%, 11/101 vs. WNI: 7.4%, 14/190, p=0.31). Of these, 23 patients relapsed within the previously involved neck regions, while only two patients had relapses in the contralateral uninvolved neck (one each in the UNI and WNI groups). Five-year regional relapse-free survival rates were similar between groups (89.7% vs. 92.7%, p=0.29). Similar between-group findings were also observed for 5-year overall survival (76.1% vs. 80.4%, p=0.40), distant metastasis-free survival (74.9% vs. 79.2%, p=0.44), and local relapse-free survival (95.6% vs. 94.7%, p=0.64). Furthermore, oncologic outcomes in subgroup and multivariable analyses were similar between groups.Regional control and survival outcomes were comparable in UNI at the contralateral uninvolved neck and standard WNI in nasopharyngeal carcinoma patients with unilateral N3 disease. Our findings provide evidence for future radiotherapy guidelines of nasopharyngeal carcinoma.

Tumor‑associated macrophages (TAMs), particularly M2 macrophages, promote tumor progression, while

OBJECTIVES The aim of this study was to analyse the long-term survival outcomes and prognostic factors of patients receiving epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) as first-line treatment for postoperative recurrent EGFR-mutated lung adenocarcinoma. METHODS Using a multi-institutional database, we performed a retrospective chart review to identify all patients who had undergone complete resection of stage I–III EGFR-mutated lung adenocarcinoma at 11 acute care hospitals between 2009 and 2016 and had received first-line EGFR-TKI treatment for postoperative recurrence. Adverse events, progression-free survival (PFS) and overall survival (OS) were investigated. Survival outcomes were assessed using Kaplan–Meier analysis. Cox proportional hazards models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for PFS and OS. RESULTS The study sample comprised 154 patients with a median age of 69. The total numbers of events were 101 for PFS and 60 for OS. The median PFS and OS were 26.1 and 55.4 months, respectively. In the multivariable analysis, EGFR ex 21 L858R mutation (HR: 1.71, 95% CI: 1.15–2.55) and shorter disease-free intervals (HR: 0.98, 95% CI: 0.96–0.99) were significantly associated with shorter PFS. Age (HR: 1.03, 95% CI: 1.00–1.07), smoking history (HR: 2.31, 95% CI: 1.35–3.94) and pathological N2 disease at the initial surgery (HR: 2.30, 95% CI: 1.32–4.00) were significantly associated with shorter OS. CONCLUSIONS First-line EGFR-TKI treatment was generally associated with favourable survival outcomes in patients with postoperative recurrent EGFR-mutated lung adenocarcinoma. EGFR ex 21 L858R mutation may be an important prognostic factor for shorter PFS.

To improve the treatment strategy of immune‑checkpoint inhibitors for non‑small cell lung cancer (NSCLC), a comprehensive analysis of programmed death‑ligand (PD‑L)1 and PD‑L2 expression is clinically important. The expression of PD‑L1 and PD‑L2 on both tumor cells (TCs) and tumor‑infiltrating immune cells (ICs) was investigated, with respect to tumor‑infiltrating lymphocytes (TILs) and M2 tumor‑associated macrophages (TAMs), which are key components of the tumor microenvironment, in 175 patients with resected NSCLC. The TIL and M2 TAM densities were associated with the expression of PD‑L1 on the two TCs (both P0.0001) and ICs (both P0.0001). The TIL and M2 TAM densities were also associated with the expression of PD‑L2 on both TCs (P=0.0494 and P=0.0452, respectively) and ICs (P=0.0048 and P=0.0125, respectively). However, there was no correlation between the percentage of PD‑L1‑positive TCs and the percentage of PD‑L2‑positive TCs (r=0.019; P=0.8049). Meanwhile, tumor differentiation was significantly associated with the PD‑L1 expression on TCs and ICs (P=0.0002 and P0.0001, respectively). By contrast, tumor differentiation was inversely associated with the PD‑L2 expression on both TCs and ICs (P=0.0260 and P=0.0326, respectively). In conclusion, the combined evaluation of PD‑L1 and PD‑L2 expression could be clinically important in the treatment strategy of immune‑checkpoint inhibitors in patients with NSCLC. In particular, the evaluation of PD‑L2 expression may be necessary for patients with PD‑L1‑negative NSCLC.

Objectives To investigate the prognostic value of magnetic resonance imaging (MRI)‐determined cervical lymph node (CLN) size in nasopharyngeal carcinoma (NPC). Methods We retrospectively reviewed 2066 patients with NPC treated with intensity‐modulated radiotherapy, and randomly divided them into two groups, in a 1:1 ratio. One group was used for training (the training group), and the other one was for internal validation (the validation group). All patients had undergone MRI examination and the maximal axial diameters (MAD) of the axial plane of all positive nodes had been measured and recorded. Results Of 683 patients with CLN metastases in the training group (n = 1033), MAD = 4 cm was associated with worse OS (64.7% vs 84.6%, P, We identified the cut‐off value of the greatest diameter of lymph nodes on axial MRI slices, that is, MAD > 4 cm. MAD = 4 cm was associated with worse survival outcome in nasopharyngeal carcinoma. MAD == 4 cm could be recommended as a prognostic factor in future versions of the UICC/AJCC staging system.

There are few data available on the outcomes of postoperative recurrent thymic carcinoma (TC) and thymic neuroendocrine carcinoma (TNEC). The aim of this study is to evaluate the treatment and survival in patients with recurrent TC and TNEC after undergoing surgical resection. A retrospective chart review was performed using our multicenter database to identify patients with a postoperative recurrence of TC and TNEC from 1995 to 2018. The clinicopathological factors were reviewed and the survival outcomes were analyzed. Sixty patients were identified among 152 patients who underwent resection of TC and TNEC. The median follow-up period from the first recurrence was 14.8 months (range 0–144). The 5-year post-recurrence survival was 23% for the whole cohort. According to a univariable analysis, advanced stage [hazard ratio (HR) 2.81, 95% confidence interval (CI) 1.09–9.54], interval between primary surgery and recurrence (HR 0.97, 95% CI 0.95–0.99), any treatment for recurrence (HR: 0.27, 95% CI 0.13–0.58) and chemotherapy for recurrence (HR: 0.46, 95% CI 0.22–0.95) were significant factors related to post-recurrence survival. Chemotherapy rather than surgery appears to be the mainstay treatment for managing patients with postoperative recurrent TC and TNEC and it may also be considered in multidisciplinary management. Further studies with a larger sample size are required to confirm our findings.

This study aimed to investigate the association between the volume-dependent parameters in 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG PET/CT) and a recurrence of thymic carcinoma. A retrospective chart review was performed based on our multi-institutional database to identify patients undergoing PET prior to resection of thymic carcinoma or neuroendocrine carcinoma between 1991 and 2018. The PET parameters (metabolic tumor volume and total lesion glycolysis) were evaluated retrospectively. The relevant factors were extracted and a survival analysis was performed using the Kaplan–Meier method. Sixteen patients were thus deemed to be eligible for analysis. The median follow-up period following resection was 2.65 years (range: 0.96–0.68 years). The recurrence-free survival was significantly longer in patients with a metabolic tumor volume

Purpose In advanced gastric cancer, peritoneal dissemination is a life‐threatening mode of metastasis. Since the treatment options with conventional chemotherapy remain limited, any novel therapeutic strategy that could control such metastasis would improve the outcome of treatment. We recently developed a unique RNA interference therapeutic regimen (DFP‐10825) consisting of short hairpin RNA against thymidylate synthase (TS shRNA) and cationic liposomes. The treatment with DFP‐10825 has shown remarkable antitumor activity in peritoneally disseminated human ovarian cancer–bearing mice via intraperitoneal administration. In this study, we expanded DFP‐10825 to the treatment of peritoneally disseminated gastric cancer. Methods DFP‐10825 was administered intraperitoneally into mice with intraperitoneally implanted human gastric cancer cells (MKN45 or NCI‐N87). Antitumor activity and host survival benefits were monitored. Intraperitoneal distribution of fluorescence‐labeled DFP‐10825 was monitored in this MKN45 peritoneally disseminated mouse model. Results Intraperitoneal injection of DFP‐10825 suppressed tumor growth in two peritoneally disseminated cancer models (MKN45 and NCI‐N87) and increased the survival time of the MKN45 model without severe side effects. Throughout the treatment regimen, no significant body weight loss was associated with the administration of DFP‐10825. Interestingly, after intraperitoneal injection, fluorescence‐labeled DFP‐10825 retained for more than 72 hours in the peritoneal cavity and selectively accumulated in disseminated tumors. Conclusions Intraperitoneal injection of DFP‐10825 demonstrated effective antitumor activity without systemic severe adverse effects via the selective delivery of RNAi molecules into disseminated tumors in the peritoneal cavity. Our current study indicates that DFP‐10825 could become an alternative option to improve the outcomes of patients with peritoneally disseminated gastric cancer., Intraperitoneal DFP‐10825 showed effective antitumor activity in peritoneally disseminated human gastric cancer–bearing mice. As an alternative treatment regimen, DFP‐10825 has the potential to improve the outcomes of patients with peritoneally disseminated gastric cancer.

To compare the femoral and tibial tunnel positions of anterior cruciate ligament reconstruction using the modified transtibial (MTT) technique and anteromedial (AM) portal technique.Between January 2017 and September 2020, 78 patients with anterior cruciate ligament rupture underwent single-bundle reconstruction with the modified transtibial technique in 39 cases (group MTT) and through anteromedial approach in 39 cases (group AM). There were 25 males and 14 females in group MTT, with an average age of (37.0±2.3) years old; 27 males and 12 females in group AM, with an average age of (37.5±2.2) years old. CT scan of the affected knee was conducted one week after the surgery to measure and compare the femoral tunnels positioning (Fx, Fy), tibial tunnels positioning in the frontal plane(Tx1), tibial tunnels positioning in the sagittal plane (Ty1), and tibial tunnels positioning in the axial plane (Tx2, Ty2) in patients undergoing anterior cruciate ligament reconstruction through Mimics software.Three-dimensional CT reconstruction after the surgery showed that the average Fx and Fy were(25.2±2.1)% and (34.9±3.0)% respectively and the Tx1 and Ty1 were (45.5±3.3)% and (44.7± 3.0)% respectively, while the Tx2 and Ty2 were (47.0±3.0)% and (39.9±4.2)% respectively in group MTT. In group AM, the average Fx and Fy were (26.0±2.0)% and (36.1±3.9)% respectively and the Tx1 and Ty1 were (46.5±3.1)% and (45.6± 3.1)% respectively, while the Tx2 and Ty2 were (47.4±2.5)% and (39.6±3.9)% respectively. There were no statistically significant differences in the femoral and tibial tunnels between the two groups (Both the MTT and AM technique can achieve good anatomical positioning of the femoral and tibial tunnels, without significant differences in the positioning of the bone tunnels.

PurposeWe aimed to develop a prognostic immunohistochemistry (IHC) signature for patients with head and neck mucosal melanoma (MMHN).MethodsIn total, 190 patients with nonmetastatic MMHN with complete clinical and pathological data before treatment were included in our retrospective study.ResultsWe extracted five IHC markers associated with overall survival (OS) and then constructed a signature in the training set (n=116) with the least absolute shrinkage and selection operator (LASSO) regression model. The validation set (n=74) was further built to confirm the prognostic significance of this classifier. We then divided patients into high- and low-risk groups according to the IHC score. In the training set, the 5-year OS rate was 22.0% (95% confidence interval [CI]: 11.2%- 43.2%) for the high-risk group and 54.1% (95% CI: 41.8%-69.9%) for the low-risk group (PConclusionsA nomogram was generated and confirmed to be of clinical value. Our IHC classifier integrating five IHC markers could help clinicians make decisions and determine optimal treatments for patients with MMHN.

Carcinoma of unknown primary rarely occurs in the middle mediastinum. Here, we present three cases of carcinoma of unknown primary in the middle mediastinum, which were treated with surgical resection and adjuvant therapy. Positron emission tomography/computed tomography demonstrated high uptake of 18F-fluorodeoxyglucose in the tumors. Regarding the surgical procedure, dissection of the azygos vein was useful to obtain not only a good exposure of the surgical field but also mobilization of the superior vena cava, which led to safe separation of the tumors from the major mediastinal structures. The dissection and reconstruction of the superior vena cava was required due to extranodal invasion of the tumor in one case. Since the middle mediastinal carcinoma of unknown primary may be T0N2M0 NSCLC, the surgery alone seems to be insufficient treatment for this type of tumors. To evaluate whether the adjuvant therapy is associated with an improved prognosis for the patients with middle mediastinal carcinoma of unknown primary, a further accumulation of cases is required.

Background To identify thyroid dose‐volume thresholds for radiotherapy (RT)‐related hypothyroidism (HT) in patients with nasopharyngeal carcinoma (NPC) treated with intensity‐modulated RT (IMRT). In this way, we desired to guide the design of treatment plans and, finally, lower HT prevalence. Methods In total, 345 NPC patients treated with IMRT were evaluated retrospectively during a median follow‐up of 45.2 (range, 11.3‐64.9) months. Serum‐based assessments of thyroid function before and after IMRT were monitored periodically. Thyroid dose‐volume parameters were analyzed for their association with HT risk. Results In total, 44.1% of patients (152/345) developed primary HT. Analyses of thyroid dose‐volume parameters identified a stringent dose‐volume histogram (DVH) threshold defined by V 25Gy (the percentage thyroid volume that receives >25 Gy, not the absolute volume) ≤60%, V 35Gy ≤ 55%, and V 45Gy ≤ 45%. Patients whose thyroid DVHs satisfied these constraints had a lower prevalence of 2‐year HT compared with the overall prevalence (13.2% vs 25.8%, P 95%, V 35Gy > 90%, and V 45Gy > 75%, and patients whose thyroid DVHs satisfied with these constraints had a higher prevalence of 2‐year HT than the overall incidence (36.0% vs 25.8%, P 95%, V 35Gy > 90%, and V 45Gy > 75% as the “inhibition” DVH line, under the precondition of not compromising the target coverage. These findings could help in the design of individual treatment plans and, eventually, to lowering of HT prevalence., The risk of radiation‐related hypothyroidism (RHT) varied significantly depending on the dose‐volume parameters of thyroid radiation. We investigated and identified multiple thyroid dose‐volume thresholds for RHT in nasopharyngeal carcinomas treated with intensity‐modulated radiotherapy (RT), to guide risk stratification of RHT and help in the design of individual RT plans.

RNA interference (RNAi) is one of the most promising strategies for cancer therapeutics. The successful translation of RNAi therapeutics to a clinic setting requires a delivery system that is efficient and simple to upscale. In this study, we devised a simple industrial method to manufacture lipoplex, which includes short hairpin RNA against the expression of thymidylate synthase (TS shRNA) - a key molecule for DNA biosynthesis. An aqueous solution of TS shRNA was gently mixed with either a precursor of cationic liposome (Presome DF-1) or a cationic lipid mixture in an o/w emulsion. This solution was subsequently lyophilized under optimal conditions to obtain either FD-lipoplex-1 or FD-lipoplex-2, respectively. With this method, a lipoplex in activated form was obtained via a simple "one-step" hydration with saline. Both forms of FD-lipoplex showed physicochemical properties comparable to those of conventional lipoplex. FD-lipoplexes stably retained TS shRNA within their formulations in the presence of tumor ascites fluid. Intraperitoneal treatment with either FD-lipoplex-1 or FD-lipoplex-2 provided a therapeutic level of efficacy comparable to that of conventional lipoplex in the treatment of a peritoneal disseminated gastric cancer mouse model. Collectively, established freeze-drying-based methods for RNAi-therapeutic preparation could realistically be used in a clinical setting for the treatment of patients with peritoneal disseminated cancer.

Background Intensity‐modulated radiotherapy (IMRT) provides excellent local control in nasopharyngeal carcinoma (NPC). We investigated whether simplifying 8th American Joint Committee on Cancer staging system T categories improves prognostic value. Methods We used 2191 NPC patients as a training set and 414 patients separately as an independent, external validation cohort. Results In the training set, local relapse‐free survival (LRFS), disease‐free survival (DFS), and overall survival (OS) were not significantly different between the 8th edition T2/T3 (P = 0.610, 0.380 and 0.353, respectively). Merging T2 and T3 to proposed T2 (proT2) provided significant differences in LRFS, DFS, and OS between proposed T categories. Proposed T categories had similar c‐indices for LRFS, DFS, and OS (vs the 8th edition), which was validated in the external cohorts. Moreover, for DFS, the adjusted HRs of the proT2N0 (3.8), proT1N1 (3.8), and proT2N1 (6.0) subsets were similar; the adjusted HRs of the proT3N0 (7.0), proT3N1 (11.4), proT1N2 (11.0), proT2N2 (11.6), and proT3N2 (13.3) subsets were similar; the adjusted HRs of the proT1N3 (17.8), proT2N3 (15.3), and proT3N3 (26.4) subsets were similar; the results of the adjusted HRs for OS had the same rule. Defining proT1N0 as stage I; proT1N1/proT2N0‐1 as stage II; proT3N0‐2/proT1‐2N2 as stage III; and proT1‐3N3 as stage IVa generated orderly, significant differences in DFS and OS between stages in the training set and external validation cohort. Conclusions In the IMRT era, three T categories are more reasonable (merging T2/T3 into T2) and proT3N0‐2 (the 8th edition T4N0‐2) should be down‐staged to stage III.

9111 Background: DFP-14323(INN: ubenimex) was developed as a biological response modifier and has been approved for maintenance therapy of AML in Japan. Ubenimex is an inhibitor of aminopeptidase N (APN), originated from Streptomyces olivoreticuli. APN is well known as one of the prognostic factors for several cancer types, including non-small-cell lung cancer (NSCLC). Meanwhile, afatinib is one of the standard treatments in NSCLC with EGFR mutation, but the toxicities often require dose reduction. Recently, it is suggested that reducing afatinib doses can decrease treatment-related adverse events without affecting efficacy. We aimed to examine efficacy of DFP-14323 with low-dose afatinib by conducting phase II study in patients with metastatic NSCLC harboring EGFR mutation. Methods: The study was a multi-center, single-arm, open-label phase II trial. Stage III/IV and treatment-naïve patients with common EGFR mutation-positive (L858R/19del) NSCLC were treated with DFP-14323 at a fixed dose of 10mg/day and afatinib at a starting dose of 20 mg/day until disease progression or intolerable toxicity. The primary endpoint was disease control rate (DCR), defined by sum the CR, PR and SD. The secondary endpoints were progression-free survival(PFS), overall response rate(ORR), N/L ratio, and safety. A sample size of 26 patients was determined, assuming a threshold DCR 70% and an expected DCR 90% with a two sided α error of 0.05 and a β error of 0.20, based on the Simon’s two stage design. Results: From July 2018 to March 2020, 26 patients were enrolled. A median age was 72 years (range, 53-82), 21(81%) were female, and 16 (62%) were never-smokers. Half of patients had Del-19 and other half had L858R. An efficacy analysis provided a DCR of 100% (previously reported) with 18 responders (ORR : 69%). Independent imaging evaluation at 72 weeks provided a median PFS was confirmed to be 16.6mts (95% CI 10.2, 22.9, median follow-up time for censored cases: 16.3mts). According to updated exploratory follow-up by physicians, as of the data cut-off of Dec 2021, median PFS was calculated 20.6 mts (95% CI, 12.6, 28.5, median follow-up time for censored case: 20.9mts). Seven Grade 3 adverse events were observed in 6patient(23%), and paronychias in 3 patients and diarrhea, stomatitis, dermatitis, and lymphocytopenia in 1 patient each. One paronychia was considered to be related to DFP-14323 and the other events to afatinib. No grade 4 or 5 adverse events were observed. One Grade 1 ILD was observed but recovered soon without treatment. Conclusions: Combination of DFP-14323 and low-dose afatinib has shown comparable potential as a first-line treatment for EGFR mutation positive NSCLC with feasible efficacy and good safety profile. We are planning a phase III study to evaluate this combination therapy as compared with other EGFR-TKIs. Clinical trial information: UMIN000033062.

Minimally invasive surgery (MIS) has occasionally been used for selected patients with thymoma, but there is little information on the MIS approach for thymic carcinoma. The aim of this study was to evaluate survival outcomes after MIS for early-stage (Masaoka stage I-II) thymic carcinoma and thymic neuroendocrine carcinoma. A retrospective chart review of the cases recorded in our multi-institutional database was performed to identify patients who underwent resection for thymic carcinoma between 1995 and 2017. MIS thymectomy was performed in 17 cases (VATS, n = 14; RATS, n = 3. male, 41%; median age, 72 years). The median follow-up period was 32.7 (range 7.4-106) months. The five-year overall survival and relapse-free survival rates were 84.4% and 77.8%, respectively. The present study demonstrated encouraging preliminary results regarding MIS for the treatment of early-stage thymic carcinoma and thymic neuroendocrine carcinoma. Further studies with a larger sample size are required to evaluate the indications for this surgery.

Objectives Previous studies have suggested that a second malignancy often develops after resection of thymoma; however, it remains unknown whether this is applicable to thymic carcinoma. Methods A retrospective chart review was performed based on our multi-institutional database of resected thymic epithelial tumours between 1991 and 2016. A second malignancy was defined as newly diagnosed after thymic tumour resection. The cumulative incidence of and related death from a second malignancy after thymic and neuroendocrine carcinoma resections were estimated using a competing risk model and were compared to those of patients undergoing a thymoma resection. Results Two hundred and thirty-eight patients were identified (thymic carcinoma 59; thymoma 179). A second malignancy developed in 1 patient (1.7%) with thymic carcinoma and in 17 patients (9.5%) with thymoma. Deaths from second malignancies were noted in 7 patients with thymoma. There was a tendency towards a lower cumulative incidence of and a lower cumulative death from a second malignancy after thymic carcinoma resection (P = 0.139 and P = 0.20, respectively) than after thymoma resection. The cumulative incidence of a second malignancy in patients with thymic carcinoma was 2.8% at 5 years and at 10 years (8.0% at 5 years and 11.8% at 10 years in patients with thymoma). Conclusions After resection of thymic and thymic neuroendocrine carcinoma, the probability of developing a second malignancy, as well as mortality from a second malignancy, is very low. A prospective study with a larger sample size is required to validate our results.

BackgroundIn locoregionally advanced nasopharyngeal carcinoma (LANPC) patients, variance of tumor response to induction chemotherapy (ICT) was observed. We developed and validated a novel imaging biomarker to predict which patients will benefit most from additional ICT compared with chemoradiotherapy (CCRT) alone.MethodsAll patients, including retrospective training (n = 254) and prospective randomized controlled validation cohorts (a substudy of NCT01245959,n = 248), received ICT+CCRT or CCRT alone. Primary endpoint was failure-free survival (FFS). From the multi-parameter magnetic resonance images of the primary tumor at baseline, 819 quantitative 2D imaging features were extracted. Selected key features (according to their interaction effect between the two treatments) were combined into an Induction Chemotherapy Outcome Score (ICTOS) with a multivariable Cox proportional hazards model using modified covariate method. Kaplan-Meier curves and significance test for treatment interaction were used to evaluate ICTOS, in both cohorts.ResultsThree imaging features were selected and combined into ICTOS to predict treatment outcome for additional ICT. In the matched training cohort, patients with a high ICTOS had higher 3-year and 5-year FFS in ICT+CCRT than CCRT subgroup (69.3% vs. 45.6% for 3-year FFS, and 64.0% vs. 36.5% for 5-year FFS; HR = 0.43, 95% CI = 0.25–0.74,p = 0.002), whereas patients with a low ICTOS had no significant difference in FFS between the subgroups (p = 0.063), with a significant treatment interaction (pinteraction n = 73, ICT+CCRT 89.7% and 89.7% vs. CCRT 61.8% and 52.8% at 3-year and 5-year; HR = 0.17, 95% CI = 0.06–0.51,p n = 175,p = 0.31), with a significant treatment interaction (pinteraction = 0.019). Compared with 12.5% and 16.6% absolute benefit in the validation cohort (3-year FFS from 69.9 to 82.4% and 5-year FFS from 63.4 to 80.0% from additional ICT), high ICTOS group in this cohort had 27.9% and 36.9% absolute benefit. Furthermore, no significant survival improvement was found from additional ICT in both groups after stratifying low ICTOS patients into low-risk and high-risks groups, by clinical risk factors.ConclusionAn imaging biomarker, ICTOS, as proposed, identified patients who were more likely to gain additional survival benefit from ICT+CCRT (high ICTOS), which could influence clinical decisions, such as the indication for ICT treatment.Trial registrationClinicalTrials.gov,NCT01245959. Registered 23 November 2010.