• Journal of Chest Surgery
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• v.53 no.4
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• pp.160-167
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• 2020

Surgical resection is the mainstay of treatment for locally advanced esophageal cancer. Neoadjuvant therapy is recommended to improve survival, based on the results of several randomized trials and meta-analyses. However, controversy remains regarding how to combine surgery, radiotherapy, and chemotherapy. Moreover, in East Asia, the predominant histological type is esophageal squamous cell carcinoma, which has a different epidemiology and tumor biology from esophageal or gastroesophageal junctional adenocarcinoma. As such, the management of esophageal cancer in East Asia seems to be different from that in Western countries. Thus, this article reviews the current evidence on neoadjuvant therapy and considers the optimal combinations and ongoing strategies of multimodal therapy for esophageal squamous cell carcinoma.

• Journal of Chest Surgery
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• v.53 no.4
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• pp.168-171
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• 2020

Adjuvant therapy for completely resected esophageal squamous cell carcinoma is less commonly applied in clinical practice than neoadjuvant therapy, but it plays a substantial role in improving survival for esophageal cancer patients. This article presents a concise review of the evidence regarding adjuvant therapy for esophageal squamous cell carcinoma and future directions, particularly immunotherapy.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.2137-2140
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• 2016

Background: Gall bladder cancer (GBC) usually presents as unresectable or metastatic disease. We conducted a feasibility study to evaluate the effect of neoadjuvant therapy (NAT) on radiologic downstaging and resectability in unresectable GBC cases. Materials and Methods: Patients with locally advanced disease were treated with chemoradiotherapy [CTRT] ( external radiotherapy (45Gy) along with weekly concurrent cisplatin $35mg/m^2$ and 5-FU 500 mg) and those with positive paraaortic nodes were treated with neoadjuvant chemotherapy [NACT (cisplatin $25mg/m^2$ and gemcitabine $1gm/m^2$ day 1 and 8, 3 weekly for 3 cycles). Radiological assessment was according to RECIST criteria by evaluating downstaging of liver involvement and lymphadenopathy into complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). Results: A total of 40 patients were evaluated from January 2012 to December 2014 (CTRT=25, NACT=15). Pretreatment CT scans revealed involvement of hilum (19), liver infiltration (38), duodenum involvement (n=22), colon involvement (n=11), N1 involvement (n=11), N2 disease (n=8), paraaortic LN (n=15), and no lymphadenopathy (n=6). After neoadjuvant therapy, liver involvement showed CR in 11(30%), PR in 4 (10.5%), SD in 15 (39.4%) and lymph node involvement showed CR in 17 (50%), PR in 6 (17.6%), SD in 4 (11.7 %). Six patients (CTRT=2, NACT=4) with 66.6 % and 83% downstaging of liver and lymphnodes respectively underwent extended cholecystectomy. There was 16.6 % and 83.3% rates of histopathological CR of liver and lymph nodes. All resections were R0. Conclusions: Neoadjuvant therapy in unresectable gall bladder cancer results in a 15% resectability rate. This approach has a strong potential in achieving R0 and node negative disease. Radiologic downstaging (CR+PR) of liver involvement is 40.5% and lymphadenopathy is 67.5%. Nodal regression could serve as a predictor of response to neoadjuvant therapy.

• Journal of Chest Surgery
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• v.56 no.2
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• pp.67-74
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• 2023

Perioperative treatment with conventional cytotoxic chemotherapy for resectable non-small cell lung cancer (NSCLC) has proven clinical benefits in terms of achieving a higher overall survival (OS) rate. With its success in the palliative treatment of NSCLC, immune checkpoint blockade (ICB) has now become an essential component of treatment, even as neoadjuvant or adjuvant therapy in patients with operable NSCLC. Both pre- and post-surgery ICB applications have proven clinical efficacy in preventing disease recurrence. In addition, neoadjuvant ICB combined with cytotoxic chemotherapy has shown a significantly higher rate of pathologic regression of viable tumors compared with cytotoxic chemotherapy alone. To confirm this, an early signal of OS benefit has been shown in a selected population, with programmed death ligand 1 expression ≥50%. Furthermore, applying ICB both pre- and post-surgery enhances its clinical benefits, as is currently under evaluation in ongoing phase III trials. Simultaneously, as the number of available perioperative treatment options increases, the variables to be considered for making treatment decisions become more complex. Thus, the role of a multidisciplinary team-based treatment approach has not been fully emphasized. This review presents up-to-date pivotal data that lead to practical changes in managing resectable NSCLC. From the medical oncologist's perspective, it is time to dance with surgeons to decide on the sequence of systemic treatment, particularly the ICB-based approach, accompanying surgery for operable NSCLC.

• Journal of Digestive Cancer Research
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• v.2 no.2
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• pp.45-51
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• 2014

Gastric cancer is the second most common cancer and the third leading cause of cancer-related deaths in Korea. Many cases of gastric cancer are detected in the early stages on standard medical examinations; complete surgical and endoscopic resection is the most recommended treatment for early-stage gastric cancer. Nevertheless, many patients have already progressed to advanced gastric cancer (AGC) upon diagnosis, and the prognosis of such patients is very poor. Combination chemotherapy has been shown to produce a better quality of life (QOL) and to increase overall survival in AGC patients. However, approximately 50% of patients do not respond to the current first-line chemotherapy, while most patients who do respond eventually show disease progression. Accordingly, various second-line regimens have been investigated, and active salvage chemotherapy has been shown to improve the QOL and clinical outcomes in select AGS patients who can tolerate it. There is also an increasing need for neoadjuvant therapy for treating gastric cancer; therefore, various clinical trials have been set up to investigate different regimens. Neoadjuvant therapy is currently established as the standard treatment for locally AGC in Europe; it has contributed to lowering the nodal stages and has reduced overall mortality rates. Despite these benefits, many uncertainties remain. Therefore, further prospective, high quality randomized controlled trials for neoadjuvant therapies are needed to clarify their clinical benefits and to establish the most effective treatment strategies for AGC.

• Radiation Oncology Journal
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• v.17 no.4
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• pp.275-280
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• 1999

Purpose : To assess the feasibility and the toxicity of the neoadjuvant chemotherapy on the treatment of patients with locoregionally advanced nasopharyngeal carcinoma. Methods and Materials : We analyzed 77 previously untreated and histologically confirmed advanced stage nasopharyngeal carcinoma patients treated with neoadjuvant chemotherapy followed by radiation therapy at the Seoul National University Hospital between 1984 and 1996. The stage distribution was as follows : AJCC stage III-2, stage IV-75. Sixty-six patients received infusion of 5-FU (1000 mg/m$^2$, on Day 1$\~$5) and cisplatin (100 mg/m$^2$, on Day 1), eleven patients received infusion of 5-FU (1000 mg/m$^2$, on Day 1 $\~$5) and carboplatin (300 mg/m$^2$, on Day 1) as neoadjuvant chemotherapy Prior to radiation therapy. The median follow-up for surviving patients was 44 months. Results : The overall chemotherapy response rates were 87$\%$. The toxicities of chemotherapy were mild. Only 3 patients experienced Grade 3 toxicities (1 for cytopenia, 2 for nause/vomiting). The degree of radiation induced mucositis was not severe, and ten patients developed Grade 2 mucositis. The 5-year overall survival rates were 68$\%$ and the 5-year disease free survival rates were 65$\%$. The 5-year freedom from distant metastasis rates were 82$\%$ and 5-year locoregional control rates were 75$\%$. Conclusion : This single institution experience suggests that neoadjuvant chemotherapy improves overall survival and disease free survival for patients with advanced stage nasopharyngeal carcinoma without increase of toxicity.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2377-2381
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• 2013

A total of 285 patients with stage Ib2 and IIa2 cervical cancer were categorized into three groups, and received preoperative neoadjuvant chemotherapy combined with vaginal intracavitary irradiation, neoadjuvant chemotherapy alone or radiotherapy, respectively. The effective rate of 70.6 % in group 1 was much higher than 41.4% in group 2 (P=0.000) and 46.9 % in group 3 (P=0.000); The percentage of patients receiving postoperative adjuvant therapy was 44.1% in group 1, much lower than 67.8% in group 2 (P=0.001) and 64.6% in group 3 (P=0.004); The percentage of patients with no postoperative risk factor in group 1 was 52.0%, much higher than 32.2% in group 2 (P=0.006) and 35.4% in group 3 (P=0.019); The occurrence rate of surgery-related complications in groups 1, 2 and 3 were 29.4%, 28.7%, and 33.3%, respectively, with no statistical differences among the groups (P=0.981). Regarding preoperative neoadjuvant complications, none were obvious in group 3, while occurrence rates of myelosuppression in groups 1 and 2 were 89.1% and 86.6%, of nausea and vomitting were 78.4% and 78.2%, but without significant differences (all P>0.05). Among 166 patients who received postoperative adjuvant therapy in the three groups, the occurrence rates were: 65.4%, 64.3% and 61.1% respectively for myelosuppression; 42.3%, 38.1%, and 38.9% for nausea and vomiting; 9.6%, 9.5% and 9.7% for urocystitis; and 63.5%, 69.0% and 65.3% enteritis and rectitis. There were no statistically significant differences among them (all P>0.05). The five-year disease-free survival rates (DFS) in groups 1, 2, 3 were 78.3%, 75.1%, 80.9%, respectively; the five-year overall survival rates (OS) were 81.4%, 78.2%, and 81.1%, respectively. The five-year OS of 166 patients receiving postoperative in the three groups were 72.4%, 69.5%, and 71.8%, respectively, with no significant variation (all P>0.05). Although there were no differences among three groups in DFS and OS, preoperative neoadjuvant chemotherapy combined with intracavitary radiotherapy may increase the effective rate and the percentage of patients with no postoperative risk factors and decrease the percentage of patients receiving postoperative adjuvant therapy, thereby decreasing complications indirectly and increasing quality of life.

• Journal of Gastric Cancer
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• v.13 no.2
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• pp.73-78
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• 2013

Surgery is still considered to be the mainstay for the treatment of localized gastric cancer with negative margins (R0-resection) and an adequate lymph-node-dissection (D2-lymphadenectomy). Unfortunately, most cases of gastric cancer are only diagnosed at an advanced stage due to frequent recurrences after primary resection in curative intent. In order to improve prognosis after curative resection, in the recent past, patients with locally advanced tumors were subjected to a pre-, peri-, or postoperative treatment. Interestingly, postoperative chemotherapy has significantly improved survival after gastric resection in Asia, adjuvant radiochemotherapy is favored in North America and perioperative chemotherapy is considered as a treatment of choice in Europe indicating region specific approach towards the treatment. Recently there has also been growing evidence of positive outcomes of neoadjuvant radiochemotherapy on patient survival. In the present article, we discuss the concepts of neoadjuvant treatment approach and provide recommendations to surgeons based on current evidence.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6419-6425
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• 2013

Background: Neoadjuvant chemotherapy (NACT) is a treatment modality whereby chemotherapy is used as the initial treatment of HNSCC in patients presenting with advanced cancer that cannot be treated by other means. It leads to shrinkage of tumours to an operable size without significant compromise to essential oro-facial organs of the patients. The molecular mechanisms behind shrinkage due to NACT is not well elucidated. Materials and Methods: Eleven pairs of primary HNSCCs and adjacent normal epithelium, before and after chemotherapy were screened for cell proliferation and apoptosis. This was followed by immunohistochemical analysis of some cell cycle (LIMD1, RBSP3, CDC25A, CCND1, cMYC, RB, pRB), DNA repair (MLH1, p53) and apoptosis (BAX, BCL2) associated proteins in the same set of samples. Results: Significant decrease in proliferation index and increase in apoptotic index was observed in post-therapy tumors compared to pre-therapy. Increase in the RB/pRB ratio, along with higher expression of RBSP3 and LIMD1 and lower expression of cMYC were observed in post-therapy tumours, while CCND1 and CDC25A remained unchanged. While MLH1 remained unchanged, p53 showed higher expression in post-therapy tumors, indicating inhibition of cell proliferation and induction of apoptosis. Increase in the BAX/BCL2 ratio was observed in post-therapy tumours, indicating up-regulation of apoptosis in response to therapy. Conclusions: Thus, modulation of the G1/S cell cycle regulatory proteins and apoptosis associated proteins might play an important role in tumour shrinkage due to NACT.

• Korean Journal of Head & Neck Oncology
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• v.18 no.1
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• pp.41-45
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• 2002

Background and Objectives: To evaluate the efficacy of the neoadjuvant chemotherapy and radiation therapy in treatment of patients with advanced hypopharyngeal cancer, which is notorious for its poor prognosis and severe surgical morbidity with functional deficits. Materials and Methods: Medical records and radiologic findings of 107 patients with squamous cell carcinoma of the hypopharynx, Stage III or IV (AJCC, 1997), were retrospectively reviewed. Results: Neoadjuvant chemotherapy followed by radiation therapy showed 74% complete remission (CR) rate. The patients who did not show CR after chemotherapy had a high likelihood of treatment failure, even though they achieved CR following subsequent radiotherapy. Twenty-eight of 57 patients were able to preserve their larynges for more than three years by chemotherapy and radiation. Conclusions: This approach appeared to be as effective as radical surgery with postoperative radiation therapy without comprising of survival. To improve the cure rates, we need to develop better strategies to increase CR rates with chemotherapy and determine the best treatment option for patients who are partially or nonresponsive to chemotherapy.