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Background: Systemic therapy is the primary treatment for advanced thymic malignancies. However, there is an urgent need to improve clinical outcome. Personalized treatment based on predictive biomarkers is a potential approach to address this requirement. In this study, we aimed to show the correlation between drug sensitivity tests on CTCs‐derived organoids and clinical response in patients with thymic malignancies. This approach carries the potential to create personalized cancer avatars and improve treatment outcome for patients. Methods: We previously reported potential treatment outcome prediction with patient‐derived organoids (cancer avatars) in patients with pancreatic ductal adenocarcinoma. To further investigate the feasibility of this approach in advanced thymic malignancies, we conducted a study in which 12 patients were enrolled and 21 liquid biopsies were performed. Results: Cancer avatars were successfully derived in 16 out of 21 samples (success rate 76.2%). We found a sensitivity of 1.0 and specificity of 0.6 for drug sensitivity tests on the cancer avatars, and a two‐tailed Fisher's exact test revealed a significant correlation between drug sensitivity tests and clinical responses (p = 0.0275). Conclusion: This study supports the potential of circulating tumor cell‐derived organoids to inform personalized treatment for advanced thymic malignancies. Further validation of this proof of concept finding is ongoing. [ABSTRACT FROM AUTHOR]

Simple Summary: Boron neutron capture therapy (BNCT) is a target radiotherapy and image-guided intensity-modulated radiotherapy (IG-IMRT) that has been used for recurrent head and neck cancer. To procure better results, the current study designed to combine both as salvage treatment for this challenging problem. For the 14 patients enrolled, a high response rate and low incidence of grade 4 toxicity were seen at follow-up. Further local recurrence was the main cause of failure in spite of the larger radiation volumes and extra dose given with IG-IMRT after BNCT than with BNCT alone. Further revision of this protocol is suggested to improve our results. Background: This trial investigated the efficacy and safety of salvage boron neutron capture therapy (BNCT) combined with image-guided intensity-modulated radiotherapy (IG-IMRT) for recurrent head and neck cancer after prior radiotherapy (RT). Methods: BNCT was administered using an intravenous boronophenylalanine–fructose complex (500 mg/kg) in a single fraction; multifractionated IG-IMRT was administered 28 days after BNCT. For BNCT, the mucosa served as the dose-limiting organ. For IG-IMRT, the clinical target volume (CTV) and the planning target volume (PTV) were generated according to the post-BNCT gross tumor volume (GTV) with chosen margins. Results: This trial enrolled 14 patients, and 12 patients received combined treatment. The median BNCT average dose for the GTV was 21.6 Gy-Eq, and the median IG-IMRT dose for the PTV was 46.8 Gy/26 fractions. After a median (range) follow-up period of 11.8 (3.6 to 53.2) months, five patients had a complete response and four had a partial response. One patient had grade 4 laryngeal edema; another patient had a grade 4 hemorrhage. Most tumor progression occurred within or adjacent to the CTV. The 1-year overall survival and local progression-free survival rates were 56% and 21%, respectively. Conclusion: Despite the high response rate (64%) of this trial, there was a high incidence of in-field and marginal failure with this approach. Future studies combining BNCT with modalities other than radiation may be tried. [ABSTRACT FROM AUTHOR]

Background: Stereotactic ablative radiotherapy (SABR) is now the standard of care for patients with inoperable early‐stage lung cancer. Many of these patients are elderly. EGFR (epidermal growth factor receptor) mutation is also common in the Asian population. Methods: To evaluate the effects of old age and EGFR mutation on treatment outcomes and toxicity, we reviewed the medical records of 71 consecutive patients with inoperable early‐stage non‐small cell lung cancer (NSCLC) who received SABR at Taipei Veterans General Hospital between 2015 and 2021. Results: The study revealed that median age, follow‐up, Charlson comorbidity index, and ECOG score were 80 years, 2.48 years, 3, and 1, respectively. Of these patients, 37 (52.1%) were 80 years or older, and 50 (70.4%) and 21 (29.6%) had T1 and T2 diseases, respectively. EGFR mutation status was available for 33 (46.5%) patients, of whom 16 (51.5%) had a mutation. The overall survival rates at 1, 3, and 5 years were 97.2, 74.9, and 58.3%, respectively. The local control rate at 1, 3, and 5 years was 97.1, 92.5, and 92.5%, respectively. Using Cox proportional hazards regression we found that male sex was a risk factor for overall survival (p = 0.036, 95% CI: 1.118–26.188). Two patients had grade 2 pneumonitis, but no other grade 2 or higher toxicity was observed. We did not find any significant differences in treatment outcomes or toxicity between patients aged 80 or older and those with EGFR mutations in this cohort. Conclusion: These findings indicate that age and EGFR mutation status do not significantly affect the effectiveness or toxicity of SABR for patients with inoperable early‐stage NSCLC. [ABSTRACT FROM AUTHOR]

Background: We aimed to analyze the radiation dose and compare survival among combined modality therapy using modern radiation techniques for patients with esophageal squamous cell carcinoma (ESCC). Methods: This retrospective study included patients with clinically staged T1‐4N0‐3M0 ESCC from 2014 to 2018. Patients who received combined modality therapies with curative intent were enrolled. The overall survival (OS) rates among combined modality therapy were compared. The clinical variables and impacts of radiation dose on survival were analyzed by the Kaplan–Meier method and Cox regression model. Results: Of the 259 patients, 141 (54.4%) received definitive concurrent chemoradiotherapy (DCCRT); 67 (25.9%) underwent neoadjuvant chemoradiotherapy followed by surgery (NCRT+S); 51 (19.7%) obtained surgery followed by adjuvant chemoradiotherapy (S+ACRT). Two‐year OS rates of the DCCRT, NCRT+S and S+ACRT group were 48.9, 61.5 and 51.2%. In the subgroup analysis of DCCRT group, the 2‐year OS of patients receiving radiation dose 55–60 Gy was 57.1%. Multivariate analyses showed that clinical stage (p = 0.004), DCCRT with 55–60 Gy (p = 0.043) and NCRT+S with pathological complete response (pCR) (p = 0.014) were significant prognostic factors for better OS. The radiation dose–survival curve demonstrated a highly positive correlation between higher radiation dose and better survival. Conclusion: Our results suggest that NCRT+S can provide a favorable survival for patients with ESCC, especially in patients who achieved pCR. The optimal radiation dose might be 55–60 Gy for patients receiving DCCRT via modern radiation techniques. Further randomized clinical studies are required to confirm the survival benefits between NCRT+S and DCCRT with escalated dose. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is highly aggressive and has poor prognosis. There are few biomarkers to inform treatment decisions, and collecting tumour samples for testing is challenging. Circulating tumour cells (CTCs) from patients with PDAC liquid biopsies were expanded ex vivo to form CTC-derived organoid cultures, using a laboratory-developed biomimetic cell culture system. CTC-derived organoids were tested for sensitivity to a PDAC panel of nine drugs, with tests conducted in triplicate, and a weighted cytotoxicity score (CTS) was calculated from the results. Clinical response to treatment in patients was evaluated using Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 criteria at the time of blood sampling and 3 months later. The correlation between CTS and clinical response was then assessed. A total of 41 liquid biopsies (87.8% from patients with Stage 4 disease) were collected from 31 patients. The CTC-derived organoid expansion was achieved in 3 weeks, with 87.8% culture efficiency. CTC-derived organoid cultures were positive for EpCAM staining and negative for CD45 staining in the surface marker analysis. All patients had received a median of two lines of treatment prior to enrolment and prospective utility analysis indicated significant correlation of CTS with clinical treatment response. Two representative case studies are also presented to illustrate the relevant clinical contexts. CTCs were expanded from patients with PDAC liquid biopsies with a high success rate. Drug sensitivity profiles from CTC-derived organoid cultures correlated meaningfully with treatment response. Further studies are warranted to validate the predictive potential for this approach. • Circulating tumour cells (CTCs) from patients with pancreatic ductal adenocarcinoma were collected and expanded ex vivo to form organoids. • CTC-derived organoids were tested for sensitivity to a panel of pancreatic ductal adenocarcinoma treatments. • Drug sensitivity results correlated with clinical outcomes in patients. • First study to correlate drug sensitivity results from CTCs with clinical outcomes. • This system can potentially facilitate treatment selection and monitor resistance. [ABSTRACT FROM AUTHOR]

Purpose: Complications can occur following a prolonged latency period after radiation therapy for cancer, and this is a growing concern because secondary tumors are potentially fatal. Few studies have examined secondary tumors in patients who received radiation therapy as children.Methods and Materials: This retrospective study examined 1697 pediatric patients with central nervous system tumors who received treatment at Taipei Veterans General Hospital from January 1, 1975, to December 31, 2013. Secondary tumors developed in 27 of 681 patients who received cranial irradiation. Overall survival was estimated using the Kaplan-Meier method, and the significance of differences was determined by the log-rank test.Results: The overall cumulative incidence of secondary tumors at 25 years was 3.96%, and there were similar numbers of male patients (n = 16) and female patients (n = 11). The mean age at diagnosis was 8.8 years (range, 3-16.5 years), the median dose of cranial irradiation was 52.5 Gy (mean, 53.4 Gy), the mean latency period was 14.6 years (range, 2-33 years), and the mean age at diagnosis of a secondary tumor was 23.1 years. The secondary tumors were mainly meningiomas (n = 13), sarcomas (n = 7), and high-grade gliomas (n = 6), and the mean latency periods were 19.66, 8.00, and 10.83 years, respectively. The overall survival rate from these secondary tumors was significantly different (P < .05). Age at irradiation of <7 years and craniospinal irradiation significantly increased the risk of a secondary tumor (P < .05). Secondary tumors developed in 11 of 128 patients (8.6%) with primary medulloblastomas, which was higher than the overall cumulative incidence.Conclusions: Clinicians should consider the increased risk of secondary tumors in long-term cancer survivors who received craniospinal irradiation as children. Using a selective dose de-escalation strategy or deferring radiation therapy for young patients at highest risk of secondary cancers should be studied. [ABSTRACT FROM AUTHOR]

Abstract: To introduce our experience of treating locally and regionally recurrent head and neck cancer patients with BNCT at Tsing Hua Open-Pool Reactor in Taiwan, 12 patients (M/F=10/2, median age 55.5 Y/O) were enrolled and 11 received two fractions of treatment. Fractionated BNCT at 30-day interval with adaptive planning according to changed T/N ratios was feasible, effective and safe for selected recurrent head and neck cancer in this trial. [Copyright &y& Elsevier]