Safety of osimertinib in adult patients with metastatic epidermal growth factor receptor T790M mutation?positive non?small cell lung cancer: Results from a Phase IV study in India

Background: A Phase IV, single?arm study was conducted to assess the safety of osimertinib in Indian patients with epidermal growth factor receptor (EGFR) T790M mutation?positive stage IV non?small cell lung cancer (NSCLC). Methods: Enrolled patients received 80 mg osimertinib for six cycles or until disease progression or unacceptable toxicity or withdrawal. Primary safety variables included treatment?emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events (AEs) leading to discontinuation/interruption/change (D/I/C) of drug dose, and AEs of special interest (AESIs). AEs were summarized by the percentage of patients experiencing at least one occurrence of each event. Results: Of the 60 enrolled patients (median age 58 [range: 34�] years; 51.7% women) at eight sites, nine patients were discontinued prematurely due to disease progression (n = 7) and death (n = 2); median (range) duration of treatment was 126 (1�4) days. Median age of patients was 58 (34�) years; 51.7% (n = 31) were women; 86.7% (n = 52) were nonsmokers; and most of them (98.3%) had adenocarcinoma. About 75% (n = 45) of patients experienced any of the TEAEs, with the most frequent being fatigue and creatine phosphokinase (CPK) increase (n = 6, 10% each). TEAEs in 11 (18.3%) patients were judged as study treatment related, with CPK increase being the most common (n = 4, 6.7%). TEAEs led to D/I/C of drug dose in eight (13.3%) patients, with one being study treatment related. Nine (15%) patients had AESIs of dyspnea (n = 6), chest pain (n = 2), and cardiorespiratory arrest (n = 1); two of them had a fatal outcome. One AESI (mild dyspnea) was considered study drug related. TEAEs of grade ?3 were reported in seven (11.7%) patients, including dyspnea in two (3.3%), followed by diarrhea, mucosal inflammation, cardiorespiratory arrest, and others (n = 1,1.7% each). None of the SAEs and fatal events were considered as study treatment related. Seven (11.7%) patients had abnormal electrocardiogram (ECG; not clinically significant) at the end of the study. Conclusion: Our study confirms the favorable safety profile of osimertinib without any new safety concerns in Indian patients with EGFR T790M mutation?positive stage IV NSCLC. ClinicalTrials.gov Identifier: NCT03853551 CTRI registration no. CTRI/2018/10/015941

Progress in conversion therapy for stage IV gastric cancer / 中华胃肠外科杂志

Gastric cancer is one of the most common malignancy in China. Most of the patients of gastric cancer treated clinically are in advanced stage. In the past years, with the progress of anti-cancer drug therapy, after the comprehensive treatment based on drugs therapy of inoperative stage IV gastric cancer, some cases can reduce the tumor stage and get the opportunity of radical operation. Some of the patients who underwent surgical treatment can get the chance of long-term survival. The results of REGATTA trial confirmed that palliative surgery plus chemotherapy could not improve the long-term survival of patients with stage IV gastric cancer. Neoadjuvant intraperitoneal plus intravenous chemotherapy can reduce the tumor stage of some cases of stage IV gastric cancer with peritoneal metastasis and receive surgical treatment, so as to gain the chance of long-term survival. Regimen of intraperitoneal hyperthermia chemotherapy combined with PHOENIX trial is expected to improve the conversion operation rate of gastric cancer with peritoneal metastasis. Paclitaxel-based three-drug chemotherapy can reduce the tumor stage of some inoperable advanced gastric cancer and obtain the opportunity of radical operation, improving the disease-free survival rate and overall survival rate of patients, thus has become the cornerstone of conversion therapy for stage IV gastric cancer. Antiangiogenic targeted drug apatinib combined with paclitaxel is safe and reliable, and can be used as an alternative for the conversion therapy of stage IV gastric cancer, which provides a new idea for cytotoxic drugs combined with targeted drugs. In the era of immunotherapy, the combined application and first-line application of immunosuppressive drugs has become a clinical consensus. For advanced Her-2 positive esophagogastric junction adenocarcinoma cases, the successful exploration of the four-drug combination of chemotherapy+ anti-Her-2 targeted drugs+ anti-PD1 monoclonal antibody combined with the first-line therapy has opened up a new era of transformational therapy for stage IV gastric cancer. Gastric cancer is a malignant tumor with high heterogeneity, the classification of stage IV gastric cancer represented by Yoshida classification is based on imaging, and a more reasonable classification method should be developed in combination with gene detection in the future. Based on this, an individualized and accurate conversion therapy plan is formulated, so as to effectively improve the long-term survival of patients with stage IV gastric cancer.

Comprehensive periodontal treatment in generalized stage IV, grade C periodontitis: a clinical case report / Tratamento periodontal abrangente em periodontite generalizada estágio IV, grau C: relato de caso clínico

Generalized stage IV, grade C periodontitis results in rapid bone destruction in the periodontium and can lead to early tooth loss. Scaling and root planing (SRP) complemented by systemic antibiotics, access surgery, regenerative techniques and implant placement are among the treatments used for patients with this condition. The aim of this article is to report a comprehensive periodontal treatment in a 23-year-old male who was referred to the periodontology department due to complaints of tooth mobility and gum infections diagnosed with generalized stage IV, grade C periodontitis according to the clinical, systemic, and family history features observed. Thorough non-surgical periodontal treatment consisting of scaling and root planing was provided, followed by a series of regenerative periodontal surgeries including guided tissue regeneration (GTR) and guided bone regeneration(GBR) to manage advanced bone defects. Six months after periodontal therapy, all implants were inserted using a one-stage approach and Six months later, they were restored with porcelain fused to metal crowns. During the one and two-year follow-ups, the teeth and implants did not show any signs of instability, attachment loss or bone loss. This case report shows that within the limitations of this study a successful outcome can be achieved with an early diagnosis and treatment involving elimination of infectious microorganisms and meticulous long-term maintenance combined with regenerative techniques and implant placement to restore the masticatory function and improve the quality of life for the patient. However further investigation and clinical studies are required to confirm these results (AU)

A periodontite generalizada estágio IV, grau C resulta em rápida destruição óssea do periodonto, podendo levar à perda dentária precoce. Raspagem e aplainamento radicular (SRP) complementada com antibióticos sistêmicos, acessos cirúrgicos, técnicas regenerativas e colocação de implantes estão entre os tratamentos usados para essa condição. O objetivo deste artigo é relatar o tratamento periodontal abrangente de um paciente de 23 anos, que foi encaminhado ao departamento de periodontia com queixas de mobilidade dentária e infecções gengivais, diagnosticado com periodontite generalizada estágio IV, grau C de acordo com as características clínicas, sistêmicas e de histórico familiar observadas. O tratamento periodontal não cirúrgico completo de raspagem e aplainamento radicular foi realizado, seguido por cirurgias periodontais regenerativas, incluindo regeneração tecidual guiada (GTR) e regeneração óssea guiada (GBR) para tratar defeitos ósseos avançados. Seis meses após a terapia periodontal, todos os implantes foram inseridos através de abordagem de estágio único e, seis meses depois, foram restaurados com porcelana fundida às coroas de metal. Durante os acompanhamentos de um e dois anos, os dentes e implantes não mostraram quaisquer sinais de instabilidade, perda de inserção ou perda óssea. Este relato mostra que, dentro das limitações deste estudo, um resultado bem-sucedido pode ser alcançado a partir de diagnóstico precoce e tratamento envolvendo a eliminação de microrganismos e manutenção meticulosa à longo prazo, combinada com técnicas regenerativas e colocação de implantes para restaurar a função mastigatória e melhorar a qualidade de vida do paciente. No entanto, mais investigações e estudos clínicos são necessários para confirmar esses resultados (AU)

Role of hypofractionated palliative radiotherapy in patients with stage four head-and-neck squamous cell carcinoma

Background: Large number of patients with head-and-neck cancer presents with factors such as advanced disease, poor general condition, and associated comorbidities due to which radical treatment is not recommended in these patients. In this scenario, the aim of the present study is to assess the role and feasibility of hypofractionated palliative radiotherapy in these patients. Subjects and Methods: This study was conducted on patients with histopathologically proven cases of squamous cell carcinoma of the head-and-neck region who were surgically unresectable. The quality of life (QOL) was assessed before and after 1 month of radiotherapy using University of Washington Quality of Life questionnaire version 4. All patients received 40 Gy in 10 fractions, twice weekly by two lateral fields covering primary and secondary disease. Response evaluation criteria in solid tumor criteria were used to assess the tumor response. Toxicity was assessed weekly using radiation therapy oncology group criteria. Results: A total of 50 patients were enrolled in this study, out of which 46 completed the planned treatment of 40 Gy in 10 fractions. Common complaints were distressing pain at the primary site (42%), neck swelling (30%), difficult in swallowing (18%), and change in voice (10%). Statistically significant improvements were observed in overall QOL (26.9 ± 9.63 to 55.65 ± 19.28) and none of them experienced Grade IV mucositis or skin toxicity. Good objective response was seen in 82.6% and 84.7% of patients at primary and nodal sites, respectively. Conclusions: This hypofractionated palliative radiotherapy regimen is a good treatment option in patients with Stage IV head-and-neck cancer, who are not fit for treatment with curative intent.

Stage IV Burkitt Lymphoma Presenting with Eyelid Swelling

@#Burkitt lymphoma is a rare and aggressive tumour which predominantly affects children. We report a case of Stage IV Burkitt lymphoma (non-endemic type) in a 5-year-old immunocompetent Malay child who initially presented with left upper eyelid swelling. Clinical examination revealed a soft solid swelling over the left upper lid, extending temporally up to the lacrimal gland. Computed tomography (CT) scan showed a homogenous mass of soft tissue density with intracranial and left orbital involvement. Incisional biopsy of the mass revealed histological changes suggestive of B lymphoblastic lymphoma or leukemia. She was treated with 6 cycles of chemotherapy. Post chemotherapy, the left temporal and upper eye lid swelling subsided. Clinicians need to be on alert when encountering children with eyelid swelling, as this could be an initial presenting feature of Burkitt lymphoma without other systemic symptoms. A delay in diagnosis can lead to aggressive orbital involvement followed by permanent visual loss.

Factores pronósticos para la supervivencia de pacientes con cáncer de ovario estadio IV / Prognostic factors for survival of patients with stage IV ovary cancer

El objetivo de la investigación fue identificar los factores pronósticos para la supervivencia de pacientes con cáncer de ovario estadio IV. Se realizó un estudio retrospectivo en el que se incluyeron todas las pacientes con diagnóstico de cáncer de ovario estadio IV, tratadas en el Hospital Central Dr. Urquinaona, Maracaibo, Venezuela, en el periodo entre enero de 2007 y junio de 2016. Los datos analizados fueron edad, variante histológica de la tumoración, sitio de la metástasis, concentraciones de CA-125 preoperatorios, resultado de la cirugía de citorreducción y respuesta a quimioterapia. Se utilizó el modelo de regresión de riesgos proporcionales de Cox para identificar variables independientes asociadas con la supervivencia. Resultados: Se identificaron 171 pacientes con cáncer de ovario estadio IV. El sitio más común de la enfermedad metastásica a distancia fue el derrame pleural maligno (40,9 %). En 59,1 % de las pacientes se logró una cirugía de citorreducción óptima. El análisis multivariante demostró que el resultado óptimo de la cirugía de citorreducción fue un predictor pronóstico independiente de supervivencia Se concluye que la cirugía de citorreducción con resultados óptimos es el factor pronóstico más importante para la supervivencia en pacientes con cáncer de ovario estadio IV.

The objective of the research was to identify prognostic factors for the survival of patients with stage IV ovarian cancer. A retrospective study was conducted in which all the patients diagnosed with stage IV ovarian cancer, treated at the Hospital Central Dr. Urquinaona, Maracaibo, Venezuela in the period between January 2007 and June 2016. Data analyzed were age, the histological variant of the tumor, site of metastasis, preoperative CA-125 concentrations, result of cytoreduction surgery and Response to chemotherapy. The Cox proportional hazards regression model was used to identify independent variables associated with survival. One hundred and seventy one patients with stage IV ovarian cancer were identified. The most common site of distant metastatic disease was malignant pleural effusion (40,9 %). Optimal cytoreduction surgery was achieved in 59,1% of the patients. Multivariate analysis showed that the optimal outcome of cytoreduction surgery was an independent predictor of survival (p = 0.028, hazard ratio 0.191; 95 % confidence interval, 0.043- 0.840). It is conclude that optimal cytoreduction surgery is the most important prognostic factor for survival in patients with stage IV ovarian cancer.

Terapia de conversión en cáncer gástrico estadio IV: a propósito de un caso / Case Report of Conversion Therapy in Stage IV Gastric Cancer

Resumen Se reporta el caso de una paciente de 47 años, con diagnóstico inicial de un tumor de Krukenberg por una lesión anexial de 10 cm de diámetro y una lesión corporal gástrica de 3 cm. La biopsia mostró un adenocarcinoma pobremente diferenciado con células en anillo de sello. Una laparoscopia inicial mostró un índice de carcinomatosis peritoneal (ICP) de 24, por lo cual se le indica a la paciente quimioterapia con intención paliativa (cisplatino y capecitabina). Con mejoría clínica importante, respuesta adecuada y favorable a la quimioterapia, la paciente se remitió a una salpingo-ooforectomía bilateral. Continúa con quimioterapia evidenciándose mejoría de las imágenes tomográficas y una excelente respuesta clínica. Por este motivo, se decide en conjunto con la familia llevarla a cirugía. Se le practica una gastrectomía total con linfadenectomía D2 con intención curativa. La paciente recibe quimioterapia con capecitabina y cisplatino por 3 meses más, hasta cuando se evidencia compromiso ganglionar paraaórtico, por lo que es necesario reiniciar la quimioterapia con un nuevo esquema, entonces se le formula irinotecán. La paciente completa 22 meses desde el diagnóstico inicial, la condición clínica es muy buena y está asintomática.

Abstract We report the case of a 47-year-old patient initially diagnosed with a Krukenberg tumor, an adnexal lesion 10 cm in diameter and a 3 cm lesion in the gastric corpus. A biopsy showed a poorly differentiated adenocarcinoma with signet ring cells. Initial laparoscopy showed an index of peritoneal carcinomatosis of 24 which indicated chemotherapy with palliative intent (cisplatin and capecitabine). The patient improved significantly and underwent a total hysterectomy with salpingo-oophorectomy. Chemotherapy continued with excellent clinical response as evidenced in CT scans. Together with the patient's family, it was decided that she should undergo surgery. A total gastrectomy with D2 lymphadenectomy with curative intent was performed. The patient continued to receive capecitabine and cisplatin for three more months until para-aortic lymph node involvement was demonstrated and it became necessary to restart chemotherapy with a new scheme using iriniotecan. The patient has completed 22 months after the initial diagnosis in very good and clinical condition without symptoms.

Clinical efficacy and safety of randomized phase 2 trial of pemetrexed-cisplatin or docetaxel-cisplatin plus thoracic intensity-modulated radiation therapy in patients with stage IV lung adenocarcinoma / 中华放射肿瘤学杂志

Objective To evaluate the clinical efficacy and toxicity of concurrent pemetrexed-cisplatin (PP) or docetaxel-cisplatin (DP) with intensity-modulated radiation therapy (IMRT) in patients with stageⅠV lung adenocarcinoma. Methods Stage IV lung adenocarcinoma patients with unknown EGFR mutation status or wild-type admitted to Guizhou Cancer Hospital from 2011 to 2016 were randomly assigned into the PP (n=50) and DP groups (n=51).All patients received concurrent IMRT of the chest at a prescription dose of 60-70 Gy. Primary endpoint was 1-year survival rate, and secondary endpoint was acute toxicity. Results The overall response rate was 68. 0％ and 72. 5％ in the PP and DP groups (χ2=0. 250, P=0. 617) . The median survival time was 19. 6 months ( 95％CI 13. 9-25. 3) versus 12. 1 months ( 95％CI 10. 7-13. 5) in the PP and DP groups. The 1-, 2-and 3-year overall survival rates were 72. 0％ versus 52. 9％, 28. 0％ versus 17. 6％, and 16. 0％ versus 13. 7％, respectively in the PP and DP groups ( P=0. 049) . In the PP and DP groups, the incidence of grade 3-4 leukopenia was declined by 48％ and 63％( P=0. 098) , and the incidence of grade 3-4 neutropenia was decreased by 34％ and 65％( P=0. 002) , the incidence of grade 3-4 anemia was reduced by 38％ and 10％(P=0. 024), and the incidence of grade 3-4 thrombocytopenia was declined by 40％ and 14％( P=0. 003) . The incidence rate of grade 2 pneumonitis ( P=0. 625) and grade 3 esophagitis ( P=0. 484) were similar in both groups. No patients experienced ≥grade 3 pneumonitis or ≥ grade 4 radiation esophagitis. Conclusions Pemetrexed-cisplatin combined with chemoradiotherapy yields higher clinical efficacy compared with docetaxel-cisplatin plus concurrent chemoradiation in the treatment of stageⅠV lung adenocarcinoma. The incidence of radiation pneumonitis and esophagitis is similar. The incidence and severity of hematological toxicity does not significantly differ between two groups.Treatment-related toxicity is tolerable in both groups. Clinical Trial Registration Chinese Clinical Trial Registry ( ChiCTR-TRC-13004184) .

Effect of excision extension of primary tumors on local control and survival of stage IV neuroblastoma / 中国肿瘤临床

Objective: To investigate the effect of gross total resection on the local control and survival of patients with stage IV neuroblastoma (NB) and analyze the extent of surgical resection of primary tumors that affects patient survival. Methods: A total of 96 patients with stage Ⅳ NB who were admitted to the Sun Yat-Sen University Cancer Center between January 2000 and December 2011 were analyzed. The patients were treated with combined-modality therapy, including chemotherapy, surgery, and/or radiotherapy. The patients were divided according to the extent of surgical resection of primary tumor into the following groups: group A, biopsy or tumor removal of less than 50% of the primary lesion; group B, incomplete resection of more than 50% but less than 90% of the lesion; group C, removal of more than 90% of the lesion; and group D, complete resection with or without macroscopic residual tumors. The survival rates of each group were analyzed. Results: The median age of the 96 patients was 4.4 years, ranging from 1.2-18.8 years. The overall 3-year progression-free survival (PFS) and overall survival (OS) of the total patients were 32.8% and 36.7%, respectively. A total of 24 cases were assigned in group A, 10 in group B, 23 in group C, and 39 in group D. Subgroup analysis revealed that the 3-year PFS rate was 17.5% for group A, 20.0% for group B, 45.1% for group C, and 40.5% for group D. The PFS rates were not statistically significant-ly different between groups A and B (P=0.352) and between groups C and D (P = 0.792). However, the OS was higher in groups C and D than that in groups A and B. The 3-year PFS rates were 42.2% and 17.8% for groups C and D (P<0.001), respectively. Conclu-sion: Resection extension of more than 90% of the primary tumor combined with chemotherapy and (or) radiation therapy can improve the survival of patients with stage Ⅳ NB. However, this treatment modality does not affect the treatment outcomes for minimal gross tu-mor residuals.

Factors Affecting Long Term Survival after Gastrectomy for Stage IV Gastric Cancer

PURPOSE: The prognosis of stage IV gastric cancer is poor, but some patients with stage IV gastric cancer survive for more than 5 years. We investigated the prognostic factors of the stage IV gastric cancer in the patients with survival for more than 5 years after resection of the primary lesion. METHODS: We retrospectively analyzed 194 patients that underwent resection of stage IV gastric cancer from January 1997 to June 2000 in our hospital. We investigated clinicopathological characteristics between patients surviving 5 years or more group (n=17) and less than 5 years group (n=177) with chi-square and T-test. We used univariate analysis with Kaplan-Meier method and Log-rank test, and multivariate analysis with Cox proportional hazard model to investigate prognositic factors for survival rate about each characteristic. RESULTS: In clinicopathological characteristics between the two groups, we observed statistical significance in regard to macroscopic findings (P=0.035), but not in the others. Curative resection (P=0.001) and intravenous chemotherapy (P=0.012) had statistically significant influence on 5-year survival curve. Multivariate analysis showed that curative resection was a significant factor for long-term survival rates (P=0.005), but chemotherapy and macroscopic type had no effect on survival rate. CONCLUSION: Although this study has the limitation of a retrospective study and total patient number in the 5-year survival group, curative resection may be important, as a prognostic factor, and active treatments should be performed for stage IV gastric cancer.

The Impact of Primary Tumor Resection on the Survival of Patients with Stage IV Breast Cancer / 한국유방암학회지

PURPOSE: The main treatment for stage IV breast cancer is currently systemic therapy. Surgical resection of the primary tumor is usually done for treating the tumor-related complications. Recent studies have suggested that surgery may improve the long-term survival of stage IV breast cancer patients. We evaluated the impact of the primary surgical resection site on the survival of stage IV breast cancer patients. METHODS: We reviewed the records of the stage IV breast cancer patients who were treated at Seoul University Hospital between April 1992 and December 2007. The tumor and clinical characteristics, the type of treatments and the overall survival were compared between the surgically versus nonsurgically treated patients. RESULTS: Of the 198 identified patients, 110 (55.8%) received surgical excision of their primary tumor and 88 (44.2%) did not. The mean survival was 67 months vs. 42 months for the surgically treated patients vs. the patients without surgery, respectively (p=0.0287). On a multivariate analysis with using the Cox model and after adjusting for the estrogen receptor status, visceral metastases, the number of metastatic sites and trastuzumab treatment, surgery was an independent factor for improved survival (hazard ratio, 0.55; 95% confidence interval, 0.31-0.97; p=0.041). CONCLUSION: Surgical resection of the primary tumor in stage IV breast cancer patients was independently associated with improved survival. Randomized prospective trials are needed to firmly recommend surgical resection of the primary tumor in stage IV breast cancer patients.

The Impact of Primary Tumor Resection on the Survival of Patients with Stage IV Breast Cancer / 한국유방암학회지

PURPOSE: The main treatment for stage IV breast cancer is currently systemic therapy. Surgical resection of the primary tumor is usually done for treating the tumor-related complications. Recent studies have suggested that surgery may improve the long-term survival of stage IV breast cancer patients. We evaluated the impact of the primary surgical resection site on the survival of stage IV breast cancer patients. METHODS: We reviewed the records of the stage IV breast cancer patients who were treated at Seoul University Hospital between April 1992 and December 2007. The tumor and clinical characteristics, the type of treatments and the overall survival were compared between the surgically versus nonsurgically treated patients. RESULTS: Of the 198 identified patients, 110 (55.8%) received surgical excision of their primary tumor and 88 (44.2%) did not. The mean survival was 67 months vs. 42 months for the surgically treated patients vs. the patients without surgery, respectively (p=0.0287). On a multivariate analysis with using the Cox model and after adjusting for the estrogen receptor status, visceral metastases, the number of metastatic sites and trastuzumab treatment, surgery was an independent factor for improved survival (hazard ratio, 0.55; 95% confidence interval, 0.31-0.97; p=0.041). CONCLUSION: Surgical resection of the primary tumor in stage IV breast cancer patients was independently associated with improved survival. Randomized prospective trials are needed to firmly recommend surgical resection of the primary tumor in stage IV breast cancer patients.

The Significance of Prophylactic Gastrojejunostomy for Patients with Unresectable Stage IV Gastric Cancer

PURPOSE: The aim of this study was to evaluate the significance of palliative gastrojejunostomy for treating patients with unresectable stage IV gastric cancer, and as compared with laparotomy for treating patients with incurable gastric cancer. MATERIALS AND METHODS: We retrospectively studied 167 patients who could not undergo resection without obstruction at Korea University Hospital from 1984 to 2007. They were classified into two groups, one that underwent palliative gastrojejnostomy (the bypass group, n=62) and one that underwent explo-laparotomy (the O&C group, n=105), and the clinical data and operative outcomes were compared according to the groups. RESULTS: For the clinical characteristics, there were no differences of age, gender and liver metastasis between the bypass group and the explo-laparotomy group, but there was a significant different for the presence of peritoneal metastasis (P=0.001). There was no difference between two groups for the postoperative mortality and morbidity. For the postoperative outcomes, the duration of the hospital stay (29.25 vs 16.67) and the frequency of re-admission were not different, but the median overall survival (4.3 months vs. 3.4 months, respectively) was significantly different. By multivariate analysis, the presence of peritoneal metastasis was identified as the independent prognostic factor for incurable gastric cancer. CONCLUSION: A prophylactic bypass procedure is not effective for improving the quality of life and prolonging the life expectancy of unresectable stage IV gastric cancer patients without obstruction.

The Effect of Adjuvant Chemotherapy on Stage IV (T4N1-3M0 and T1-3N3M0) Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The optimal chemotherapeutic strategy for gastric cancer patients has not been determined, especially with respect to stage and the curability of gastric cancer. The aim of this study was to evaluate the results of adjuvant chemotherapy on stage IV (T4N1-3M0 and T1-3N3M0) gastric cancer after curative gastrectomy between a chemotherapy (CTX) group and non-chemotherapy (non-CTX) group. MATERIALS AND METHODS: Among 1,760 patients who underwent gastric surgery by 1 surgeon in a single institution, 162 stage IV gastric cancer patients with curative gastrectomy were analyzed retrospectively, excluding patients with TanyNanyM1. One hundred twenty-five patients who received different chemotherapeutic regimens were compared to 37 patients who did not receive chemotherapy for reasons of old age or according to their expressed desire. RESULTS: The clinicopathologic factors which showed a clinically significant difference between the two groups were age and histology, which were not associated with patient survival. The CTX group was younger, and had a larger proportion of undifferentiated gastric cancers than the non-CTX group. The mode of treatment failure revealed no significant difference between the CTX and non-CTX groups. The 1, 3, and 5-year disease-free survival and the 1, 3, and 5-year disease-specific survival of the CTX group were 63.9%, 38.4%, and 32.0%, and 85.4%, 52.3%, and 39.6%, respectively, which were more favorable than the non-CTX group (p=0.015 and p=0.001, respectively). Postoperative adjuvant CTX was an independent risk factor for disease-specific survival of stage IV (T4N1-3M0 and T1-3N3M0) gastric cancer patients after curative gastrectomy by multivariate analysis (odds ratio=2.153; 95% confidence interval=1.349-3.435; p=0.001). CONCLUSIONS: Adjuvant CTX may be associated with survival benefit for younger patients with stage IV (T4N1-3M0 and T1-3N3M0) gastric cancer with undifferentiated histology after curative gastrectomy. A randomized controlled trial to reveal the effect of stage-specific adjuvant chemotherapy should be conducted.

Different Clinical Outcomes of Stage IV Gastric Cancer according to the Curability of Surgery

PURPOSE: This study was conducted to evaluate the survival differences between curative stage IV and non-curative stage IV gastric cancers after gastrectomy. METHODS: Stage IV gastric cancer patients who received gastrectomy were selected from our surgical data-base from 1995 to 2004. These patients were separated into two groups according to the curability by surgery. We analyzed the survival differences between curative stage IV patients and non-curative stage IV patients. Survival analysis was performed by Kaplan-Meier survival analysis. RESULTS: During a 10-year period, gastrectomy was performed in 2,214 patients. 224 patients were diagnosed as stage IV. 144 patients were male and 80 patients were female. 97 patients received total gastrectomy. 127 patients received subtotal gastrectomy. 173 patients were diagnosed with curative stage IV and 51 patients were non-curative stage IV. Overall 3-year and 5-year survival rates of stage IV gastric cancer patients in this study were 31.5% and 18.4%. 3-YSR of curative and non-curative stage IV were 36.0% and 16.7% respectively (P-value=0.0204). 5-YSR of curative and non-curative stage IV was 21.9% and 4.2% (P-value=0.0169). CONCLUSION: Significant survival differences were found between curative and non-curative stage IV. Although direct tumor extension or distant metastasis exists, gastrectomy with combined resection was important to improve prognosis if it is possible to resect. When it comes to the matter of survival rate, the subclassification of stage IV gastric cancer should be considered for further management.

Clinical Features of Patients with Stage IV Gastric Cancer

PURPOSE: The early detection of gastric cancer and accuracy of preoperative staging has currently been on the increase due to the development of endoscopy and imaging techniques, but there are still many cases of advanced gastric cancer detected at the first diagnosis and there are also many cases of stage IV gastric cancer diagnosed after a postoperative pathological examination. Although the prognosis of stage IV gastric cancer is very poor, this study was performed to determine the value of the use of aggressive treatment determined after a clinical analysis. MATERIALS AND METHODS: We retrospectively analyzed 150 patients that were diagnosed with stage IV gastric cancer among 1376 patients who underwent a laparotomy for gastric cancer from January 1994 to December 2006. RESULTS: Of the 150 patients with stage IV gastric cancer who underwent a laparotomy, there were 104 men and 46 women. The mean patient age was 57.8 years (age range, 28~93 years). A subtotal gastrectomy or total gastrectomy was performed in 119 patients and 31 patients underwent an explorative laparotomy. The mean survival time of patients that underwent a gastrectomy and patients that did not undergo a gastrectomy was 722 days (range, 14~4,559 days) and 173 days (range, 16~374 days), respectively this result was statistically significant. When patients that underwent a gastrectomy were classified according to the TNM stage, the mean survival time of 33 patients with stage T4 disease was 534 days (range, 17~3,378 days) and the mean survival time of 63 patients with stage N3 disease was 521 days (range, 14~4,190 days), but there was no statistical significance. Chemotherapy was administered to 98 patients and 52 patients did not receive chemotherapy. The mean survival time of patients that received chemotherapy was 792 days (range, 36~4,559 days) and the mean survival time of patients that did not receive chemotherapy was 243 days (range, 14~2,413 days), with statistical significance. CONCLUSION: If there is no evidence of distant metastasis in stage IV gastric cancer, one can expect improvement of the survival rate by the use of aggressive treatment, including curative gastric resection with radical lymph node dissection and chemotherapy.

Clinicopathologic Characteristics of Stage IV Early Gastric Cancer

PURPOSE: Stage IV early gastric carcinoma (EGC) is a rare disease. We report here on 10 cases of EGC that showed metastasis in more than 15 lymph nodes. MATERIALS AND METHODS: A total of 8354 cases of gastric carcinoma in patients who underwent surgical procedures between January 2001 and January 2007 at Samsung Medical Center were studied, and 10 cases were classified as stage IV EGC. We investigated their clinicopathologic characteristics. RESULTS: There were 5 males and 5 females. Their ages at operation ranged from 46 to 76 years with a mean age of 61. All of the 10 patients had undergone curative resection for gastric cancer. The pathological diagnosis confirmed that all of the patients had tumor confined to the submucosa. The median size of the tumors was 5.3cm and the mean number of dissected nodes was 45.5 with a mean number of 22.2 involved nodes. Six cases were classified as the diffuse type and 4 were classified as the intestinal type by Lauren's classification. Histologically, 3 cases were signet ring cell carcinoma, 3 were poorly differentiated, 2 were moderately differentiated and 2 were well differentiated adenocarcinoma. Endolymphatic invasion was found in 9 cases. The median follow-up was 31 months. Adjuvant chemotherapy was done in 9 patients, and the patient who did not receive chemotherapy died by cerebrovascular accident. 2 patient had recurrence of gastric cancer and 7 survived without recurrence. CONCLUSION: More cases should be collected and further studies on the molecular and cellular tumor characteristics are required to characterize these tumors that show aggressive lymphatic spread.

Prognostic Factors of Resected Stage IV Gastric Cancer Patients

PURPOSE: The prognosis of stage IV gastric cancer is poor with the 5-year survival rate still being about 10%. We investigated the prognostic factors of stage IV gastric cancer patients who underwent resection. MATERIALS AND METHODS: A retrospective study of 383 patients with stage IV gastric cancer who underwent surgery in our department between September 1983 to December 2000 was conducted. We classified the 383 patients into two groups: patients surviving 2 years or more (n=77) and those surviving less than 2 years (n=306). Clinicopathologic differences were analyzed between the two groups. We also performed univariate and multivariate analyses of various clinicopathologic factors concerning survival. RESULTS: Statistically significant clinicopathologic differences between the two groups were observed in regard to macroscopic type, distant metastasis, lymph node dissection, curability, and histology. Curability and histology were significant survival factors in 2-year survival. The 5-year survival rate was 5.4% in stage IV gastric cancer. Significant differences in survival among macroscopic type, distant metastasis, lymph node dissection, curability and histology were observed in the univariate analysis. In the Multivariate analysis, Curability, lymph node dissection, and histology were significantly beneficial factors for survival. CONCLUSION: Lymph node dissection, curability, and histology were independent prognostic factors in stage IV gastric cancer, and radical treatment is recommended to improve survival.

pT1N3 Gastric Cancer

PURPOSE: Various minimally invasive surgical techniques, such as an endoscopic mucosal resection and a laparoscopic gastrectomy, are becoming common practice for some cases of early gastric cancer (EGC) defined in terms of the depth of invasion being limited to the mucosa or submucosa. However, there are rare cases of early gastric cancer with massive lymph-node metastasis. MATERIALS AND METHODS: From 6 university hospitals of Korea, 2,772 EGC cases were resected during the various period of analysis (1,432 cases of mucosal cancer and 1,340 of submucosal cancer). RESULTS: As control data, we used the data from a single institute, CHA University Hospital. There were nine cases of early gastric cancer (9/2,772, 0.32%) with N3 lymph node metastasis defined by more than 15 lymph nodes being metastasized according to the UICC-TNM classification (pT1N3, stage IV). Two cases were mucosal cancer (2/1,432, 0.14%), and seven cases were submucosal cancer (7/1,340, 0.52%). Metastasized lymph nodes varied in number from 18 to 52. There were three male and six female patients with a mean age of 57. This is a totally reversed sex ratio compared to the usual gastric cancer or EGC. Among the total of 9 EGC patients, there were 5 who had superficial spreading carcinomas with surface areas larger than 25 cm2. This is a significantly higher proportion compared to the general EGC population. When we compared the tumor size according to the LN status, the N3 group was definitely larger than the other groups. 78% of the pT1N3 cases showed lymphatic invasion, which is very high compared to the 4.7% in general EGC cases. Among the 9 cases, 6 patients had too short a follow-up period to evaluate the correct prognosis, but there was one patient with a non-curative resection and two patients with early recurrence. Although the sample size is small and the follow-up period is short, we can expect a very poor prognosis when we consider the common prognosis of EGC that is widely known and accepted. CONCLUSION: From these results, we can a conclude that the risk factors for pT1N3 gastric cancer are female patients, submucosal invasion, larger tumor size, and lymphatic invasion. However rare, the existence of pT1N3 gastric cancer needs to be taken into consideration, especially during the diagnosis. Furthermore, minimally invasive treatment for EGC needs to be chosen with great precaution. Since the prognosis of pT1N3 gastric cancer is expected to be poor, aggressive adjuvant chemotherapy may be necessary.

Subclassification of Stage IV Gastric Cancer According to the Presence of Distant Metastasis (IVa and IVb)

PURPOSE: The TNM staging system showed limitation in stratifying patients into different prognostic groups with gastric cancer. Since the treatment for stage IV gastric cancer with distant metastasis (M1) is defined as non-curative one, we hypothesized that the survival rate of stage IV gastric cancer with M1 is different to that of stage IV gastric cancer with no distant metastasis (M0), which will provide a rationale to subdivide stage IV into IVa and IVb. MATERIALS AND METHODS: From June 1992 to December 2005, of 1,630 gastric cancer patients who underwent surgery, 308 patients with stage IV gastric cancer were selected and analyzed. The clinicopathologic characteristics and survival of the patients, according to distant metastasis, were determined retrospectively. Median follow-up period was 13 months (range: 1~154 month). RESULTS: 5 year survival rate of M0 and M1 group was 35% and 16% respectively with statistic significance (P=0.0000). When the survival rate of M0 group was analyzed according to the difference of T and M factor, T1-3N3M0 and T4N1-2M0 group showed no significant statistical difference (P=0.1898). CONCLUSION: Given the result in this study, we suggest that the stage IV gastric cancer be subclassified into stage IVa and IVb according to M factor.