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The symposium on “Oncology Leadership in Asia” was held as part of the official program of the 42nd Annual Meeting of the Korean Cancer Association with International Cancer Conference. Given the increasing incidence of cancer in all countries and regions of Asia, regardless of developmental stage, and also in light of the recognized need for Asian countries to enhance collaboration in cancer prevention, research, treatment and follow-up, the symposium was held with the aim of bringing together oncology specialists from eight countries and regions in Asia to present the status in their own national context and discuss the key challenges and requirements in order to establish a greater Asian presence in the area of cancer control and research. The task of bringing together diverse countries and regions is made all the more urgent in that while Asia now accounts for more than half of all new cancer cases globally, clinical guidelines are based predominantly on practices adopted in Western countries, which may not be optimized for unique ethnic, pharmacogenomic and cultural characteristics in Asia. Recognizing the need for Asia to better gather information and data for the compilation of Asia-specific clinical guidelines, the participants discussed the current status in Asia in the national and regional contexts and identified future steps towards integrated and collaborative initiatives in Asia. A key outcome of the symposium was a proposal to combine and integrate the activities of existing pan-Asian societies, including the Asian Pacific Federation of Organizations for Cancer Research and Control (APFOCC) and Asian Clinical Oncology Society (ACOS). Further proposals included the expansion of pan-Asian society membership to include individuals and the essential need to encourage the participation of young researchers in order to ensure self-sustainability of cancer control efforts in the future.

The Japan National Committee for the Union for International Cancer Control (UICC) and UICC – Asia Regional Office organized an international session as part of the 74th Annual Meeting of the Japanese Cancer Association on the topic “What are the implications of sharing the concept of Universal Health Coverage for cancer in Asia?” Universal Health Coverage (UHC) is included in the United Nations’ Sustainable Development Goals and aims to ensure that all people can receive high‐quality medical services, are protected from public health risks, and are prevented from falling into poverty due to medical costs or loss of income arising from illness. The session discussed the growing cost of cancer and the challenges that this poses to the establishment and deployment of UHC in the Asian region, where countries face budgetary and other systemic constraints in tackling and controlling cancer. It was noted how sharing concepts on UHC will assist mutual learning among Asian countries and help in the formation of guidelines that can be adapted to national and regional realities. Presentations included a status report on UHC for cancer control in Thailand, and a report from the WHO Kobe Centre concerning prospects for collaborative research on UHC. Also discussed were the current status of cancer burden and control in China and Korea and Japan's progress in systemizing cost‐effectiveness evaluation. The final presentation highlighted the importance of gathering social and economic data across Asia in order to build a picture of commonalities and differences in the region., The Japan National Committee for the Union for International Cancer Control (UICC) and UICC‐Asia Regional Office (ARO) organized an international session as part of the official program of the 74th Annual Meeting of the Japanese Cancer Association to discuss the topic “What are the implications of sharing the concept of Universal Health Coverage for cancer in Asia?” The presenters and participants discussed the growing cost of cancer in the Asian region and the challenges that this poses to the establishment and deployment of UHC in the countries of Asia, all of which face budgetary and other systemic constraints in tackling and controlling cancer in the region.

PURPOSE Hypermethylation of the CpG island of p16(INK4a) occurs in a significant proportion of colorectal cancer (CRC). We aimed to investigate its predictive role in CRC patients treated with 5-fluorouracil, leucovorin, irinotecan (FOLFIRI), and cetuximab. MATERIALS AND METHODS Pyrosequencing was used to identify KRAS mutation and hypermethylation of 6 CpG island loci (p16, p14, MINT1, MINT2, MINT31, and hMLH1) in DNA extracted from formalin-fixed paraffin-embedded specimens. Logistic regression and Cox regression were performed for analysis of the relation between methylation status of CpG island methylator phenotype (CIMP) markers including p16 and clinical outcome. RESULTS Hypermethylation of the p16 gene was detected in 14 of 49 patients (28.6%) and showed significant association with KRAS mutation (Fisher exact, p=0.01) and CIMP positivity (Fisher exact, p=0.002). Patients with p16-unmethylated tumors had significantly longer time to progression (TTP; median, 9.0 months vs. 3.5 months; log-rank, p=0.001) and overall survival (median, 44.9 months vs. 16.4 months; log-rank, p=0.008) than those with p16-methylated tumors. Patients with both KRAS and p16 aberrancy (n=6) had markedly shortened TTP (median, 2.8 months) compared to those with either KRAS or p16 aberrancy (n=11; median, 8.6 months; p=0.021) or those with neither (n=32; median, 9.0 months; p < 0.0001). In multivariate analysis, KRAS mutation and p16 methylation showed independent association with shorter TTP (KRAS mutation: hazard ratio [HR], 3.21; p=0.017; p16 methylation: HR, 2.97; p=0.027). CONCLUSION Hypermethylation of p16 was predictive of clinical outcome in metastatic CRC patients treated with cetuximab and FOLFIRI, irrespective of KRAS mutation.

Purpose The purpose of this study was to evaluate the rate of pathologic complete response (pCR) in patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiation therapy (CRT) with leucovorin (FL) versus irinotecan/S-1 (IS). Methods and Materials Patients with resectable LARC (clinical stage T3/4, lymph node positive, or both) were randomly assigned to receive preoperative radiation (45-50.4 Gy in 25 to 28 daily fractions) and concomitant chemotherapy either with a bolus injection of FL (400 mg/m 2 /day 5-fluorouracil and 20 mg/m 2 /day leucovorin) for 3 consecutive days every 4 weeks for 2 cycles (FL group) or with 40 mg/m 2 irinotecan on days 1, 8, 15, 22, and 29, and 35 mg/m 2 S-1 twice on the day of irradiation (IS group). Curative surgery was performed approximately 4 to 8 weeks after the completion of CRT. The postoperative chemotherapy regimen was FL with a primary endpoint of a pCR rate evaluation. Results One hundred forty-two eligible patients were randomly assigned, and the median follow-up duration was 43.8 months (95% confidence interval, 40.8-46.8 months). One hundred thirty-three patients (93.7%) of 142 underwent total mesorectal excision; pCR was achieved in 11 (16.7%) of 66 patients in the FL group and 17 (25.8%) of 67 patients in the IS group ( P =.246). When good responders were defined as patients with Mandard grades 1 and 2, the rate of good responders was significantly higher in the IS group than in the FL group (54.6% vs 36.4%, respectively, P =.036). The preoperative rates of grade 3 and 4 toxicities were higher in the IS group (7.0%) than in the FL group (1.4%, P =.095). The 3-year disease-free survival was not significantly different between the 2 groups (79.7% vs 76.6%, respectively, P =.896). Conclusions IS-based preoperative CRT did not increase pCR rate, but it did increase acute toxicities compared with standard 5-FU treatment. Therefore, further investigation is needed.

We performed this study to define distinctive clinical features of leiomyosarcoma by assessing prognostic factors. Between 1988 and 2011, 129 leiomyosarcoma patients who underwent surgical resection with curative intent were retrospectively reviewed. Of the 129 leiomyosarcoma patients, the distribution of anatomic locations was: extremity (n = 25), pelvis (n = 40), thoracic cavity (n = 11), intra-abdomen (n = 19), retroperitoneum (n = 23), and head/neck (n = 11). We classified the anatomic locations into two categories as abdominal (intra-abdomen and retroperitoneum, n = 42) and extra-abdominal (extremity, pelvis, thoracic cavity, and head/neck, n = 87). Prognosis was worse for the abdominal group than for the extra-abdominal group (median DFS 2.9 9.0 years, P = 0.04). Similarly, overall survival (OS) was also significantly worse for abdominal group (P = 0.027). Independent prognostic factors for survival were primary site (P = 0.041, hazard ratio (HR) 1.7; 95 % CI 1.2–2.8), tumor size (P = 0.038, HR 1.9; 95 % CI 1.13–3.38), margin status (P = 0.019, HR 2.1; 95 % CI 1.13–3.88), and histology grade (P = 0.01, HR 3.59; 95 % CI 1.64–7.87). We identified four different risk groups with different survival outcome: group 1 (n = 8), no adverse factors; groups 2 (n = 37) and 3 (n = 61) with one and two adverse factors, and group 4 (n = 23) with 3 or 4 adverse factors. Primary site, tumor size, resection margin, and histology subtype were independently associated with survival outcome. A prognostic model for leiomyosarcoma patients revealed four distinct groups of patients with good prognostic discrimination.

On 16 June 2016, the Korean Cancer Association (KCA) and Union for International Cancer Control-Asia Regional Office (UICC-ARO) organized a joint symposium as part of the official program of the 42nd Annual Meeting of the Korean Cancer Association to discuss the topic 'Cross-boundary Cancer Studies: Cancer and Universal Health Coverage (UHC) in Asia.' Universal Health Coverage is included in the Sustainable Development Goals adopted by the United Nations as part of the 2030 Agenda for Sustainable Development. The objectives of UHC are to ensure that all people can receive high-quality medical services, are protected from public health risks, and are prevented from falling into poverty due to medical costs or loss of income arising from illness. The participants discussed the growing cost of cancer in the Asian region and the challenges that this poses to the establishment and deployment of UHC in the countries of Asia, all of which face budgetary and other systemic constraints in controlling cancer in the region. Representatives from Korea, Japan and Indonesia reported on the status of UHC in their countries and the challenges that are being faced, many of which are common to other countries in Asia. In addition to country-specific presentations about the progress of and challenges facing UHC, there were also presentations from WHO Kobe Centre concerning advancing UHC in non-communicable diseases and prospects for further collaboration and research on UHC. A presentation from the University of Tokyo also highlighted the need to focus on multidisciplinary studies in an age of globalization and digitization.

PURPOSE Colorectal cancer patients with liver-confined metastases are classified as stage IV, but their prognoses can differ from metastases at other sites. In this study, we suggest a novel method for risk stratification using clinically effective factors. MATERIALS AND METHODS Data on 566 consecutive patients with colorectal liver metastasis (CLM) between 1989 and 2010 were analyzed. This analysis was based on principal component analysis (PCA). RESULTS The survival rate was affected by carcinoembryonic antigen (CEA) level (p < 0.001; risk ratio, 1.90), distribution of liver metastasis (p=0.014; risk ratio, 1.46), and disease-free interval (DFI; p < 0.001; risk ratio, 1.98). When patients were divided into three groups according to PCA score using significantly affected factors, they showed significantly different survival patterns (p < 0.001). CONCLUSION The PCA scoring system based on CEA level, distribution of liver metastasis, and DFI may be useful for preoperatively determining prognoses in order to assist in clinical decisionmaking and designing future clinical trials for CLM treatment.

The Japan National Committee for the Union for International Cancer Control (UICC) and UICC-Asia Regional Office (ARO) organized an international session as part of the official program of the 72nd Annual Meeting of the Japanese Cancer Association to discuss the topic "What is cost-effectiveness in cancer treatment? " Healthcare economics are an international concern and a key issue for the UICC. The presenters and participants discussed the question of how limited medical resources can be best used to support life, which is a question that applies to both developing and industrialized countries, given that cancer treatment is putting medical systems under increasing strain. The emergence of advanced yet hugely expensive drugs has prompted discussion on methodologies for Health Technology Assessment (HTA) that seek to quantify cost and effect. The session benefited from the participation of various stakeholders, including representatives of industry, government and academia and three speakers from the Republic of Korea, an Asian country where discussion on HTA methodologies is already advanced. In addition, the session was joined by a representative of National Institute for Health and Care Excellence (NICE) of the United Kingdom, which has pioneered the concept of cost-effectiveness in a medical context. The aim of the session was to advance and deepen understanding of the issue of cost-effectiveness as viewed from medical care systems in different regions.

Background: Vascular soft-tissue sarcomas are a rare form of sarcoma. Malignant subtypes exhibit a variety of biological behaviors. We describe the clinicopathological characteristics and patient survival outcomes of malignant vascular soft-tissue sarcomas. Methods: We conducted a retrospective study on a cohort of 84 patients diagnosed with vascular tumors by histological examination at the Yonsei University College of Medicine between April 1987 and August 2011. The primary end point was overall survival (OS). Results: The angiosarcoma patients had a significantly shorter OS than the patients with other subtypes of sarcomas (59.0 and 142.7 months, respectively; p < 0.001). Upon multivariate analysis of survival in patients who underwent surgical resection, the following independent prognostic factors were identified: primary site (trunk, p = 0.001), age (older than 65 years, p < 0.001), pathology (angiosarcoma, p = 0.006) and R2 resection (p = 0.002). Conclusion: The independent prognostic factors for shorter survival are the trunk as the primary site, malignant angiosarcoma and age (>65 years). Complete excision should be attempted for providing a survival advantage in the patients with localized disease. In addition, bleeding episodes are much more frequent in patients with a poor survival outcome.

The Japan National Committee for the Union for International Cancer Control (UICC) and UICC‐Asia Regional Office (ARO) organized an international session as part of the official program of the 71st Annual Meeting of the Japanese Cancer Association to discuss the topic “Healthcare Economics: The Significance of the UN Summit non‐communicable diseases (NCDs) Political Declaration in Asia.” The presenters and participants discussed the growing cost of cancer in the Asian region and the challenges that are faced by the countries of Asia, all of which face budgetary and other systemic constraints in tackling and controlling cancer in the region. The session benefited from the participation of various stakeholders, including cancer researchers and representatives of the pharmaceutical industry. They discussed the significance of the UN Political Declaration on the prevention and control of NCDs (2011) as a means of boosting awareness of cancer in the Asian region and also addressed the ways in which stakeholders can cooperate to improve cancer control and treatment. Other issues that were covered included challenges relating to pharmaceutical trials in Asia and how to link knowledge and research outcomes. The session concluded with the recognition that with the onset of a super‐aged society in most countries in Asia and an increasing focus on quality of life rather than quantity of life, it is more important than ever for all stakeholders to continue to share information and promote policy dialogue on cancer control and treatment.

Adjuvant! Online (AOL) is a Web-accessible risk-assessment model that predicts the mortality and the benefits of adjuvant therapy for breast cancer. Using the Yonsei Tumor Registry database, patients with T1–3, N0–3, M0 breast cancer who were treated at the Yonsei Cancer Center between 1986 and 1999 were entered into AOL version 8.0 to calculate survival. The median age of the study population was 45 years (range, 23–76 years) and the median follow-up duration was 10.8 years (range, 0.1–25.9 years) for all 699 patients. AOL significantly overestimated overall survival (OS) (by 11.1 %, P

Aim To evaluate changing treatment patterns and survival outcomes of elderly patients (age 70 years or older) with resectable colon cancer over the past 15 years. Methods A total of 857 patients aged over 70 years who were managed for a resectable colon cancer between 1994 and 2010 were identified and their clinical variables were analyzed retrospectively. Results The patients’ median age was 74 years (range: 70–94 years). In all, 171 patients (20%) were stage I, 375 (43.8%) were stage II and 311 (36.3%) were stage III. Over 95% of all patients underwent surgery regardless of age or diagnosis year. In stage III colon cancer the proportion of patients who received adjuvant treatment increased the more recent the year of diagnosis (1994–2000, 47%; 2001–2005, 66%; 2006–2010, 70%; P = 0.017). According to analysis by age group, older patients were less likely to receive adjuvant chemotherapy in both stage II (more than 75 years, 47.3%; 70–74 years, 59.4%; P

Purpose Adjuvant chemotherapy has been known as a standard treatment for patients with resected colon cancer. However, in elderly colon cancer patients, the characteristics of patients are heterogeneous with regard to life expectancy and comorbidities. Thus, with regard to the effectiveness of adjuvant chemotherapy for colon cancer, it is difficult to extrapolate data of clinical trials from the younger into the older general population. Methods Data for 382 elderly colon cancer patients were analyzed: 217 in Stage II and 165 in Stage III. The efficacy of adjuvant chemotherapy was evaluated in elderly colon cancer patients after a match by the propensity score method. Results For matched patients with Stage II colon cancer, there was no significant efficacy of adjuvant chemotherapy in the risk of death during all follow-up periods (P-value, 0.06–0.37). Though there was a tendency that the adjuvant chemotherapy reduces the death rate during the follow-up periods, it was not statistically significant. In the case of Stage III, the adjuvant chemotherapy was significantly effective in matched patients for 5-year (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.30–0.90) and overall survival (HR, 0.56; 95% CI, 0.34–0.94). Conclusions Adjuvant chemotherapy for elderly patients with Stage II colon cancer is not effective, whereas elderly patients with Stage III with adjuvant chemotherapy appear to have a better survival rate in the general population. J. Surg. Oncol. 2013;107:613–618. © 2012 Wiley Periodicals, Inc.

Antimetabolic drugs bind to a specific enzyme and prevent normal metabolites from interacting with the enzymes, leading to inhibition of a specific metabolic pathway. Especially, the antimetabolic anticancer drugs interfere with DNA synthesis at multiple levels by inhibiting enzymes that utilize folic acid or synthesize the precursors of pyrimidine and purine, which are necessary for cell growth. In addition, some antimetabolites are directly incorporated into DNA, which inhibits DNA synthesis (Fig. 5.1). Therefore, these drugs are largely classified into folic acid derivatives that inhibit enzymes of folate pathway such as dihydrofolate reductase (DHFR), pyrimidine or purine derivatives that inhibit pyrimidine or purine synthesis, and direct inhibitors of DNA synthesis (Fig. 5.2).

The parallel development of life science and cancer treatment after the introduction of the cell theory in 1838 can be briefly summarized as shown in Fig. 11.1. In the mid-1850s, cancer entered the field of science after being designated as neoplasm, which is defined as a new mass of cells created from the division of tumor cells.

Schleiden and Schwann first reported the Cell Theory in 1838, and Remak and R. C. Virchow advocated this theory for cancer in the mid-1850s. They named cancer “neoplasm,” which was defined as a new mass of cells that emerges from abnormal proliferation of cells (Fig. 2.1). Thus, cancer was introduced into the field of science, was scientifically defined, and became an object of study.

Natural product anticancer drugs that are used clinically include compounds isolated from plants such as the vinca alkaloids, taxane/taxane analogues, podophyllotoxin derivatives, and camptothecin derivatives, as well as anticancer antibiotics isolated from various Streptomyces species such as anthracycline/anthracenedione, bleomycin, and actinomycin (Fig. 6.1). Vinca alkaloids and taxane/taxane analogues exhibit anticancer effects by inhibiting the microtubule function of spindle fibers, which is related to chromosome segregation, while podophyllotoxin derivatives, camptothecin derivatives, and other antibiotics cleave DNA bases, causing DNA damage through the suppression of topoisomerase I or II and the production of free radicals.

Advances in modern life sciences have primarily focused on cellular research because of the “Cell Theory” (Schleiden and Schwann 1838), which defines the cell as the basic unit of all organisms. Since cells are the common structural unit of a variety of organisms including animals and plants, it was hypothesized that complex life phenomena of multicellular organisms could be understood by studying individual cells. Molecular-level research began in 1953, when the double helix structure of DNA—the genetic material that transmits cellular characteristics to the next generation—was elucidated by Watson and Crick. Subsequently, advances in the understanding of the functions and mechanisms of cells were made rapidly.

From the middle of the 1960s, combination chemotherapy was at the center of chemotherapy for cancer. Following successful treatment of various hematologic malignancies through combination chemotherapy, significant effort was aimed at utilizing such treatments in patients with solid cancers. Research into solid cancer treatment using combination chemotherapy was a core component of anticancer research programs from 1970s, but in spite of long-term, large-scale clinical trials, revolutionary results did not emerge, and the progression of anticancer chemotherapy has gradually slowed since 1980. Ultimately, in 2003, it was determined that mega-dose combination chemotherapy combined with bone marrow transplant was not superior than conventional combination chemotherapy in advanced breast cancer, and it was widely believed that cytotoxic chemotherapy had reached its limit as a treatment for solid cancer. The failure of mega-dose cytotoxic chemotherapy as a treatment for solid cancers showed researchers that a deep biological understanding of the complexity and diversity of individual types of cancer was essential for more effective cancer treatment.

Cancer was not recognized as a major cause of death in western industrialized countries until the nineteenth century, but the cancer-related mortality increased rapidly after the decrease in lethal infectious diseases, such as tuberculosis and typhoid, following national efforts to improve hygiene and public health. The decrease in these diseases also rapidly increased the average life span, and since the twentieth century, cancer has become one of the leading causes of death, demonstrating that it is highly age-dependent. In the United States, life expectancy increased from 47 to 68 years in the first 50 years of the twentieth century, and cancer had been the second most common cause of death since 1933 [1]. Following this, cancer therapy has emerged as a matter of the national concern, and the F.D. Roosevelt administration enacted the world's first National Cancer Act in 1937, which sought the ways to overcome cancer at a national level by establishing the National Cancer Institute (NCI) that specialized in cancer research [2]. Later, European countries started making efforts to stop the spread of cancer, based on their national research institutions.

Paul Ehrlich, a pioneer in chemotherapy, experienced many failures while developing anticancer chemotherapy due to the indiscriminate toxicity of chemotherapy drugs. In 1915, based on his experience, he stressed on the importance of understanding the biological difference between normal cells and cancer cells for the development of a cancer-specific magic bullet. This suggestion was realized with the invention of targeted anticancer agents after decades of basic research in the field of cancer biology. Another example of an anticancer drug that was successfully developed after understanding the biological characteristics of a specific cancer is the hormonal anticancer drug.

Immunotherapeutic anticancer agents eliminate cancer cells by acting on the immune system and activating the immune response against cancer cells. This class of drugs includes cytokines such as INFγ and IL2, nonspecific immune stimulants BCG and levamisole, and recently developed anti-CTLA-4 monoclonal antibody ipilumumab.

Alkylating agents are the first chemotherapeutic anticancer agents developed, and account for the largest drug group among conventional cytotoxic chemotherapeutics. This class is largely divided into three subgroups: classical alkylating agents, nonclassical alkylating agents, and alkylating-like agents. Classical alkylating agents include nitrogen mustards, nitroso ureas, aziridines, and alkyl sulfonates. Nonclassical alkylating agents include hydrazine, triazene, and altretamines. In addition, the alkylating-like agent group, which functions by crosslinking with DNA similarly to alkylating agents, includes platinum compounds (Fig. 4.1).

To date, the Asia Cancer Forum has focused its efforts on creating a common concept for collaborative efforts in international cancer research with a focus on Asia, where cancer incidence is rising dramatically, and also sharing information and knowledge among cancer specialists about the importance of cancer as a global health agenda issue. The Eighth Asia Cancer Forum was held following the historic outcome of the High-level Meeting of the United Nations General Assembly on the Prevention and Control of Non-communicable Diseases held in New York in September 2011, at which cancer was duly recognized as a global health agenda issue. Despite this significant development, however, the issue of cancer, one of the most intractable of all non-communicable diseases, still faces a variety of challenges if it is to be addressed on the global level. The Eighth Asia Cancer Forum sought to address these various issues, seeking ways to capitalize on the outcomes of the UN Meeting and take global collaborative studies and alliances in the field of cancer further. It was recognized that one of the main challenges for the Asia Cancer Forum is to formulate a proposal that demonstrates how middle-income countries can provide a good level of care using only their own limited medical resources. Given that the Asia Cancer Forum is one of the organizations that can provide assistance in working to further boost awareness about cancer research and the situation relating to cancer in Asian countries, discussion also focused on how to concretize activities in the future.

We investigated the usefulness of a clinical risk scoring system (CRS) for guiding management and defining prognosis for patients with colorectal liver met"astases (CLM).We retrospectively analyzed data about the correlation between outcomes and Fong's CRS from 1989 to 2010 for patients treated for CLM at the Severance Hospital.Of 566 patients, 232 received adjuvant treatment after liver resection. Of these patients, 185 (81%) had a low CRS (0-2) and 47 (19%) had a high CRS (3-5). Stratification into high and low CRS allowed significant distinction between Kaplan-Meier curves for outcome. The 5-year survival rate was 88.5% and 11.5% among patients with a low and high CRS, respectively (P 0.001). Seventy patients with initially unresectable CLM underwent liver resection after tumor downsizing by induction chemotherapy. Shifting of the CRS from high to low (8 patients; 11.4%) improved disease-free survival and overall survival.High CRS is associated with worse survival after resection in resectable and unresectable disease. The CRS may be used for risk assessment when recommending oncological surgical timing in initially unresectable disease and treatment options for perioperative or adjuvant treatment in resectable disease.

The anti-vascular endothelial growth factor (VEGF) antibody bevacizumab has received considerable attention as a first-line treatment of advanced colorectal cancers. Difficulties associated with effectively monitoring the activity of this drug have prompted us to seek a pharmacodynamic marker suitable for defining the optimum biological dose and schedule of bevacizumab administration against colon cancer in early clinical trials.We evaluated inhibitory effects of bevacizumab on VEGF signaling and tumor growth in vitro and in vivo, and assessed phosphorylation of VEGF receptor 2 (VEGFR2) and downstream signaling in endothelial cells as pharmacodynamic markers using phospho-flow cytometry. We also validated markers in patients with metastatic colorectal cancer (mCRC) treated with bevacizumab-based chemotherapy.In in vitro studies, bevacizumab inhibited proliferation of human umbilical vein endothelial cells in association with reduced VEGF signaling. Notably, bevacizumab inhibited VEGF-induced phosphorylation of VEGFR-2, Akt, and extracellular signal-regulated kinase (ERK). In vivo, treatment with bevacizumab inhibited growth of xenografted tumors and attenuated VEGF-induced phosphorylation of Akt and ERK. The median percentages of VEGFR2 + pAkt + and VEGFR2 + pERK + cells, determined by phospho-flow cytometry, were approximately 3-fold higher in mCRC patients than in healthy controls. Bevacizumab treatment decreased VEGFR2 + pAkt + cells in 18 of 24 patients on day 3.Bevacizumab combined with chemotherapy decreased the number of VEGFR2 + pAkt + cells, reflecting impaired VEGFR2 signaling. Together, these data suggest that changes in the proportion of circulating VEGFR2 + pAkt + cells may be a potential pharmacodynamic marker of the efficacy of antiangiogenic agents, and could prove valuable in determining drug dosage and administration schedule.

PURPOSE: The combination of gemcitabine and docetaxel (GD) is used to effectively treat patients with soft tissue sarcoma (STS). It is widely considered that the conventional doses used are too high for long term use and many patients must discontinue GD treatment due to its toxicity. Therefore, to determine the appropriate dose meeting acceptable efficacy results, while minimizing toxic side effects, we treated patients with a weekly infusion of GD (weekly GD). MATERIALS AND METHODS: A total of 22 patients presenting a variety of STSs were treated at Yonsei Cancer Center. All patients had metastatic or recurrent cancer and had previously received doxorubicin and ifosfamide combination chemotherapy. In all cases, gemcitabine (1,000 mg/m(2)) and docetaxel (35 mg/m(2)) were administered intravenously on days 1 and 8 of a 21-day cycle. We retrospectively reviewed the medical records of these patients. RESULTS: The response rate was 4.5%, with one patient diagnosed with leiomyosarcoma having a partial response, and the disease control rate was 40.9%. The median progression-free survival (PFS) duration was 2.7 months and the PFS was correlated with the treatment response to a weekly GD. The median overall survival (OS) duration was 7.8 months and the OS was correlated with histology. There was no significant difference in OS between patients who received weekly GD as a 2nd line chemotherapy and those who received 3rd line or more. Treatment was generally well tolerated. CONCLUSION: Weekly GD was well tolerated and showed moderate efficacy, indicating that this could be a reasonable option as a salvage treatment for metastatic STS.

Purpose We evaluated the treatment efficacy including survival and recurrence, and factors associated with recurrence in osteosarcoma patients treated with preoperative chemotherapy, surgery, and adjuvant chemotherapy. Materials and methods Forty nine patients with osteosarcoma were treated with preoperative chemotherapy with intra-arterial cisplatin and adriamycin infusion for 3 cycles, followed by surgery. According to the pathologic response, if tumor was necrotized more than 90%, the same adjuvant chemotherapy was reintroduced for 3 cycles, and if the response was not enough, then the salvage regimen was introduced. Plain chest film and chest CT scan were taken monthly and every 3 months, respectively. When tumor recurred, the metastasectomy was performed whenever possible. Results Forty three patients were evaluable with amedian follow up of 53 months. Five-year disease-free and overallsurvival rate was 47.0% and 66.9%, respectively. The recurrence was observed in 22 patients (51.2%) with median time of 12.5 months. Baseline alkaline phosphatase (ALP) was the only significant factor for recurrence (p=0.03) and the patients with the possibility of metastasectomy recurrence showed higher post-relapse survival compared to other treatment modalities (26 momths vs 5~12 months). Conclusion These results indicates that pre- and postoperative chemotherapy with intra-arterial cisplatin and adriamycin infusion showed comparable treatment efficacy and acceptable toxicities.

Purpose: Peritoneal seeding is one of problems to be solved in gastrointestinal and ovarian cancers. Angiogenesis is the critical step for a dormancy tumor cluster to be an overt metastatic nodule. However, whether an anti-angiogenesis strategy is effective in the control of peritoneal metastases is still obscure. In this study, we evaluated whether endostatin, an endogenous angiogenesis inhibitor, suppresses peritoneal metastases. Materials and Methods: We transduced a human gastric cancer cell line, AGS and a murine renal cancer cell line, Renca, with the plasmid pEndoSTHB, which encodes a secretable form of murine endostatin. Endostatin expression was tested with western blotting, and the biological activity of the secreted endostatin was confirmed with in vitro endothelial cell growth inhibition. In the animal experiments, stable transfectants were injected intraperitoneally. Results: We demonstrated secretion of endostatin from two cell lines transduced with the plasmid pEndoSTHB. Conditioned media secreted from pEndoSTSB-transduced mammalian cells were shown to potently inhibit endothelial cell growth in vitro. We selected stable transfectants with similar in vitro growth rates of their parental cell lines. Significant tumor growth inhibition was observed in the endostatin-expressing Renca cells intraperitoneal injection group at days of 28, compared to the null transfectants intraperitoneal injection control group. Conclusion: These results support that peritoneal seeding is angiogenesis-dependant and an anti-angiogenesis strategy is a good way to control peritoneal metastases.

Purpose This study was performed to estimate the response rate and toxicity of a combination chemotherapy, which included infusional 5-Fluorouracil, Leucovorin and Docetaxel in the treatment of patients with an advanced gastric carcinoma. Materials and methods Twenty two advanced gastric cancer patients, with a bidimensionally measurable or an evaluable disease, were enrolled in this study. The patients received a 5-fluorouracil 1, 000 mg/m2 intravenous (IV) 24 hour infusion (Day 1~3), leucovorin 20 mg/m2 (Day 1~3) and docetaxel 75 mg/m2 intravenously (Day 2) every 3 weeks. Results The overall response rate was 45.0%. The median duration of response was 10.0 weeks (range: 4~24), the median time to response was 8 weeks (range: 8~20) the median time to progression was 30.0 weeks (95% CI: 16.3~43.2) and the median overall survival duration was 36.0 weeks (95% CI: 1.7~70.2). The median cumulative dose of 5-fluorouracil were 316.2 mg/m2/week and docetaxel was 23.9 mg/m2/week. WHO grade III, IV neutropenia, thromocytopenia and anemia occurred in 50.0%, 4.5% and 4.5% of patients, respectively. There were no occurrence of WHO grade III and IV nausea, vomiting, mucositis, conspitation, diarrhea, or neurotoxicity. Conclusion This chemotherapy regimen, including infusional 5-fluorouracil, leucovorin and docetaxel was an active agent against advanced gastric cancer patients, especially for previous chemotherapy naive patients.

Objective: To establish a comprehensive cancer treatment and prevention policy, data collection should be performed in a timely manner, and survival analysis needs to reflect changes in treatment strategy. Therefore, we introduced the concept of period analysis for gastric cancer, the most prevalent cancer in Korea. We estimated 5- and 10-year survival trend of gastric cancer, based on data from the Yonsei Cancer Center Tumor Registry between 1990 and 2004. Methods: We compared the differences in survival between cohort, complete and period analyses for two different periods, 1995‐99 and 2000‐04. Results: A total of 11 724 cases were included. The median age of cancer diagnosis gradually increased over time, and more patients were diagnosed with Stage I disease in recent years. In the basic comparison of three estimated analytic methods (cohort, complete and period), period analysis (45.8%) was most similar to the actual 5-year observed survival rate (48.5%), when compared with cohort (43.6%) and complete (44.8%) analyses. When we compared survival between different 10-year periods (1990‐99 and 1995‐2004), period analysis demonstrated a greater difference than complete analysis (9.0 versus 3.9%). Subgroup analysis indicated that the survival improvement was determined by period analysis, and it was more pronounced for the age group ,74 years and in Stages III‐IV patients. Conclusions: We observed that period analysis demonstrates the most similar results to the actual observed survival and is, therefore, a useful method to derive precise cancer survival in gastric cancer. This information is useful to understand survival differences that are influenced by changing treatment strategy.

Findings from the phase 3 FLEX study showed that the addition of cetuximab to cisplatin and vinorelbine significantly improved overall survival, compared with cisplatin and vinorelbine alone, in the first-line treatment of EGFR-expressing, advanced non-small-cell lung cancer (NSCLC). We investigated whether candidate biomarkers were predictive for the efficacy of chemotherapy plus cetuximab in this setting.Genomic DNA extracted from formalin-fixed paraffin-embedded (FFPE) tumour tissue of patients enrolled in the FLEX study was screened for KRAS codon 12 and 13 and EGFR kinase domain mutations with PCR-based assays. In FFPE tissue sections, EGFR copy number was assessed by dual-colour fluorescence in-situ hybridisation and PTEN expression by immunohistochemistry. Treatment outcome was investigated according to biomarker status in all available samples from patients in the intention-to-treat population. The primary endpoint in the FLEX study was overall survival. The FLEX study, which is ongoing but not recruiting participants, is registered with ClinicalTrials.gov, number NCT00148798.KRAS mutations were detected in 75 of 395 (19%) tumours and activating EGFR mutations in 64 of 436 (15%). EGFR copy number was scored as increased in 102 of 279 (37%) tumours and PTEN expression as negative in 107 of 303 (35%). Comparisons of treatment outcome between the two groups (chemotherapy plus cetuximab vs chemotherapy alone) according to biomarker status provided no indication that these biomarkers were of predictive value. Activating EGFR mutations were identified as indicators of good prognosis, with patients in both treatment groups whose tumours carried such mutations having improved survival compared with those whose tumours did not (chemotherapy plus cetuximab: median 17·5 months [95% CI 11·7-23·4] vs 8·5 months [7·1-10·8], hazard ratio [HR] 0·52 [0·32-0·84], p=0·0063; chemotherapy alone: 23·8 months [15·2-not reached] vs 10·0 months [8·7-11·0], HR 0·35 [0·21-0·59], p0·0001). Expression of PTEN seemed to be a potential indicator of good prognosis, with patients whose tumours expressed PTEN having improved survival compared with those whose tumours did not, although this finding was not significant (chemotherapy plus cetuximab: median 11·4 months [8·6-13·6] vs 6·8 months [5·9-12·7], HR 0·80 [0·55-1·16], p=0·24; chemotherapy alone: 11·0 months [9·2-12·6] vs 9·3 months [7·6-11·9], HR 0·77 [0·54-1·10], p=0·16).The efficacy of chemotherapy plus cetuximab in the first-line treatment of advanced NSCLC seems to be independent of each of the biomarkers assessed.Merck KGaA.

TSU-68 is a novel multiple tyrosine kinase inhibitor that inhibits VEGFR-2, FGF and PDGF receptors. We conducted a phase I study to evaluate the safety and pharmacokinetic of TSU-68 when used with S-1 and oxaliplatin (SOX) in metastatic colorectal cancer (mCRC) patients. Patients with mCRC were treated with TSU-68 200 mg (Level 1) or 400 mg (Level 2) b.i.d. daily, S-1 35 mg/m(2) b.i.d. on Days 1-14 and oxaliplatin 130 mg/m(2) i.v. on Day 1 repeatedly every 3 weeks. Of eleven patients enrolled, two patients were excluded from dose limiting toxicity (DLT) assessment. Six patients at Level 1 experienced no DLT. Of three patients at Level 2, two patients experienced DLTs (one patient: grade 3 hiccup and palmar-plantar erythrodysaesthesia syndrome, another one: grade 2 neutropenia which prevented the initiation of next cycle within 14 days). The maximal tolerated dose (MTD) and recommended dose (RD) of TSU-68 was 200 mg b.i.d. C(max) and AUC(0-t) of TSU-68 at Level 2 were higher than those at Level 1, but doubling the dose of TSU-68 increased C(max) and AUC(0-t) less than two-fold. There was no appreciable difference in the PK of S-1 components (FT, CDHP and Oxo), 5-FU and oxaliplatin-derived platinum between Levels 1 and 2. A significant decrease in PDGF after TSU-68 treatment was identified and it might serve as pharmacodynamic marker of TSU-68. Administration of TSU-68 in combination with SOX is generally well tolerated. The MTD and RD of TSU-68 in this study was 200 mg b.i.d. daily.

This forum has continued to discuss the inclusion of cancer on the global health agenda, and specifically the Millennium Development Goals. The seventh forum presented an overview of activities to date, supplemented by reports from Korea, local governments in Japan and representatives from the pharmaceutical industry. Discussion focused on how to engage in measures to tackle cancer prevention and achieve early detection and effective treatment, using limited resources. It was recognized that with non-communicable diseases gaining increasing attention in international dialogue, it is now of the utmost importance to share an accurate recognition of cancer research and treatment throughout Asia and the wider world. Participants concurred that cancer issues are decoupled from the development aid agenda and that cooperation should be advanced on the basis of international cooperation without recourse to governmental development aid.

BACKGROUND: The purpose of this study was to compare 2 weekly docetaxel-based regimens as first-line treatments for advanced gastric cancer and to investigate the expression of secreted protein acidic and rich in cysteine (SPARC) and its abilities to predict treatment-related clinical outcomes. METHODS: Patients were randomly selected to receive 3 weekly cycles of docetaxel (35 mg/m2 on days 1 and 8) plus S-1 (35 mg/m2 each twice daily on days 1-14) (DS), or docetaxel plus cisplatin (35 mg/m2 each on days 1 and 8) (DC). Endpoints included overall response rate (primary), survival, toxicity, and quality of life (secondary). SPARC expression in prechemotherapy specimens of primary gastric tumors was evaluated via immunohistochemical analysis. RESULTS: Eighty patients were enrolled in the study. Confirmed overall response rates were 46% (95% confidence interval, 30%-62%) for DS and 24% (95% confidence interval, 11%-38%) for DC via intent-to-treat analysis. Median progression-free survival was 7.3 and 4.9 months and overall survival was 16.0 and 8.3 months for DS and DC, respectively. The most common grade ≥3 toxicity was neutropenia. Grade ≥3 mucositis (18%) and hand-foot syndrome (8%) were the toxicities most associated with DS, whereas anorexia (20%) and lethargy (20%) were more common with DC. High SPARC expression was related to early progression (hazard ratio, 3.67; P = .042) and poor overall survival (hazard ratio, 2.01; P = .010) in docetaxel chemotherapy on multivariate analysis. CONCLUSIONS: The outcomes in this study favored DS over DC for further phase 3 study. The findings suggest that split-dose weekly docetaxel alleviates hematological toxicity without compromising efficacy, and that SPARC expression may help individualize therapy in advanced gastric cancer. Cancer 2011. © 2010 American Cancer Society.

Background and purpose The aim of this study is to evaluate the efficacy and safety of preoperative radiation therapy combined with S-1 and irinotecan (SI) in LARC. Materials and methods Patients were considered LARC if they had a T3/T4 lesion or node positive. Weekly doses of 40mg/m 2 irinotecan were intravenously administered once per week during weeks 1–5 of radiotherapy. S-1 (70mg/m 2 ) was given from Monday to Friday in all weeks of radiotherapy. 3-D conformal radiotherapy was given at daily fractions of 1.8Gy for 5days for a total dose of 50.4 (45+5.4)Gy. Surgery was performed 4–6weeks following the completion of chemoradiation. Results Between June 2006 and November 2007, 43 pts were enrolled. The stage was: cT3 24 patients, cT4 6 patients; 28 patients were cN+. Forty-one patients completed the chemoradiation and 42 patients underwent operation: a low anterior resection was performed in 36 patients, a total colectomy in 1 patient, and an abdominal perineal resection in 5 patients. T downstaging was observed in 50%; 23 N+ patients became N− (55%). The complete pathological response was observed in 9 patients (21%). The 3-year locoregional failure rate, distant failure rate, disease-free survival, and overall survival were 9.5%, 18.6%, 72.1%, and 94.3%, respectively. Only three patients experienced G3 diarrhea; one had G3 sepsis and two had septic shock. Hematological toxicity (G3–G4) was observed in five patients. Conclusions This study demonstrated the efficacy of preoperative CRT with S-1 and irinotecan with 21% of complete response. However, prompt recognition and management of infection is needed to use it in patients with locally advanced rectal cancer.

A phase II study was conducted to evaluate S-1 monotherapy in previously untreated elderly or frail metastatic colorectal cancer patients. A total of 48 elderly (70-85 years old) and frail [Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2 and 65-69 years old] patients were eligible for first-line S-1 of 35 mg/m(2) given twice daily for 2 weeks followed by 1 week of rest. The overall response rate (ORR) for all patients was 19%. Similarly, the ORR for frail and elderly patients was 22% and 18%, respectively. Median progression-free survival (PFS) and overall survival (OS) for all patients were 3.9 months (95% CI, 3.0-4.8) and 11.3 months (95% CI, 7.4-15.2), respectively. For frail patients, PFS was 1.4 (95% CI, 0.8-2.0) vs. 4.3 months (95% CI, 3.0-5.4) for the elderly (P = 0.016). OS was significantly longer for elderly patients than for frail patients (13.1 months, 95% CI, 9.5-16.7) vs. (4.1 months, 95% CI, 3.2-5.0; P = 0.01). Toxicity was mild to moderate, as only 29% of patients experienced grade 3 toxicity. Grade 4 toxicity and febrile neutropenia did not occur; however, two frail patients died from grade 5 treatment-related infections. Generally, S-1 monotherapy was well-tolerated and efficacious in the elderly patient group, but not in the frail patient group. Considering performance status and co-morbidities in patients >70 years old, S-1 monotherapy may be a first-line therapeutic option for elderly mCRC patients.

It has been suggested that vasculogenesis by endothelial progenitor cells (EPC) as well as angiogenesis play an important role in the production of blood vessels in neoplasm. The present study was designed to isolate and characterize the EPC in gastric cancer patients as a tumor specific angiogenesis marker. The cells derived from CD34 positive PBMC presented with a cobblestone appearance at 28 days, revealing differentiation into endothelial cells. They were also positive to the LDL-uptake reaction, showing that they have biological endothelial cell functions. These cells demonstrated tube formation, showing their ability to participate in neovascularization. The cells derived from CD34 positive PBMC expressed CD133 and demonstrated telomerase activity, showing the stem cell character. In xenograft model, EPC derived from CD34 positive PBMC mobilized mainly into tumor area after being injected through tail vein. With isolation, ex vivo amplification and characterization of EPC from gastric cancer patients receiving chemotherapy, endothelial progenitor cells may be used as a candidate prognostic and predictive biomarker for cancer.

We evaluated the efficacy and tolerability of combined paclitaxel and ifosfamide in anthracycline- and docetaxel-pretreated metastatic breast cancer (MBC).Patients received paclitaxel (175 mg/m(2) i.v. in a 3-h infusion) on day 1 and ifosfamide (1.5 g/m(2) i.v. in a 15-min infusion) on days 1-3, every 3 weeks for a maximum of nine cycles. The tumor response was assessed every two cycles.We enrolled 34 patients with a median age of 50 years. Thirty patients had visceral metastases. Anthracycline- and docetaxel-based chemotherapy had previously been administered to 18/13 and 13/21 patients, respectively, in (neo)adjuvant/metastatic settings. Three patients had not previously received anthracycline due to abnormal cardiac functions. A total of 174 cycles of chemotherapy were delivered with a median of six cycles. The response rate under the intent-to-treat analysis was 23.5% (all partial responses) with a median response duration of 14 months. The disease control rate was 70.6%. The median progression-free and overall survival were 5.9 and 8.5 months, respectively. There was no apparent relationship between activity and prior docetaxel resistance. The incidence of grade III/IV neutropenia was 46.6% (81 of 174 cycles) with febrile neutropenia of only 1.7%. Major grade III/IV non-hematological toxicities included peripheral neuropathy (6 of 34 patients) and infection (4 of 34 patients). There were no treatment-related deaths.Paclitaxel combined with ifosfamide was effective and tolerable in anthracycline-/docetaxel-pretreated MBC. Overcoming docetaxel resistance by using paclitaxel in combination with ifosfamide needs to be addressed through further investigation.

We conducted a phase I trial of the antiangiogenic agent 6-O-(4-dimethylaminoethoxy) cinnamoyl fumagillol hemioxalate (CKD-732). Our aims were to determine the maximum tolerated dose (MTD), pharmacokinetics (PK), and safety profiles as well as identify the biologically active dose (BAD) from ex vivo pharmacodynamics (PD) and biomarkers of CKD-732. Using a dose escalation schedule, 19 patients with refractory solid tumors were enrolled at dose levels of CKD-732 ranging from 1 to 15 mg/m(2) given twice weekly for 2 weeks followed by a 1-week rest. No treatment-related deaths occurred in this study. Confusion and insomnia were dose-limiting toxicities (DLTs), and MTD was 15 mg/m(2). The area under the concentration-time curve (AUC) and maximum concentration (Cmax) increased dose dependently with increasing doses. The BAD was 5 mg/m(2) according to ex vivo PD. A decrement in soluble vascular endothelial growth factor receptor-3 (sVEGF-3) level was correlated with a reduction in tumor size (r = 0.54, P = 0.045). The results from this study showed an MTD of 15 mg/m(2) and a BAD of 5 mg/m(2).

We investigated the efficacy of cetuximab plus irinotecan, fluorouracil, and leucovorin (FOLFIRI) as first-line treatment for metastatic colorectal cancer and sought associations between the mutation status of the KRAS gene in tumors and clinical response to cetuximab.We randomly assigned patients with epidermal growth factor receptor-positive colorectal cancer with unresectable metastases to receive FOLFIRI either alone or in combination with cetuximab. The primary end point was progression-free survival.A total of 599 patients received cetuximab plus FOLFIRI, and 599 received FOLFIRI alone. The hazard ratio for progression-free survival in the cetuximab-FOLFIRI group as compared with the FOLFIRI group was 0.85 (95% confidence interval [CI], 0.72 to 0.99; P=0.048). There was no significant difference in the overall survival between the two treatment groups (hazard ratio, 0.93; 95% CI, 0.81 to 1.07; P=0.31). There was a significant interaction between treatment group and KRAS mutation status for tumor response (P=0.03) but not for progression-free survival (P=0.07) or overall survival (P=0.44). The hazard ratio for progression-free survival among patients with wild-type-KRAS tumors was 0.68 (95% CI, 0.50 to 0.94), in favor of the cetuximab-FOLFIRI group. The following grade 3 or 4 adverse events were more frequent with cetuximab plus FOLFIRI than with FOLFIRI alone: skin reactions (which were grade 3 only) (in 19.7% vs. 0.2% of patients, P0.001), infusion-related reactions (in 2.5% vs. 0%, P0.001), and diarrhea (in 15.7% vs. 10.5%, P=0.008).First-line treatment with cetuximab plus FOLFIRI, as compared with FOLFIRI alone, reduced the risk of progression of metastatic colorectal cancer. The benefit of cetuximab was limited to patients with KRAS wild-type tumors. (ClinicalTrials.gov number, NCT00154102.)

We investigated whether the level of bone marrow-derived progenitor cells and mature endothelial cells could be used as predictors of clinical outcome in patients receiving taxotere-based chemotherapy for advanced gastric cancer. Peripheral blood mononuclear cells were obtained from 49 gastric cancer patients who received taxotere combined with 5-FU and leucovorin and prophylactic G-CSF treatment. To categorize the cells, the cell markers CD34, vWF, P1H12, and CD31 were stained. Changes in these cells were examined before and after chemotherapy, and the clinical significance of these changes to response prediction and prognosis were investigated. Before the second cycle of chemotherapy, the number of CD34 + /vWF + and CD34 + cells was higher in non-responders as compared to the responders. Patients with ⩾6.2 CD34 + /vWF + cells/ml had a shorter progression free survival (3.7 months) as against patients with + /vWF + /ml (6.0 months, p = 0.076). Patients with ⩾5.8 CD34 + cells/ml had shorter progression free survival (4.0 months) than patients with + cells/ml (6.1 months, p = 0.046). In an ex vivo pharmacokinetic study, the maximum inhibition ( I max ) for HUVEC and YCC3 cells was 13.0 ± 6.6% and 74.0 ± 2.0%, respectively. The time to reach I max ( T max ) was 72 h in all HUVEC cells and 0.5 hours in YCC3 cells. We suggested that CD34 + /vWF + and CD34 + cells can be used as a biomarker for prediction and CD34 + cells for prognosis.

The purpose of this study is to investigate prognostic factors affecting oncologic outcomes in patients with locally recurrent rectal cancer and determine whether recurrence patterns influence curative resection of recurrent tumor.We examined 62 patients with isolated local recurrence following total mesorectal excision (TME) of the primary rectal cancer. Recurrence patterns were classified as central, anterior, posterior, lateral, and perineal with respect to the intra-pelvic tumor location. Prognostic factors affecting oncologic outcomes were analyzed, and the rate of curative resection was analyzed according to recurrence patterns.The mean follow-up period was 49.0 +/- 29.0 months, and the mean time to recurrence after TME was 27.9 +/- 23.3 months. Twenty-three patients underwent curative resection, and the remaining 39 patients received palliative treatment. Patients with a central recurrence had the highest rate of curative resection (p = 0.006). The overall 5-year survival rate was 13.9% and significantly higher in those treated with curative resection (35.1%; p = 0.0002). Multivariate analysis demonstrated that disease-free survival less than 1 year and curative resection of local recurrence were independent prognostic factors influencing 5-year survival.Patients with central recurrences have a high probability of curative resection. Disease-free survival less than 1 year and curative resection of local recurrence were independent prognostic factors affecting oncologic outcomes in patients with locally recurrent rectal cancer.

We evaluated the long-term natural history of gastric cancer after radical gastrectomy and adjuvant chemotherapy through a 15-year follow-up study at a single institute.Five hundred patients with advanced gastric adenocarcinoma who received radical gastrectomy and adjuvant chemotherapy were included in this long-term follow-up study. Patients were evaluated by imaging studies and upper gastrointestinal series or endoscopy every 6 months until the 10th year after surgery. Since then, the patients have been followed yearly in the same manner.The median follow-up period was 190.5 months. The recurrence rate in 5-year survivors was 10.8%. The dominant recurrence pattern was peritoneal carcinomatosis within 5 years and distant metastasis after 5 years post gastrectomy. Tumor stage was a clear-cut prognosticator within 5 years post gastrectomy, but was no longer informative in 5-10 years. At this period, only stage IV (IB-IIIB vs IVM0) was a significantly poor prognosticator. After 10 years, second primary cancer (seven cases) became as important an issue as recurrence of primary gastric cancer (six cases).In patients with gastric carcinoma treated with radical gastrectomy and adjuvant chemotherapy, late recurrence after 5 years post gastrectomy was not rare. Prognosticators were varied depending on the length of time after surgery. Tumor factors including stage were prognosticators within 5 years post gastrectomy, but tumor factors except stage IV had no prognostic value after 5 years. In the 5-10 years post gastrectomy, only stage IV (IB-IIIB vs IVM0) was a poor prognosticator. Also, after 10 years, there were no prognosticators.

The aim of this study was to investigate the efficacy and safety of the combination chemotherapy of paclitaxel, infusional 5-fluorouracil (5-FU) and leucovorin (FLT regimen) in advanced gastric cancer. The primary end point was the time to progression (TTP). Patients with evaluable disease with or without measurable lesions received 175 mg/m2 paclitaxel on day 1 followed by 20 mg/m2 leucovorin and 24-h infusion of 5-FU 1,000 mg/m2 (day 1-3) repeated every 3 weeks. Sixty patients were enrolled. The median TTP and overall survival duration were 13 and 60 weeks, respectively. One-year survival rate was 53.3%. Of the 50 patients with measurable lesion, the overall response rate was 31.7%. The most common grade 3–4 adverse event was neutropenia (61.7%). The FLT regimen showed an efficacy comparable to other regimens of cisplatin or anthracycline combinations with the advantage of remarkably low non-hematological toxicity. These data about the efficacy of this regimen need confirmation in a phase III trial.