Purpose: There is few evidence regarding the optimal salvage treatment options for loco-reginal recurrence of esophageal cancer. This study aimed to evaluate the clinical outcomes of salvage radiotherapy (RT) in patients with loco-regional recurrence (LRR) after surgery for esophageal cancer. Materials and Methods: We retrospectively reviewed 147 esophageal cancer patients who received salvage RT for loco-regional recurrence between 1996 and December 2019. A total dose of 60 Gy in 20 fractions was used for RT alone and 60-70 Gy in 30-35 fractions for concurrent chemoradiotherapy (CCRT). Results: The patients’ median age was 65 years (range, 41 to 86 years). The median disease-free interval was 13.5 months (1.0 to 97.4 months). After a median 18.8 months follow-up, the 2-year overall survival (OS) and progression-free survival (PFS) rates were 38.1% and 25.9%, respectively. The median OS and PFS were 18.8 and 8.4 months, respectively. The CCRT could not improve OS compared to RT (p=0.336), but there was a trend of better PFS in the CCRT group. Regarding toxicities, the rate of grade 3 or higher toxicity was 10.9% occurring in 16 patients, and it was higher in patients who received CCRT than in the RT alone group (19.6% vs. 6.3%, p=0.023). Conclusion Salvage RT alone as well as CCRT could be effective in patients with locoregionally recurrent esophageal cancer.

Purpose: There is few evidence regarding the optimal salvage treatment options for loco-reginal recurrence of esophageal cancer. This study aimed to evaluate the clinical outcomes of salvage radiotherapy (RT) in patients with loco-regional recurrence (LRR) after surgery for esophageal cancer. Materials and Methods: We retrospectively reviewed 147 esophageal cancer patients who received salvage RT for loco-regional recurrence between 1996 and December 2019. A total dose of 60 Gy in 20 fractions was used for RT alone and 60-70 Gy in 30-35 fractions for concurrent chemoradiotherapy (CCRT). Results: The patients’ median age was 65 years (range, 41 to 86 years). The median disease-free interval was 13.5 months (1.0 to 97.4 months). After a median 18.8 months follow-up, the 2-year overall survival (OS) and progression-free survival (PFS) rates were 38.1% and 25.9%, respectively. The median OS and PFS were 18.8 and 8.4 months, respectively. The CCRT could not improve OS compared to RT (p=0.336), but there was a trend of better PFS in the CCRT group. Regarding toxicities, the rate of grade 3 or higher toxicity was 10.9% occurring in 16 patients, and it was higher in patients who received CCRT than in the RT alone group (19.6% vs. 6.3%, p=0.023). Conclusion Salvage RT alone as well as CCRT could be effective in patients with locoregionally recurrent esophageal cancer.

Purpose: There is few evidence regarding the optimal salvage treatment options for loco-reginal recurrence of esophageal cancer. This study aimed to evaluate the clinical outcomes of salvage radiotherapy (RT) in patients with loco-regional recurrence (LRR) after surgery for esophageal cancer. Materials and Methods: We retrospectively reviewed 147 esophageal cancer patients who received salvage RT for loco-regional recurrence between 1996 and December 2019. A total dose of 60 Gy in 20 fractions was used for RT alone and 60-70 Gy in 30-35 fractions for concurrent chemoradiotherapy (CCRT). Results: The patients’ median age was 65 years (range, 41 to 86 years). The median disease-free interval was 13.5 months (1.0 to 97.4 months). After a median 18.8 months follow-up, the 2-year overall survival (OS) and progression-free survival (PFS) rates were 38.1% and 25.9%, respectively. The median OS and PFS were 18.8 and 8.4 months, respectively. The CCRT could not improve OS compared to RT (p=0.336), but there was a trend of better PFS in the CCRT group. Regarding toxicities, the rate of grade 3 or higher toxicity was 10.9% occurring in 16 patients, and it was higher in patients who received CCRT than in the RT alone group (19.6% vs. 6.3%, p=0.023). Conclusion Salvage RT alone as well as CCRT could be effective in patients with locoregionally recurrent esophageal cancer.

Purpose: Optimal treatment for stage IIIA/N2 non–small cell lung cancer (NSCLC) is controversial. We aimed to assess the efficacy and safety of adjuvant pembrolizumab for stage IIIA/N2 NSCLC completely resected after neoadjuvant concurrent chemoradiation therapy (CCRT). Materials and Methods: In this open-label, single-center, single-arm phase 2 trial, patients with stage IIIA/N2 NSCLC received adjuvant pembrolizumab for up to 2 years after complete resection following neoadjuvant CCRT. The primary endpoint was disease-free survival (DFS). Secondary endpoints included overall survival (OS) and safety. As an exploratory biomarker analysis, we evaluated the proliferative response of blood CD39+PD-1+CD8+ T cells using fold changes in the percentage of proliferating Ki-67+ cells from days 1 to 7 of cycle 1 (Ki-67D7/D1). Results: Between October 2017 and October 2018, 37 patients were enrolled. Twelve (32%) and three (8%) patients harbored EGFR and ALK alterations, respectively. Of 34 patients with programmed cell death ligand 1 assessment, 21 (62%), nine (26%), and four (12%) had a tumor proportion score of < 1%, 1%-50%, and ≥ 50%, respectively. The median follow-up was 71 months. The median DFS was 22.4 months in the overall population, with a 5-year DFS rate of 29%. The OS rate was 86% at 2 years and 76% at 5 years. Patients with tumor recurrence within 6 months had a significantly lower Ki-67D7/D1 among CD39+PD-1+CD8+ T cells than those without (p=0.036). No new safety signals were identified. Conclusion Adjuvant pembrolizumab may offer durable disease control in a subset of stage IIIA/N2 NSCLC patients after neoadjuvant CCRT and surgery.

Background: Despite the extraordinary speed of mass vaccination efforts, an outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) delta variant in a vaccinee with coronavirus disease 2019 (COVID-19) mRNA vaccine was identified in an adult day service center (ADSC) of Jeju, South Korea. The primary objective of this study was to investigate the epidemiologic features in infection-vulnerable facilities with a high vaccination rate of BNT162b2 mRNA COVID-19 vaccine. The second was to estimate the secondary transmission prevention effect of the vaccine in the household members by vaccination status. Methods: We included all ADSC participants, staff and their household members. All COVID-19 infected cases were confirmed by reverse transcriptase polymerase chain reaction.We calculated attack rate in ADSC and the secondary attack rate (SAR) in household members by vaccination status. Results: Among a total of 42 participants and 16 staff, of which 96.6% were fully vaccinated with BNT162b2 mRNA COVID-19 vaccine, 12 symptomatic cases and 13 asymptomatic confirmed cases of COVID-19 were found. The attack rate was 43.1%, with 13 isolates identified as SARS-CoV-2 virus, delta variant. The SAR in unvaccinated and partially vaccinated household members were 27.8% (5/18) and 25.0% (5/20), respectively, while the SAR in fully vaccinated household members was 12.5% (1/8). Conclusion We describe a SARS-CoV-2 delta variant outbreak in ADSC with high vaccine coverage rate, characterized by high infection rate, high transmissibility, and low clinical severity. The outbreak proceeded to unvaccinated or partially vaccinated household members, emphasizing the need for immunizing close contacts of high-risk groups.

Clinical trials have not consistently supported the use of induction chemotherapy (IC) for locally advanced head and neck squamous cell cancer. Hypopharynx and base of tongue (BOT) cancer has shown relatively poor survival. We investigated the role of IC in improving outcome over current chemoradiotherapy (CRT) in patients with hypopharynx and BOT cancer. Methods: Treatment-naïve patients with stage III/IV (M0) hypopharynx or BOT cancer were randomly assigned to receive CRT alone (CRT arm: cisplatin 100 mg/m2 on D1 3-weekly, two times plus radiotherapy 68.4 Gy/30 fractions on weekdays) versus two 21-day cycles of IC with TPF (docetaxel & cisplatin 75 mg/m2 on D1, and fluorouracil 75 mg/m2 on D1-4) followed by the same CRT regimen (IC arm). The primary endpoint was progression-free survival (PFS). Results: This study closed early after enrollment of 36 patients (19 in the CRT arm, 17 in the IC arm). After a median follow-up of 47.2 months, there was no significant difference in PFS: the median PFS was 26.8 months for the CRT arm and was not reached for the IC arm (p = 0.13). However, the survival curves were widely separated with a plateau after 3 years, suggesting a potential survival benefit from IC: 3-year PFS rates were 45% and 68%, and 3-year overall survival rates were 56% and 86%, in the CRT and IC arms, respectively. Conclusions: This study failed to demonstrate that induction TPF chemotherapy improves survival in patients with BOT and hypopharynx cancer. However, it suggested a favorable outcome with IC to this population.

Hyperprogressive disease (HPD) is a distinct pattern of progression characterized by acceleration of tumor growth after treatment with anti-PD-1/PD-L1 Abs. However, the immunological characteristics have not been fully elucidated in patients with HPD. We prospectively recruited patients with metastatic non-small cell lung cancer treated with anti-PD-1/PD-L1 Abs between April 2015 and April 2018, and collected peripheral blood before treatment and 7-days post-treatment. HPD was defined as ≥2-fold increase in both tumor growth kinetics and tumor growth rate between pre-treatment and post-treatment.Peripheral blood mononuclear cells were analyzed by multi-color flow cytometry to phenotype the immune cells. Of 115 patients, 19 (16.5%) developed HPD, 52 experienced durable clinical benefit (DCB; partial response or stable disease ≥6 months), and 44 experienced non-hyperprogressive progression (NHPD). Patients with HPD had significantly lower progression-free survival (p<0.001) and overall survival (p<0.001). When peripheral blood immune cells were examined, the pre-treatment frequency of CD39+ cells among CD8+T cells was significantly higher in patients with HPD compared to those with NHPD, although it showed borderline significance to predict HPD. Other parameters regarding regulatory T cells or myeloid derived suppressor cells did not significantly differ among patient groups. Our findings suggest high pre-treatment frequency of CD39+ CD8+ T cells might be a characteristic of HPD. Further investigations in a larger cohort are needed to confirm our results and better delineate the immune landscape of HPD.

PURPOSE: The optimal cytotoxic regimens have not been established for patients with non-small cell lung cancer (NSCLC) who develop disease progression on first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). MATERIALS AND METHODS: We conducted a multi-center randomized phase II trial to compare the clinical outcomes between pemetrexed plus cisplatin combination therapy followed by maintenance pemetrexed (PC) and pemetrexed monotherapy (P) after failure of first-line EGFR-TKI. The primary objective was progression-free survival (PFS), and secondary objectives included overall response rate (ORR), overall survival (OS), health-related quality of life (HRQOL), and safety and toxicity profiles. RESULTS: A total of 96 patientswere randomized, and 91 patientswere treated at 14 centers in Korea. The ORR was 34.8% (16/46) for the PC arm and 17.8% (8/45) for the P arm (p=0.066). With 23.4 months of follow-up, the median PFS was 5.4 months in the PC arm and 6.4 months in the P arm (p=0.114). The median OS was 17.9 months and 15.7 months in PC and P arms, respectively (p=0.787). Adverse events ≥ grade 3 were reported in 12 patients (26.1%) in the PC arm and nine patients (20.0%) in the P arm (p=0.491). The overall time trends of HRQOL were not significantly different between the two arms. CONCLUSION: The outcomes of pemetrexed therapy in NSCLC patients with disease progression after firstline EGFR-TKI might not be improved by adding cisplatin.
Arm ; Carcinoma, Non-Small-Cell Lung ; Cisplatin ; Disease Progression ; Disease-Free Survival ; Epidermal Growth Factor ; Follow-Up Studies ; Humans ; Korea ; Lung Neoplasms ; Lung ; Pemetrexed ; Protein-Tyrosine Kinases ; Quality of Life ; Receptor, Epidermal Growth Factor ; Tyrosine

Trichloroethylene (TCE) is an organic solvent that is used for degreasing and removing impurities from metal parts. However, this solvent's characteristics and hypersensitivity can produce clinical patterns and laboratory data that mimic drug rash with eosinophilia and systemic symptoms (DRESS) syndrome. Thus, exposure confirmation is critical to making an accurate diagnosis. This is a case of TCE-induced hypersensitivity syndrome (TCE HS) in a 24-year-old Indonesian man who was working in an electro-plating business. He was admitted to a referral hospital after one month of working, and exhibited a fever with skin symptoms. He was administered immunosuppressive therapy based on an assumed diagnosis of DRESS syndrome, although he subsequently experienced cardiac arrest and did not respond to resuscitation. An investigation into his disease history confirmed that he was prescribed medications one week before he developed the skin disease, and had been periodically exposed to TCE for the previous 4 weeks. Based on these findings, it was believed that his clinical course was caused by TCE HS, rather than DRESS syndrome.
Commerce ; Diagnosis ; Drug Hypersensitivity Syndrome* ; Eosinophilia ; Exanthema ; Fever ; Heart Arrest ; Humans ; Hypersensitivity* ; Referral and Consultation ; Resuscitation ; Skin ; Skin Diseases ; Stevens-Johnson Syndrome ; Trichloroethylene* ; Young Adult

PURPOSE: The optimal perioperative treatment for resectable esophageal squamous cell carcinoma (ESCC) remains controversial. We evaluated the efficacy and safety of leucovorin and 5-fluorouracil (LV5FU2) and LV5FU2 plus oxaliplatin (FOLFOX) combination chemotherapies administered adjuvantly for curatively-resected, node-positive ESCC. MATERIALS AND METHODS: Patients with pathologically node-positive esophageal cancer after curative R0 resection were enrolled and randomly assigned to receive LV5FU2 or FOLFOX biweekly for up to eight cycles. The primary endpoint was disease-free survival (DFS). RESULTS: Between 2011 and 2015, 62 patients were randomized into the two treatment groups (32 in the LV5FU2 arm and 30 in the FOLFOX arm). The median age was 60 years and both groups had similar pathologic characteristics in tumor, nodal status, and location. Treatment completion rates were similarly high in both groups. The DFS rate at 12 months was 67% in the LV5FU2 group and 63% in the FOLFOX group with a hazard ratio of 1.3 (95% confidence interval [CI], 0.66 to 2.62). After a median follow-up period of 27 months, the median DFS was 29.6 months (95% CI, 4.9 to 54.2) in the LV5FU2 arm and 16.8 months (95% CI, 7.5 to 26.1) in the FOLFOX arm (p=0.428), respectively, while the median overall survival was not reached in either arm. Grade 3 or 4 neutropenia was more frequent in patients in the FOLFOX arm than the LV5FU2 arm (20.0% vs. 3.1%). CONCLUSION: The addition of oxaliplatin (FOLFOX) did not lead to better efficacy compared to LV5FU2 chemotherapy in an adjuvant setting in node-positive ESCC patients.
Arm ; Carcinoma, Squamous Cell* ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Drug Therapy ; Drug Therapy, Combination ; Epithelial Cells* ; Esophageal Neoplasms ; Fluorouracil ; Follow-Up Studies ; Humans ; Leucovorin ; Neutropenia