Integrated impact of multiple body composition parameters on overall survival in gastrointestinal or genitourinary cancers: A descriptive cohort study.

BACKGROUND: This study aimed to evaluate if combining low muscle mass with additional body composition abnormalities, such as myosteatosis or adiposity, could improve survival prediction accuracy in a large cohort of gastrointestinal and genitourinary malignancies. METHODS: In total, 2015 patients with surgically-treated gastrointestinal or genitourinary cancer were retrospectively analyzed. Skeletal muscle index, skeletal muscle radiodensity, and visceral/subcutaneous adipose tissue index were determined. The primary outcome was overall survival determined by hospital records. Multivariate Cox hazard models were used to identify independent predictors for poor survival. C-statistics were assessed to quantify the prognostic capability of the models with or without incorporating body composition parameters. RESULTS: Survival curves were significantly demarcated by all 4 measures. Skeletal muscle radiodensity was associated with non-cancer-related deaths but not with cancer-specific survival. The survival outcome of patients with low skeletal muscle index was poor (5-year OS; 65.2%), especially when present in combination with low skeletal muscle radiodensity (5-year overall survival; 50.2%). All examined body composition parameters were independent predictors of lower overall survival. The model for predicting overall survival without incorporating body composition parameters had a c-index of 0.68 but increased to 0.71 with the inclusion of low skeletal muscle index and 0.72 when incorporating both low skeletal muscle index and low skeletal muscle radiodensity/visceral adipose tissue index/subcutaneous adipose tissue index. CONCLUSION: Patients exhibiting both low skeletal muscle index and other body composition abnormalities, particularly low skeletal muscle radiodensity, had poorer overall survival. Models incorporating multiple body composition prove valuable for mortality prediction in oncology settings.

Impacts of tumor microenvironment during neoadjuvant chemotherapy in patients with esophageal squamous cell carcinoma.

With the advent of immune checkpoint inhibitors (ICIs), a better understanding of tumor microenvironment (TME) is becoming crucial in managing esophageal squamous cell carcinoma (ESCC) patients. We investigated the survival impact of TME status and changes in patients with ESCC who underwent neoadjuvant chemotherapy (NAC) followed by surgery (n = 264). We examined immunohistochemical status (CD4+, CD8+, CD20+, Foxp3+, HLA class-1+, CD204+, and programmed death ligand-1 [PD-L1+]) on 264 pre-NAC and 204 paired post-NAC specimens. Patients were classified by their pre- and post-NAC immune cell status and their changes following NAC. Our findings showed that pre-NAC TME status was not significantly associated with survival outcomes. In contrast, post-NAC TME status, such as low level of T cells, CD4+ T cells, and high PD-L1 combined positive score (CPS), were significantly associated with poor overall survival (OS). Notably, TME changes through NAC exerted significant survival impacts; patients with consistently low levels of T cells, low levels of CD4+ T cells, or high levels of PD-L1 (CPS) had very poor OS (3-year OS: 35.5%, 40.2%, and 33.3%, respectively). Tumor microenvironment changes of consistently low T cells, low CD4+ T cells, and high PD-L1 were independent predictors of poor OS in multivariate Cox hazards analyses, while factors indicating post-NAC status (T cells, CD4+, and PD-L1 [CPS]) alone were not. Therefore, we suggest that the consistently low T/high PD-L1 group could benefit from additional therapies, such as ICIs, and the importance of stratification by the TME, which has recently been recognized.

The importance of ethnic-specific cut-offs of low muscle mass for survival prediction in oncology.

BACKGROUND & AIMS: While skeletal muscle index (SMI) is the most widely used indicator of low muscle mass (or sarcopenia) in oncology, optimal cut-offs (or definitions) to better predict survival are not standardized. METHODS: We compared five major definitions of SMI-based low muscle mass using an Asian patient cohort with gastrointestinal or genitourinary cancers. We analyzed 2015 patients with surgically-treated gastrointestinal (n = 1382) or genitourinary (n = 633) cancer with pre-surgical computed tomography images. We assessed the associations of clinical parameters, including low muscle mass by each definition, with cancer-specific survival (CSS) and overall survival (OS). RESULTS: During a median follow-up period of 61 months, 303 (15%) died of cancer, and 147 died of other causes. An Asian-based definition diagnosed 17.8% of patients as having low muscle mass, while the other Caucasian-based ones classified most (>70%) patients as such. All definitions significantly discriminated both CSS and OS between patients with low or normal muscle mass. Low muscle mass using any definition but one predicted a lower CSS on multivariate Cox regression analyses. All definitions were independent predictors of lower OS. The original multivariate model without incorporating low muscle mass had c-indices of 0.63 for CSS and 0.66 for OS, which increased to 0.64-0.67 for CSS and 0.67-0.70 for OS when low muscle mass was considered. The model with an Asian-based definition had the highest c-indices (0.67 for CSS and 0.70 for OS). CONCLUSIONS: The Asian-specific definition had the best predictive ability for mortality in this Asian patient cohort.

Survival outcomes of esophageal cancer patients with recurrence after curative treatments.

BACKGROUND: Little is known about predictive factors for survival outcomes of esophageal carcinoma (EC) patients who developed recurrence after undergoing multimodal therapies. We aimed to investigate long-term outcomes and identify prognostic factors in patients with relapsed EC, focusing especially on those with oligometastasis (OM). METHODS: EC patients who developed recurrence after curative treatments (radical esophagectomy or definitive chemoradiotherapy (dCRT)) between 2010 and 2017 were reviewed. Multivariate Cox hazards models were applied to determine independent predictors of poor post-recurrence survival (PRS). RESULTS: In total, 178 patients were included. The median PRS was 12.9 months. Of the 178 patients, 98 had OM and 80 non-OM (NOM) disease. The survival outcomes of patients with OM were significantly better than those of patients with NOM (P < 0.01). Surgical treatments provided significantly better survival outcomes than CRT or chemo-/radiotherapy alone (3-year overall survival (OS); 78.1% vs. 42.5% vs. 28.9%, P < 0.01), mainly due to prolonging survival after the recurrence (3-year PRS 62.9% vs. 16.7% vs. 16.2%, P < 0.01). Multivariable analysis focusing on patients with OM revealed cStage III-IV disease (P < 0.01), high GPS at the time of recurrence (P = 0.02) and non-curative treatments (P < 0.01), to be independently associated with poor PRS. In contrast, in patients with NOM, no independent predictors for poor PRS were identified. CONCLUSIONS: The survival outcomes of patients with relapsed EC remain poor. Surgical treatments could provide survival benefits for patients with recurrent EC, especially for patients with OM.

Survival Impacts of Impaired Lung Functions and Comorbidities on Elderly Esophageal Cancer Patients.

BACKGROUND: Preoperative physiological assessments are crucial for optimizing clinical outcomes, especially those of elderly esophageal cancer (EC) patients who are generally frail and at the high risk of mortality. METHODS: Patients who underwent surgery for EC between 2004 and 2018 were retrospectively reviewed. Patients were categorized into elderly (>70 years) or non-elderly (≤70 years) groups. Various physiological parameters including the Charlson Comorbidity Index (CCI), immunonutritional parameters and pulmonary functions were studied. Pulmonary functions included %vital capacity (VC) and forced expiratory volume in one second (FEV1.0) and FEV1.0%. The thresholds were set as the lowest quartile (100% for %VC and 2L for FEV1.0) in this cohort. Multivariate Cox hazards models were applied to determine independent predictors of non-EC-related deaths. RESULTS: In total, 824 patients were included (elderly; n = 306, non-elderly; n = 518). Elderly patients had a significantly lower 5-year OS rate than non-elderly patients (53.3% vs. 57.2%, P = 0.03), mainly due to increased risk of death from non-EC related causes. In the elderly group, multivariate Cox hazards analysis identified 3 independent predictors of non-EC-related deaths; high CCI (HR 1.98, P=0.006), low %VC (HR 2.01, P = 0.004) and low FEV1.0 (HR 1.6, P=0.048). Elderly patients without risk factors had a significantly better 5-year OS rate (63.5%) than those with 1 (50.0%) or 2-3 (36.3%) risk factors (P <0.01). Deaths due to pulmonary disease rose significantly as the number of risk factors increased (P=0.03). CONCLUSIONS: The severity of comorbidities and pulmonary function impairments are useful for predicting long-term outcomes, especially non-EC-related deaths, in elderly EC patients.

Combined tubular adenocarcinoma, neuroendocrine carcinoma and adenocarcinoma with enteroblastic differentiation arising in Barrett esophagus.

Adenocarcinoma (AC) with neuroendocrine carcinoma (NEC) or enteroblastic (ENT) differentiation rarely develops in Barrett's esophagus (BE). A 76-year-old man was diagnosed with Barrett's AC (cT1bN0M0) and underwent thoracoscopic esophagectomy. A type 0-IIc + 0-Is lesion measuring 26 × 21 mm was macroscopically observed on a background of long segment BE (pT1bN0M0). The tumor comprised three different histological types of carcinoma (NEC, AC with ENT differentiation and moderately differentiated AC). NEC showed positivity for synaptophysin, chromogranin A and insulinoma-associated protein 1 with a Ki-67 index of 60.6%. ENT tumors were immunopositive for AFP and sal-like protein 4, and focally immunopositive for human chorionic gonadotrophin. The amounts of NEC, ENT and AC were 40%, 40% and 20%, respectively. p53 expression was positive throughout the tumor. Rb expression was negative at the NEC, but positive at the ENT and AC. CD4 and CD8 densities were lower in the NEC segment than in the AC and ENT segments, and PD-L1 expression was negative throughout the tumor. Early cancer arising in BE with a combination of tubular AC, ENT tumors and NEC is very rare. Our observations might contribute to understanding the carcinogenetic pathways and tumor microenvironment of NEC and ENT tumors.

McKeown esophagectomy for a thoracic esophageal carcinoma patient who has a history of definitive chemoradiotherapy for esophageal carcinoma and total pharyngolaryngectomy for hypopharyngeal cancer.

A 64-year-old man, who had previously undergone definitive chemoradiotherapy (dCRT) and endoscopic resections for metachronous multiple esophageal squamous cell carcinoma (ESCC) and had also received total pharyngolaryngectomy (TPL) for hypopharyngeal cancer, was diagnosed with ESCC in the middle thoracic esophagus (cT3N0M0). Thoracoscopic McKeown esophagectomy was performed for the patient. Although the tumor was tightly adherent to the thoracic duct and both main bronchi, they were successfully mobilized. In order to maintain the blood supply to the trachea, we preserved the bilateral bronchial arteries and avoided prophylactic upper mediastinal lymph node dissection. Cervical end-to-side anastomosis between the jejunum and a gastric conduit was performed. Minor pneumothorax was managed conservatively, and the patient was discharged 44 days after the surgery. Overall, thoracoscopic McKeown esophagectomy was safely performed in a patient with a history of TPL and dCRT. Surgeons should be very careful to prevent tracheobronchial ischemia by optimizing the extent of lymph node dissection.

The Impact of Pretreatment Esophageal Stenosis on Survival of Esophageal Cancer Patients.

BACKGROUND: Little is known about the survival impacts of pretreatment cancerous stenosis on patients with esophageal carcinoma (EC). METHODS: The clinicopathologic characteristics of patients who underwent surgery for EC between January 2010 and December 2018 were retrospectively reviewed. Esophageal stenosis was defined as present when a thin endoscope could not be passed through the tumor site. The impacts of stenosis on overall survival (OS) and cancer-specific survival (CSS) were evaluated using Cox hazards analysis. RESULTS: Of the 496 EC patients in this study, 51 (10.3 %) had pretreatment esophageal stenosis. Stenosis was associated with lower body mass index (P < 0.001) and higher pStage (P < 0.001). The 3-year OS rate for the patients with stenosis was significantly poorer than for the patients without stenosis (40.2 % vs 69.6 %; hazard ratio [HR], 2.19; P < 0.001). The survival outcomes, especially CSS, for the patients with stenosis were significantly poorer than for the patients without stenosis for both pStage II-III (P = 0.009) and pStage IV (P = 0.006) disease. The OS and CSS curves were well stratified by the presence of stenosis even in early-stage (pStage II) patients (P = 0.04 and P < 0.01, respectively). Multivariable analysis showed esophageal stenosis, pStage III-IV disease, and non-curative resection to be independently associated with poor OS (HR, 1.61; P = 0.02) and poor CSS (HR,1.67; P = 0.02). Higher pStage was an independent predictor of poor CSS for patients without stenosis, but not for those with stenosis. CONCLUSIONS: Esophageal carcinoma patients with pretreatment stenosis had significantly poorer survival outcomes, especially poorer CSS, than those without stenosis in both early- and advanced-stage diseases.

Influences of intratumoral heterogeneity on assessment of tumor microenvironment in esophageal squamous cell carcinoma.

The intratumoral heterogeneity (ITH) of the tumor microenvironment (TME) has yet to be addressed in esophageal squamous cell carcinoma (ESCC). Here, we studied the ITH of CD8 and PD-L1 status in ESCC, and examined the potential of the tumor surface for representing the TME. In total, 67 surgically resected clinical Stage II ESCC specimens were analyzed. The CD8-cell density, PD-L1 tumor proportion score (TPS), and combined positive score (CPS) were calculated in three (superficial, middle, and deep) areas of each specimen. ITH was quantified by distance-standardized coefficient variations of the three values. The CD8 and PD-L1 status of each area was dichotomized and tumor-surface capabilities for predicting the entire tumor status were estimated. Variables were compared according to the presence of neoadjuvant chemotherapy (NAC). The ITH, especially PD-L1 heterogeneity, differed markedly among specimens. The concordance rates of CD8 and PD-L1 (CPS and TPS) status among the three different areas were 71.6%, 74.6%, and 73.1%, respectively. The sensitivity and the specificity of the tumor surface for predicting the CD8 status of the whole tumor were high, especially in the NAC- group (both 1.0). The tumor surface also showed high capabilities for representing the whole PD-L1 status, while yielding moderate positive predictive values (0.70). The ITH degrees and predictive capabilities did not differ according to NAC. Taken together, the ITH of CD8 and PD-L1 differed among ESCC specimens, while not being markedly affected by NAC. The use of a biopsy specimen from the tumor surface might be feasible for TME evaluation.

Combining nutritional status with TNM stage: a physiological update on gastric cancer staging for improving prognostic accuracy in elderly patients.

BACKGROUND: The tumor-node-metastasis (TNM) staging system does not take the patient's physiological status into consideration, reportedly making it insufficient for predicting survival outcomes in frail cancer patients. We assessed the prognostic values of several nutrition- and inflammation-based markers in combination with pTNM stage in gastric carcinoma (GC) patients. METHODS: In total, 1166 patients undergoing GC surgery were studied. The prognostic capabilities of 3 nutritional and 3 systemic inflammatory parameters were examined. We developed new staging systems by adding these markers, individually, to the pTNM stage. We then compared the prognostic capabilities of our new systems with that of pTNM stage alone. We also assessed the prognostic values of these systems by dividing our patient cohort into elderly (≥ 65 years) and non-elderly groups. RESULTS: Our novel staging systems had greater predictive capabilities for overall survival (OS) than pTNM alone. Most notably, survival discrimination was significantly increased for pTNM when it was combined with albumin-based nutritional indices (geriatric nutritional risk index (GNRI) and prognostic nutritional index (PNI)). Our new staging systems incorporating GNRI or PNI into pTNM had significantly better predictive capability for OS, especially non-GC mortality, than pTNM alone in elderly GC patients. In the non-elderly patients, the predictive capabilities of the new staging systems for OS differed minimally from that of pTNM. CONCLUSIONS: The predictive capability of pTNM stage was particularly enhanced when this parameter was combined with nutritional markers. Our new approach aids in predicting survival outcomes, especially non-GC-related death, in elderly GC patients.

Impacts of complications after esophageal cancer surgery on health-related quality of life and nutritional status.

BACKGROUND: The long-term impacts of post-operative complications, especially pulmonary complications and anastomotic leakage, on health-related quality of life (HRQoL), nutritional status and body composition remain to be fully addressed in patients undergoing esophageal cancer surgery. METHODS: Patients who underwent esophagectomy between 2015 and 2019 and survived without recurrence were eligible. HRQoL (European Organization for Research and Treatment of Cancer QLQ-C30 and the QLQ-OES18 questionnaires), nutritional and body composition data were prospectively evaluated before and at 3, 6, 12 and 24 months after surgery. Collected data were compared between patients with post-operative complications and those without. RESULTS: In total, 88 patients were included. Overall complications, anastomotic leakage and pulmonary complications developed in 48 (54.5%), 20 (20.7%) and 18 (20.5%) patients, respectively. Patients with pulmonary complications had significantly more reflux-related symptoms (dry mouth; P = 0.03, coughing; P = 0.047), and more difficulties with eating at 24 months after surgery, as compared to those without such complications. Anastomotic leakage increased pain, speaking problems and dysphagia up to 6 months after surgery. Patients with pulmonary complications had significantly lower prealbumin levels (P = 0.01, 0.02 and 0.008 at 6, 12 and 24 months after surgery, respectively) and lower prognostic nutritional index values over time after surgery than those without these complications. In contrast, anastomotic leakage was not associated with poor nutritional status post-operatively. Body composition was not affected by the occurrence of complications. CONCLUSION: Patients who developed post-operative complications, especially pulmonary complications, had long-lasting negative HRQoL outcomes and poor nutritional status after esophagectomy.

Survival Prediction Capabilities of Preoperative Inflammatory and Nutritional Status in Esophageal Squamous Cell Carcinoma Patients.

BACKGROUND: Studies have revealed the impacts of various inflammatory and nutritional markers in patients with esophageal squamous cell carcinoma (ESCC). We evaluated the prognostic values of multiple inflammation- or nutrition-based markers, either alone or in combination with pStage, in ESCC patients. METHODS: In total, 360 patients undergoing upfront surgery for ESCC were retrospectively reviewed. The prognostic capabilities of 7 inflammatory and 3 nutritional parameters were investigated. Furthermore, we devised new staging systems by adding these markers to pStage and examined the prognostic abilities of our new approach. Time-dependent receiver operating characteristic curves and the areas under the curve (AUCs) were estimated to compare prognostic capabilities among the parameters. RESULTS: The AUCs for predicting overall survival (OS) of the prognostic nutritional index (PNI), CRP to albumin ration (CAR), lymphocyte to CRP ratio (LCR) and the Naples prognostic score (NPS) were similar to that of pStage. Notably, CAR and LCR showed high predictive capabilities for OS (AUCs; 0.627 and 0.634 for 3-year OS, respectively). New staging systems combining inflammatory or nutritional markers with pStage provided higher AUCs for predicting OS than pStage alone. In particular, NPpStage (NPS and pStage) (P = 0.03), PNpStage (PNI and pStage) (P = 0.03) and LCpStage (LCR and pStage) (P = 0.05) showed significantly higher accuracy for predicting OS than pStage alone. CONCLUSIONS: Various inflammatory or nutritional markers, especially those derived from CRP, are useful for predicting survival outcomes of ESCC patients. The predictive capabilities of these indices were augmented when used in combination with pStage.

Efficacy and safety of a third-generation oncolytic herpes virus G47Δ in models of human esophageal carcinoma.

Treatment options are limited for esophageal carcinoma (EC). G47Δ, a triple-mutated, conditionally replicating herpes simplex virus type 1 (HSV-1), exhibits enhanced killing of tumor cells with high safety features. Here, we studied the efficacy of G47Δ using preclinical models of human EC. In vitro, G47Δ showed efficient cytopathic effects and replication capabilities in all eight human esophageal cancer cell lines tested. In athymic mice harboring subcutaneous tumors of human EC (KYSE180, TE8, and OE19), two intratumoral injections with G47Δ significantly inhibited the tumor growth. To mimic the clinical treatment situations, we established an orthotopic EC model using luciferase-expressing TE8 cells (TE8-luc). An intratumoral injection with G47Δ markedly inhibited the growth of orthotopic TE8-luc tumors in athymic mice. Furthermore, we evaluated the safety of applying G47Δ to the esophagus in mice. A/J mice inoculated intraesophageally or administered orally with G47Δ (107 plaque-forming units [pfu]) survived for more than 2 months without remarkable symptoms, whereas the majority with wild-type HSV-1 (106 pfu) deteriorated within 10 days. PCR analyses showed that the G47Δ DNA was confined to the esophagus after intraesophageal inoculation and was not detected in major organs after oral administration. Our results provide a rationale for the clinical use of G47Δ for treating EC.

Oncolytic herpes virus G47Δ works synergistically with CTLA-4 inhibition via dynamic intratumoral immune modulation.

Oncolytic virus therapy can increase the immunogenicity of tumors and remodel the immunosuppressive tumor microenvironment, leading to an increased antitumor response to immune-checkpoint inhibitors. Here, we investigated the therapeutic potential of G47Δ, a third-generation oncolytic herpes simplex virus type 1, in combination with immune-checkpoint inhibitors using various syngeneic murine subcutaneous tumor models. Intratumoral inoculations with G47Δ and systemic anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody administration caused an enhanced antitumor activity when combined and worked synergistically. Conversely, the efficacy of G47Δ in combination with anti-programmed cell death protein-1 (PD-1) antibody was equivalent to that of the anti-PD-1 antibody alone in all murine models examined. The combination of intratumoral G47Δ and systemic anti-CTLA-4 antibody was shown to recruit effector T cells into the tumor efficiently while decreasing regulatory T cells. Furthermore, a wide range of gene signatures related to inflammation, lymphoid lineage, and T cell activation was highly upregulated with the combination therapy, suggesting the conversion of immune-insusceptible tumors to immune susceptible. The therapeutic effect proved tumor specific and long lasting. Immune cell subset depletion studies demonstrated that CD4+ T cells were required for synergistic curative activity. The results depict the dynamics of immune modulation of the tumor microenvironment and provide a clinical rationale for using G47Δ with immune checkpoint inhibitors.

Multidisciplinary treatment strategy for locally advanced gastric cancer: A systematic review.

BACKGROUND: Multidisciplinary management of patients with locally advanced gastric cancer (LAGC) remains unstandardized worldwide. We performed a systemic review to summarize the advancements, regional differences, and current recommended multidisciplinary treatment strategies for LAGC. METHODS: Eligible studies were identified through a comprehensive search of PubMed, Web of Science, Cochrane Library databases and Embase. Phase 3 randomized controlled trials which investigated survival of patients with LAGC who underwent gastrectomy with pre-/perioperative, postoperative chemotherapy, or chemoradiotherapy were included. RESULTS: In total, we identified 11 studies of pre-/perioperative chemotherapy, 38 of postoperative chemotherapy, and 14 of chemoradiotherapy. In Europe and the USA, the current standard of care is perioperative chemotherapy for patients with LAGC using the regimen of 5-FU, folinic acid, oxaliplatin and docetaxel (FLOT). In Eastern Asia, upfront gastrectomy and postoperative chemotherapy is commonly used. The S-1 monotherapy or a regimen of capecitabine and oxaliplatin (CapOx) are used for patients with stage II disease, and the CapOx regimen or the S-1 plus docetaxel regimen are recommended for those with stage III Gastric cancer (GC). The addition of postoperative radiotherapy to peri- or postoperative chemotherapy is currently not recommended. Additionally, clinical trials testing targeted therapy and immunotherapy are increasingly performed worldwide. CONCLUSIONS: Recent clinical trials showed a survival benefit of peri-over postoperative chemotherapy and chemoradiotherapy. As such, this strategy may have a potential as a global standard for patients with LAGC. Outcome of the ongoing clinical trials is expected to establish the global standard of multidisciplinary treatment strategy in patients with LAGC.

The different survival impacts of body mass index in elderly and non-elderly patients with gastric carcinoma.

BACKGROUND: The age-dependent survival impact of body mass index (BMI) remains to be fully addressed in patients with gastric carcinoma (GC). We investigated the prognostic impacts of BMI in elderly (≥70 years) and non-elderly patients undergoing surgery for GC. METHODS: In total, 1168 GC patients were retrospectively reviewed. Patients were stratified into 3 groups according to BMI; low (<20), medium (20-25) and high (>25). The effects of BMI on overall survival (OS) and cancer-specific survival (CSS) were assessed using univariate and multivariate Cox hazards models. RESULTS: There were 242 (20.7%), 685 (58.7%) and 241 (20.6%) patients in the low-, medium- and high-BMI groups, respectively. The number of patients with high BMI but decreased muscle mass was extremely small (n = 13, 1.1%). Patients in the low-BMI group exhibited significantly poorer OS than those in the high- and medium-BMI group (P < 0.001). Notably, BMI classification significantly demarcated OS and CSS curves (both P < 0.001) in non-elderly patients, while did not in elderly patients (OS; P = 0.07, CSS; P = 0.54). Furthermore, the survival discriminability by BMI was greater in pStage II/III disease (P = 0.006) than in pStage I disease (P = 0.047). Multivariable analysis focusing on patients with pStage II/III disease showed low BMI to be independently associated with poor OS and CSS only in the non-elderly population. CONCLUSIONS: BMI-based evaluation was useful for predicting survival and oncological outcomes in non-elderly but not in elderly GC patients, especially in those with advanced GC.

Esophageal cancer patients' survival after complete response to definitive chemoradiotherapy: a retrospective analysis.

BACKGROUND: Chemoradiotherapy is an alternative to surgery for esophageal cancer, with a putatively equivalent outcome. However, disease recurrence after a complete response is common and if follow-up surveillance detects recurrence, salvage treatments for potentially curable disease must follow. METHODS: We conducted a nation-wide questionnaire survey of institutions in Japan certified by the Japanese Esophageal Society to investigate outcomes of primary thoracic esophageal cancer patients initially treated by chemoradiotherapy with complete response diagnoses. The primary endpoint was overall survival, the secondary endpoint disease recurrence. Outcomes of patients who had undergone salvage treatments were also investigated. Cases were excluded from analysis if endoscopic study, endoscopic biopsy, or computed tomography data were lacking. RESULTS: At 41 institutes 544 case records were collected; valid data on 392 patients were obtained; 5-year survival was 74.8%, 5-year disease-free survival, 66.8%. Clinical staging before treatment significantly affected both overall and disease-free survival rates, but differences between adjoining stages were unexpectedly small. The primary relapse site was classified as primary site (n = 58), regional lymph nodes (n = 36), or distant disease (n = 34). Salvage treatments with curative intent (surgery, endoscopic treatments, and additional radiation) were performed on 38, 23, and 4 cases; 5-year survival after esophagectomy (n = 22), endoscopic treatment (n = 23), and lymphadenectomy (n = 9) was 47.4%, 70.9%, and 33.3%, respectively. CONCLUSIONS: A quarter of patients developed recurrent disease, mostly locoregional, after complete response. Complete response patients with originally advanced stage disease had fair clinical outcomes; salvage treatments after locoregional recurrence achieved modest long-term survival.

Prognosis of hemodialysis patients undergoing surgery for gastric cancer: Results of a multicenter retrospective study.

BACKGROUND: Little is known about the survival outcomes of and predictive factors for survival in hemodialysis patients undergoing surgery for gastric cancer. METHODS: We performed a multicenter retrospective study from 9 institutions to investigate the survival outcomes of 75 hemodialysis patients with gastric cancer. Patient characteristics included demographic data, hemodialysis- and gastric cancer-related variables. Multivariate Cox hazards models were applied to determine independent predictors of poor overall survival and non-gastric cancer related death. RESULTS: Stage I disease was predominant (58.7%) in our series. The overall morbidity and the 30-day mortality rates were 25.3% and 1.3%, respectively. The 5-year overall survival rates of patients with pStages I, II, III, and IV disease were 59.2%, 42.9%, 32.3%, and 0%, respectively. Eleven (14.7%) patients died of gastric cancer, whereas many more (40.0%) died owing to causes other than gastric cancer. Non-gastric cancer-related death was especially prevalent in patients with pStages I (95.2%) and II (75.0%) disease. Multivariable analysis revealed advanced age, long duration of hemodialysis (> 5 years), total gastrectomy, and pStage IV disease to be independently associated with poor overall survival. Notably, advanced age, long duration of hemodialysis, and the presence of cardiovascular disease were all independent predictors of non-gastric cancer-related death. Patients with all 3 factors had very poor survival outcomes (3-year overall survival; 14.3%). CONCLUSION: The survival outcomes of hemodialysis patients with gastric cancer, especially those with early-stage gastric cancer, were clearly poor, largely owing to the increased risk of non-gastric cancer-related death. Preoperative comorbidities and hemodialytic features were useful for predicting long-term outcomes of this vulnerable population.