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The association of computed tomography (CT)-derived skeletal muscle index (SMI) and skeletal muscle radiodensity (SMD) with postoperative prognosis in patients with gastric cancer (GC) remains unknown. Therefore, the present study aimed to assess the association between SMI and SMD with 5-year overall survival (OS) and recurrence-free survival (RFS) in patients with GC. SMI and SMD were measured preoperatively in patients who underwent gastrectomy. Patients were categorized into Groups 1 (high SMI and SMD), 2 (high SMI or SMD) and 3 (low SMI and SMD). OS and RFS rates were assessed using Kaplan-Meier analysis and the log-rank test. Among 459 patients, OS and RFS rates were significantly lower in the low-SMD group than in the high-SMD group (OS, 83.4% vs. 88.8%, respectively; P=0.04 and RFS, 80.5% vs. 87.2%, respectively; P=0.02). OS and RFS rates were also significantly lower in Group 3 than in Groups 2 and 1 (P=0.006). Multivariate analysis revealed that a low SMI and SMD (Group 3) was a significant independent prognostic factor for OS [hazard ratio (HR), 2.32; 95% confidence interval (CI), 1.17-4.59; P=0.016] and RFS (HR, 2.28; 95% CI, 1.19-4.37; P=0.013). In summary, low SMI and SMD values may be useful postoperative prognostic indicators for patients with GC.
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BACKGROUND/AIM: The Inflammatory Burden Index (IBI) has been reported as a novel prognostic indicator in several cancers and diseases. However, research on the IBI in patients with gastric cancer (GC) after gastrectomy is insufficient. This study investigated the utility of the preoperative IBI as a prognostic indicator in patients with GC. PATIENTS AND METHODS: This retrospective study enrolled 459 patients undergoing gastrectomy for GC between 2013 and 2017 at the Kanagawa Cancer Center, Kanagawa, Japan. The IBI was calculated from preoperative blood test data. We evaluated the relationship between the preoperative IBI and clinicopathologic factors, overall survival (OS), and recurrence-free survival (RFS) after gastrectomy for GC, using propensity score matched analysis. RESULTS: Regarding the association between IBI and clinicopathologic features, the high-IBI group was significantly older and had more lymphatic invasion and more progressive pT status than the low-IBI group before propensity score-matched analysis. OS and RFS after curative surgery were significantly lower in patients with a high IBI than in those with a low IBI (77.5% vs. 86.1%; p=0.02 and 74.3% vs. 85.1%; p=0.03, respectively). Multivariate analysis identified high IBI as an independent predictor of both OS and RFS. CONCLUSION: Preoperative IBI may serve as a valuable prognostic indicator for patients undergoing curative gastrectomy for GC.
Subject(s)
Gastrectomy , Inflammation , Propensity Score , Stomach Neoplasms , Humans , Stomach Neoplasms/surgery , Stomach Neoplasms/pathology , Stomach Neoplasms/mortality , Gastrectomy/adverse effects , Gastrectomy/mortality , Female , Male , Aged , Prognosis , Middle Aged , Retrospective Studies , Inflammation/pathology , Aged, 80 and over , AdultABSTRACT
BACKGROUND/AIM: The sex-specific effect of the visceral-to-subcutaneous fat ratio (VSR) before gastrectomy on postoperative survival in patients with gastric cancer (GC) remains unclear. This study measured the preoperative VSR in patients with GC and analyzed its relationship with 5-year overall survival (OS) and relapse-free survival (RFS) by sex. PATIENTS AND METHODS: This prospective study included 540 patients with GC undergoing gastrectomy. Preoperative visceral and subcutaneous fat volumes were measured using computed tomography, and the VSR was calculated. A cutoff value for the VSR was established using 5-year survival data, and its association with survival was analyzed using the Kaplan-Meier method, log-rank tests, and multivariate regression analysis. RESULTS: Among the 459 patients analyzed (300 males and 159 females), OS and RFS were significantly lower in the low-VSR group than in the high-VSR group in males (OS: 76.2% vs. 88.1%, p=0.01; RFS: 74.6% vs. 86.0%, p=0.02). In females, no difference in OS was observed between the groups, whereas the high-VSR group had significantly lower RFS than that of the low-VSR group (RFS: 74.7% vs. 88.9%, p=0.01). Multivariate analysis showed that a low VSR was an independent poor predictor of OS in males and a high VSR was an independent poor predictor of RFS in females. CONCLUSION: In patients with GC, the sex-dependent preoperative VSR was a potentially useful predictor of postoperative survival.
Subject(s)
Gastrectomy , Intra-Abdominal Fat , Stomach Neoplasms , Subcutaneous Fat , Humans , Stomach Neoplasms/surgery , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Stomach Neoplasms/diagnostic imaging , Male , Female , Subcutaneous Fat/diagnostic imaging , Subcutaneous Fat/pathology , Intra-Abdominal Fat/diagnostic imaging , Intra-Abdominal Fat/pathology , Middle Aged , Aged , Gastrectomy/mortality , Prospective Studies , Sex Factors , Prognosis , Preoperative Period , Adult , Postoperative Period , Aged, 80 and over , Kaplan-Meier Estimate , Tomography, X-Ray ComputedABSTRACT
BACKGROUND/AIM: This study aimed to investigate the differences in the postoperative dietary intake (DI) loss between men and women after radical resection for early gastric cancer (GC), and to identify effective nutritional support for both sexes. PATIENTS AND METHODS: This prospective, observational study enrolled patients who underwent gastrectomy for GC. DI was assessed using the food frequency questionnaire containing 82 food items (FFQW82) during nutritional counseling before surgery and one and three months postoperatively. RESULTS: The median preoperative DI of all participants was 1,856.3 kcal/day, and DI at 1 and 3 months were 1,532.5 kcal/day and 1,637 kcal/day, respectively. The median preoperative DI was 1805 kcal/day (1,300-2,330 kcal/day) and 1481 kcal/day (1,126-1,957 kcal/day) in men and women, respectively (p<0.0001). The median DI at 1 month was 1627 (1,101-2,195) kcal/day and 1,308 (986-1,915) kcal/day in men and women, respectively (p<0.0001). At 3 months postoperatively, the median DI was 1737 (1,130-2,443) kcal/day in men and 1428 (816-2,005) kcal/day in women (p<0.0001). However, there was no significant difference in the DI loss rate at 1 month (median: -9.7% vs. -9.3%, p=0.765) and 3 months (median: -3.5% vs. -4.8%, p=0.137) between men and women. CONCLUSION: Although the DI loss rate in men and women after gastrectomy for GC was almost similar, the postoperative DI and DI loss differed significantly. Therefore, differences in DI loss after gastrectomy between men and women should be considered while assessing the efficacy of additional nutritional support such as oral nutritional supplements after gastrectomy.
Subject(s)
Gastrectomy , Stomach Neoplasms , Humans , Stomach Neoplasms/surgery , Gastrectomy/methods , Gastrectomy/adverse effects , Male , Female , Middle Aged , Aged , Prospective Studies , Energy Intake , Sex Factors , Postoperative Period , Eating , AdultABSTRACT
BACKGROUND: Neoadjuvant therapy is the standard treatment for patients with locally advanced oesophageal squamous cell carcinoma (OSCC). However, the prognosis remains poor and more intensive neoadjuvant treatment might be needed to improve patient outcomes. We therefore aimed to compare the efficacy and safety of neoadjuvant doublet chemotherapy, triplet chemotherapy, and doublet chemotherapy plus radiotherapy in patients with previously untreated locally advanced OSCC. METHODS: In this randomised, open-label, phase 3 trial, patients aged 20-75 years with previously untreated locally advanced OSCC and an Eastern Cooperative Oncology Group performance status of 0 or 1 were recruited from 44 centres across Japan. Patients were randomly assigned (1:1:1) centrally via a web-based system to receive neoadjuvant doublet chemotherapy (two courses of fluorouracil [800 mg/m2 per day intravenously on days 1-5] and cisplatin [80 mg/m2 per day on day 1] separated by an interval of 3 weeks [NeoCF]), triplet chemotherapy (three courses of fluorouracil [750 mg/m2 per day on days 1-5], cisplatin [70 mg/m2 per day on day 1], and docetaxel [70 mg/m2 per day on day 1] repeated every 3 weeks [NeoCF+D]), or doublet chemotherapy (two courses of fluorouracil [1000 mg/m2 per day on days 1-4] and cisplatin [75 mg/m2 per day on day 1] separated by an interval of 4 weeks) plus 41·4 Gy radiotherapy [NeoCF+RT]) followed by oesophagectomy with regional lymph node dissection. Randomisation was stratified by T stage and institution. Participants, investigators, and those assessing outcomes were not masked to group assignment. The primary endpoint was overall survival, analysed by intention to treat. Analysis of safety included all patients who received at least one course of chemotherapy, and analysis of surgical complications included those who also underwent surgery. This study is registered with the Japan Registry of Clinical Trials, jRCTs031180202, and the trial is complete. FINDINGS: A total of 601 patients (529 male individuals and 72 female individuals) were randomly assigned between Dec 5, 2012, and July 20, 2018, with 199 patients in the NeoCF group, 202 patients in the NeoCF+D group, and 200 patients in the NeoCF+RT group. Compared with the NeoCF group, during a median follow-up period of 50·7 months (IQR 23·8-70·7), the 3-year overall survival rate was significantly higher in the NeoCF+D group (72·1% [95% CI 65·4-77·8] vs 62·6% [55·5-68·9]; hazard ratio [HR] 0·68, 95% CI 0·50-0·92; p=0·006) but not in the NeoCF+RT group (68·3% [61·3-74·3]; HR 0·84, 0·63-1·12; p=0·12). Grade 3 or higher febrile neutropenia occurred in two (1%) of 193 patients in the NeoCF group, 32 (16%) of 196 patients in the NeoCF+D group, and nine (5%) of 191 patients in the NeoCF+RT group. Treatment-related adverse events leading to termination of neoadjuvant therapy were more common in the NeoCF+D group (18 [9%] of 202 participants) than in the NeoCF+RT group (12 [6%] of 200) and NeoCF group (eight [4%] of 199). There were three (2%) treatment-related deaths during neoadjuvant therapy in the NeoCF group, four (2%) deaths in the NeoCF+D group, and two (1%) deaths in the NeoCF+RT group. Grade 2 or higher postoperative pneumonia, anastomotic leak, and recurrent laryngeal nerve paralysis were reported in 19 (10%), 19 (10%), and 28 (15%) of 185 patients, respectively, in the NeoCF group; 18 (10%), 16 (9%), and 19 (10%) of 183 patients, respectively, in the NeoCF+D group; and 23 (13%), 23 (13%), and 17 (10%) of 178 patients, respectively, in the NeoCF+RT group. The in-hospital deaths following surgery included three deaths in the NeoCF group, two deaths in the NeoCF+D group, and one in the NeoCF+RT group. INTERPRETATION: Neoadjuvant triplet chemotherapy followed by oesophagectomy resulted in a statistically significant overall survival benefit compared with doublet chemotherapy and might be the new standard of care for locally advanced OSCC who are in good condition in Japan. Neoadjuvant doublet chemotherapy plus radiotherapy did not show significant improvement of survival compared with doublet chemotherapy. FUNDING: Japan Agency for Medical Research and Development and National Cancer Center Research and Development Fund.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Cisplatin , Docetaxel , Esophageal Neoplasms , Fluorouracil , Neoadjuvant Therapy , Humans , Middle Aged , Esophageal Neoplasms/therapy , Esophageal Neoplasms/pathology , Esophageal Neoplasms/mortality , Male , Female , Neoadjuvant Therapy/methods , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Fluorouracil/administration & dosage , Fluorouracil/therapeutic use , Aged , Cisplatin/administration & dosage , Cisplatin/therapeutic use , Docetaxel/administration & dosage , Docetaxel/therapeutic use , Adult , Esophageal Squamous Cell Carcinoma/therapy , Esophageal Squamous Cell Carcinoma/pathology , Esophageal Squamous Cell Carcinoma/mortality , Chemoradiotherapy/methods , EsophagectomyABSTRACT
BACKGROUND: It remains unclear which patients with biochemical recurrence after prostatectomy are most suitable for salvage radiotherapy. We evaluated the parameters related to outcomes. METHODS: We retrospectively evaluated patients who underwent salvage therapy for biochemical recurrence after prostatectomy between 2005 and 2019. This study aimed to evaluate biochemical recurrence-free survival (bRFS) after salvage radiotherapy and elucidate the parameters associated with bRFS. The bRFS rate was calculated using the Kaplan-Meier method, and the parameters associated with bRFS were evaluated using Cox regression analysis. RESULTS: This study included 67 patients treated with salvage radiotherapy with a median age of 67 years at salvage radiotherapy. The median follow-up period after salvage radiotherapy was 7.3 years. The 5-year bRFS rate following salvage radiotherapy was 47.1%. Univariate analysis showed that PSA doubling time < 6 months, positive surgical margin, and pathological Gleason score ≥ 8 were significantly associated with shorter bRFS (p < 0.001, p = 0.036, p = 0.047, respectively). Multivariable analysis showed that a PSA doubling time < 6 months and positive surgical margins were significantly associated with shorter bRFS (p = 0.001 and p = 0.018, respectively). No serious adverse events were observed. CONCLUSIONS: In our hospital, approximately half of the patients are under long-term control with salvage radiotherapy. A PSA doubling time of < 6 months and positive surgical margins were suggested to be associated with poor outcomes of salvage radiotherapy.
Subject(s)
Neoplasm Recurrence, Local , Prostate-Specific Antigen , Prostatectomy , Prostatic Neoplasms , Salvage Therapy , Humans , Male , Salvage Therapy/methods , Prostatectomy/methods , Prostatic Neoplasms/radiotherapy , Prostatic Neoplasms/surgery , Prostatic Neoplasms/pathology , Prostatic Neoplasms/blood , Aged , Retrospective Studies , Middle Aged , Neoplasm Recurrence, Local/radiotherapy , Prostate-Specific Antigen/blood , Neoplasm Grading , Disease-Free Survival , Margins of ExcisionABSTRACT
BACKGROUND: First-line nivolumab plus chemotherapy and nivolumab plus ipilimumab both demonstrated significant overall survival (OS) benefit versus chemotherapy in previously untreated patients with advanced esophageal squamous cell carcinoma (ESCC) in the CheckMate 648 trial, leading to approvals of both nivolumab-containing regimens in many countries. We report longer-term follow-up data. METHODS: This open-label, phase III trial (NCT03143153) enrolled adults with previously untreated, unresectable, advanced, recurrent, or metastatic ESCC. Patients were randomized 1:1:1 to nivolumab plus chemotherapy, nivolumab plus ipilimumab, or chemotherapy. Primary endpoints were OS and progression-free survival (PFS) by blinded independent central review. Hierarchical testing was performed first in patients with tumor cell programmed death ligand 1 (PD-L1) expression of ≥1% and then in the overall population. RESULTS: A total of 970 patients were randomly assigned. After 29 months of minimum follow-up, nivolumab plus chemotherapy continued to demonstrate improvement in OS versus chemotherapy (hazard ratio [HR] = 0.59 [95% CI: 0.46-0.76]) in patients with tumor cell PD-L1 expression of ≥1% and in the overall population (HR = 0.78 [95% CI: 0.65-0.93]) and with nivolumab plus ipilimumab versus chemotherapy (HR = 0.62 [95% CI: 0.48-0.80]) in patients with tumor cell PD-L1 expression of ≥1% and in the overall population (HR = 0.77 [95% CI: 0.65-0.92]). In patients with tumor cell PD-L1 expression of ≥1%, nivolumab plus chemotherapy demonstrated PFS benefit versus chemotherapy (HR = 0.67 [95% CI: 0.51-0.89]); PFS benefit was not observed with nivolumab plus ipilimumab versus chemotherapy (HR = 1.04 [95% CI: 0.79-1.36]). Among all treated patients (n = 936), Grade 3-4 treatment-related adverse events were reported in 151 (49%, nivolumab plus chemotherapy), 105 (32%, nivolumab plus ipilimumab), and 110 (36%, chemotherapy) patients. CONCLUSIONS: Nivolumab plus chemotherapy and nivolumab plus ipilimumab continued to demonstrate clinically meaningful OS benefit versus chemotherapy with no new safety signals identified with longer follow-up, further supporting use as first-line standard treatment options for patients with advanced ESCC.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Ipilimumab , Nivolumab , Humans , Ipilimumab/administration & dosage , Ipilimumab/therapeutic use , Ipilimumab/adverse effects , Nivolumab/administration & dosage , Nivolumab/therapeutic use , Male , Esophageal Squamous Cell Carcinoma/drug therapy , Esophageal Squamous Cell Carcinoma/mortality , Esophageal Squamous Cell Carcinoma/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Female , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/pathology , Esophageal Neoplasms/mortality , Middle Aged , Aged , Follow-Up Studies , Adult , Progression-Free Survival , B7-H1 Antigen/metabolism , Aged, 80 and overABSTRACT
The prognostic significance of inflammation, immune response and nutritional status in patients with cancer is well-documented. The advanced lung cancer inflammation index (ALI) has emerged as a novel prognostic indicator, reflecting both inflammation and nutritional status. This study aimed to assess the prognostic relevance of preoperative ALI in patients with gastric cancer (GC). Data of 459 patients who underwent curative gastrectomy for GC between December 2013 and November 2017 at the Kanagawa Cancer Center (Yokohama, Japan) were retrospectively analyzed. Preoperative ALI was calculated from blood tests. Patients were divided into the high- and low-ALI groups. This study investigated the association between preoperative ALI, clinicopathological features, overall survival (OS) and relapse-free survival (RFS) after propensity-matched analysis. Comparative analysis revealed that patients in the low-ALI group tended to be older, were predominantly female, had lower body mass index and had a higher incidence of lymphatic invasion compared with those in the high-ALI group before propensity-matched analysis. Notably, the low-ALI group exhibited significantly reduced OS and RFS post-gastrectomy (85.5% vs. 93.8%, P=0.01; and 82.1% vs. 91.8%, P=0.02, respectively). Multivariate analysis identified low ALI as an independent prognostic factor for both OS and RFS. In conclusion, preoperative ALI could provide a valuable prognostic tool for patients with GC undergoing curative resection, offering insights into patient survival outcomes based on their inflammatory and nutritional status.
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BACKGROUND/AIM: In East Asia, the standard treatment for resectable advanced gastric cancer involves gastrectomy and postoperative adjuvant chemotherapy; nevertheless, neoadjuvant chemotherapy is also expected to improve survival rates. However, it remains unclear whether the same criteria can be used to select adjuvant chemotherapy for patients treated with neoadjuvant chemotherapy, or how survival varies between post-chemotherapy pathological Stage (ypStage) and pathological Stage without chemotherapy (pStage). This study evaluated the long-term outcomes of ypStage and pStage in gastric cancers and investigated the optimal intensity of adjuvant chemotherapy for patients who have received preoperative chemotherapy. PATIENTS AND METHODS: From January 2007 to November 2019, 1,585 patients underwent radical gastrectomy for gastric cancer at the Kanagawa Cancer Center. The patient background was adjusted by propensity score matching, and recurrence-free survival was compared between the two groups. In addition, a prognostic factor analysis was conducted for each yp/pStage. RESULTS: The 5-year recurrence-free survival rates for yp/pStage I were 77.1% and 90.9%, respectively, with no significant difference (p=0.342). The 5-year recurrence-free survival rates for yp/pStage II were 50.4% and 69.1%, respectively, with no significant difference (p=0.062). The 5-year recurrence-free survival rates for yp/pStage III were 42.9% and 68.7%, respectively, with a significant difference observed (p=0.016). In the prognostic factor analysis for each stage, the presence or absence of preoperative chemotherapy was selected as an independent prognostic factor for yp/pStage I [hazard ratio (HR)=17.72; p=0.001] and yp/pStage II (HR=2.655, p=0.003). CONCLUSION: ypStage tends to have a worse prognosis than pStage, and further development of multidisciplinary treatment is necessary.
Subject(s)
Gastrectomy , Neoplasm Staging , Stomach Neoplasms , Humans , Stomach Neoplasms/pathology , Stomach Neoplasms/mortality , Stomach Neoplasms/surgery , Stomach Neoplasms/drug therapy , Male , Female , Middle Aged , Aged , Chemotherapy, Adjuvant , Prognosis , Neoadjuvant Therapy , Survival Rate , Retrospective Studies , AdultABSTRACT
BACKGROUND: First-line pembrolizumab plus chemotherapy (pembrolizumab-chemotherapy) demonstrated improved efficacy and a manageable safety profile versus placebo plus chemotherapy (placebo-chemotherapy) in the subgroup analysis of Japanese patients with advanced/metastatic esophageal cancer in KEYNOTE-590 at a median follow-up of 24.4 months. Longer-term data from the Japanese subgroup analysis of KEYNOTE-590 are reported. METHODS: Patients were randomly assigned 1:1 to pembrolizumab 200 mg or placebo every 3 weeks for ≤ 35 cycles plus chemotherapy (cisplatin 80 mg/m2 and 5-fluorouracil 800 mg/m2/day). Endpoints included overall survival (OS) and progression-free survival (PFS; investigator-assessed per RECIST v1.1; dual primary) and safety (secondary). Early tumor shrinkage (ETS) and depth of response (DpR) were assessed post hoc. RESULTS: Overall, 141 patients were enrolled in Japan. As of July 9, 2021, median follow-up was 36.6 months (range, 29.8-45.7). Pembrolizumab-chemotherapy showed a trend toward favorable OS (hazard ratio [HR], 0.70; 95% confidence interval [CI] 0.47-1.03) and PFS (0.57; 0.39-0.83) versus placebo-chemotherapy. In the pembrolizumab-chemotherapy group, patients with ETS ≥ 20% (55/74; 74.3%) versus < 20% (19/74; 25.7%) had favorable OS (HR, 0.23; 95% CI 0.12-0.42) and PFS (0.24; 0.13-0.43). Patients with DpR ≥ 60% (31/74; 41.9%) versus < 60% (43/74; 58.1%) had favorable OS (HR, 0.37; 95% CI 0.20-0.68) and PFS (0.24; 0.13-0.43). Grade 3-5 treatment-related adverse events occurred in 55/74 patients (74.3%) with pembrolizumab-chemotherapy and 41/67 patients (61.2%) with placebo-chemotherapy. CONCLUSIONS: With longer-term follow-up of Japanese patients with advanced/metastatic esophageal cancer, efficacy continued to favor pembrolizumab-chemotherapy compared with placebo-chemotherapy, with no new safety signals observed. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03189719.
Subject(s)
Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols , Cisplatin , Esophageal Neoplasms , Fluorouracil , Humans , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/pathology , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/adverse effects , Male , Female , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Aged , Follow-Up Studies , Japan/epidemiology , Cisplatin/administration & dosage , Cisplatin/therapeutic use , Fluorouracil/administration & dosage , Fluorouracil/therapeutic use , Progression-Free Survival , Adult , Treatment Outcome , Double-Blind Method , Neoplasm Metastasis , Antineoplastic Agents, Immunological/therapeutic use , Antineoplastic Agents, Immunological/administration & dosage , Antineoplastic Agents, Immunological/adverse effects , East Asian PeopleABSTRACT
Purpose: We retrospectively investigated spatial pattern associations between primary and recurrent tumor sites after definitive external-beam radiation therapy (EBRT) for prostate cancer, using positron emission tomography/computed tomography (PET/CT) with a prostate-specific membrane antigen (PSMA)-targeted probe, 18F-FSU-880. Methods and Materials: We used data from our prior phase 2 trial involving patients who received PET/CT with 18F-FSU-880, which was designed to evaluate the tumor detection efficacy of PSMA-PET/CT for recurrent prostate cancer. Data from patients with local intraprostatic recurrence detected by PSMA-PET/CT after definitive EBRT were retrospectively analyzed. The prostate and seminal vesicles were divided into 14 sections. Two diagnostic radiologists separately re-evaluated the intraprostatic location of the primary tumor on magnetic-resonance imaging and that of the recurrent tumor on PSMA-PET/CT, respectively, and the rate of overlap between primary and recurrent tumors was calculated. The overlap rate was defined as "the number of sections that overlapped between the primary tumor and recurrent tumor" divided by "the total number of sections of recurrent tumor". A recurrent tumor was considered to be at the same location as the primary tumor when the overlap rate was equal to or greater than 75%, and a partial overlap was defined as an overlap rate between 25 and 74%. Results: Twelve patients had local recurrence detected by PSMA-PET/CT. The median time to diagnosis of local recurrence was 9.1 (range, 2.2-12.3) years after definitive EBRT. The recurrent tumor was detected at the same location in 25.0%, and a partial overlap was noted in 41.7%. Conclusions: Local intraprostatic recurrence after definitive EBRT often occurs at the same site or at a partially overlapping site adjacent to the primary intraprostatic dominant lesion. Our results support the merit of focal dose-escalation for intraprostatic dominant lesions in definitive EBRT.
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BACKGROUND/AIM: Recently, preoperative inflammatory, immune, and nutritional statuses have attracted attention as prognostic factors in post-curative gastrectomy patients with gastric cancer (GC). The usefulness of the C-reactive protein-albumin-lymphocyte (CALLY) index as a prognostic factor in patients with various cancers, has been reported. However, reports on the clinical significance of the CALLY index in patients with GC after gastrectomy remain inadequate. In this prospective study, we focused on the preoperative CALLY index and investigated its usefulness as a prognostic factor in patients with GC. PATIENTS AND METHODS: This study included 459 patients who underwent gastrectomy for GC between December 2013 and November 2017 at Kanagawa Cancer Center, Kanagawa, Japan. The preoperative CALLY index was calculated based on the preoperative blood test data. Patients were divided into high- and low-CALLY groups. The associations of the preoperative CALLY scores with clinicopathological factors, overall survival (OS), and recurrence-free survival (RFS) after gastrectomy for GC were evaluated. RESULTS: The low-CALLY group was significantly older, had higher venous invasion, and a more progressive pStage than did the high-CALLY group. OS and RFS after gastrectomy in the low-CALLY group were significantly worse than those in the high-CALLY group (77.9% vs. 88.9%; p<0.001 and 73.8% vs. 87.1%; p<0.001, respectively). In the multivariate analysis, a low CALLY score was an independent prognostic factor of worse OS and RFS. CONCLUSION: Preoperative CALLY levels may be a useful prognostic predictor in patients with GC after curative gastrectomy.
Subject(s)
C-Reactive Protein , Stomach Neoplasms , Humans , Stomach Neoplasms/pathology , Prospective Studies , Prognosis , Lymphocytes/pathology , Gastrectomy/adverse effects , Retrospective StudiesABSTRACT
BACKGROUND/AIM: Radical resection after preoperative adjuvant chemotherapy (NAC) is a standard treatment for patients with locally advanced esophageal squamous cell carcinoma (LAESCC), but its outcome remains unsatisfactory. In order to develop a personalized treatment program for LAES, we herein compared the survival prediction utility of five pre-NAC nutritional, inflammatory, and immune indexes in patients with LAESCC. PATIENTS AND METHODS: We evaluated the survival of 203 patients with LAESCC who underwent radical resection after NAC from January 2011 to September 2019 for the following representative pre-NAC nutritional, inflammatory, and immune indices: modified Glasgow Prognostic Score, Prognostic Nutritional Index, C-reactive protein/albumin ratio, serum neutrophil/lymphocyte ratio, and Geriatric Nutrition Risk Index (GNRI) were evaluated for their impact on survival. RESULTS: Of the five indices, GNRI was the best predictor of survival as determined by the area under the curve (p<0.05). When patients were divided into three groups according to the nutritional risk assessment of Bouillanne et al. using the pre-NAC GNRI, the 5-year overall survival (OS) and recurrence-free survival (RFS) were significantly stratified (p<0.001). On multivariate analysis, the GNRI independently identified a poor OS group [group 1: hazard ratio (HR)=2.598, p=0.002; group 2: HR=6.257, p<0.001] and a high recurrence risk group (group 1: HR=1.967, p=0.016; group 2: HR=4.467, p<0.001). CONCLUSION: In patients with LAESCC, GNRI may be the most accurate, reliable, and useful prognostic factor among the five major systemic inflammatory and nutritional indices.
Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Humans , Aged , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/surgery , Esophageal Neoplasms/pathology , Retrospective Studies , Nutrition Assessment , Chemotherapy, Adjuvant , Prognosis , Risk FactorsABSTRACT
BACKGROUND/AIM: This study aimed to compare dietary intake (DI) after gastrectomy for gastric cancer between patients with (C group) and without (NC group) postoperative surgical complications. PATIENTS AND METHODS: This prospective observational study enrolled patients who underwent gastrectomy for gastric cancer. DI was assessed using a food frequency questionnaire with 82 food items (FFQW82) during nutritional counseling before surgery and at one and three months after surgery. RESULTS: A total of 225 patients participated in this study. Of the 225 patients, 193 had no postoperative complications, and 32 had postoperative complications (Clavien-Dindo grade ≥2). The median DI at 1 month postoperatively was 1508 kcal/day in the NC group and 1,470.5 kcal/day in the C group (p=0.175). The median DI at 3 months postoperatively was 1,623 kcal/day in the NC group and 1575 kcal/day in the C group (p=0.473). There was a significant difference between the NC and C groups in the rate of decrease in DI at one month (median: -8.44% vs. -15.37%, p=0.032) and at three months postoperatively (median: -3.58% vs. -6.12%, p=0.038). CONCLUSION: There was a statistically significant difference in the rate of decrease in DI after gastrectomy between the C and NC groups at 1 and 3 months postoperatively. Our results suggest that patients with postoperative surgical complications require additional nutritional treatment for decreased DI.
Subject(s)
Stomach Neoplasms , Humans , Stomach Neoplasms/complications , Postoperative Complications/etiology , Postoperative Complications/surgery , Gastrectomy/adverse effects , Gastrectomy/methods , Eating , Prospective Studies , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND/AIM: The tryptophanyl-tRNA synthetase 1 gene (WARS1), encodes a tryptophan-tRNA synthetase involved in the amino acidification of tryptophan-tRNA and has been reported to be involved in cancer cell growth, metastasis promotion, and drug resistance in a variety of cancers. This study investigated the clinical significance of WARS1 expression as a biomarker in gastric cancer tissues obtained from patients with locally advanced gastric cancer (GC) who underwent radical resection. PATIENTS AND METHODS: WARS1 expression in GC tissues and adjacent normal gastric mucosa of 253 patients with pStage II/III GC who underwent curative resection was determined using quantitative polymerase chain reaction (PCR). Association of WARS1 expression levels, categorized into high and low expression based on the median expression levels, with clinicopathological factors and overall survival (OS) of these patients was assessed. RESULTS: The low-WARS1 expression group had significantly higher serosal invasion, lymph node metastasis, lymphatic invasion, venous invasion, and pathological stage than did the high-WARS1 expression group. OS was significantly worse in the low- than in the high-WARS1 expression group (5-year survival 52.2% vs. 75.9%; p=0.0001). Furthermore, in multivariate analysis, low WARS1 expression was an independent predictor for poor OS (hazard ratio=2.101; 95% confidence interval=1.328-3.322; p=0.002). CONCLUSION: In patients with locally advanced GC, after curative resection, WARS1 expression in GC tissue may be a useful prognostic marker.
Subject(s)
Stomach Neoplasms , Tryptophan-tRNA Ligase , Humans , Stomach Neoplasms/genetics , Stomach Neoplasms/surgery , Stomach Neoplasms/pathology , Tryptophan-tRNA Ligase/genetics , Clinical Relevance , Tryptophan , Biomarkers, Tumor/genetics , Biomarkers, Tumor/analysis , Gene Expression , Prognosis , Neoplasm StagingABSTRACT
BACKGROUND: Tumor-associated antigen (TAA)-specific CD8(+) T cells are essential for nivolumab therapy, and irradiation has been reported to have the potential to generate and activate TAA-specific CD8(+) T cells. However, mechanistic insights of T-cell response during combinatorial immunotherapy using radiotherapy and nivolumab are still largely unknown. METHODS: Twenty patients included in this study were registered in the CIRCUIT trial (ClinicalTrials.gov, NCT03453164). All patients had multiple distant metastases and were intolerance or had progressed after primary and secondary chemotherapy without any immune checkpoint inhibitor. In the CIRCUIT trial, eligible patients were treated with a total of 22.5 Gy/5 fractions/5 days of radiotherapy to the largest or symptomatic lesion prior to receiving nivolumab every 2 weeks. In these 20 patients, T-cell responses during the combinatorial immunotherapy were monitored longitudinally by high-dimensional flow cytometry-based, multiplexed major histocompatibility complex multimer analysis using a total of 46 TAAs and 10 virus epitopes, repertoire analysis of T-cell receptor ß-chain (TCRß), together with circulating tumor DNA analysis to evaluate tumor mutational burden (TMB). RESULTS: Although most TAA-specific CD8(+) T cells could be tracked longitudinally, several TAA-specific CD8(+) T cells were detected de novo after irradiation, but viral-specific CD8(+) T cells did not show obvious changes during treatment, indicating potential irradiation-driven antigen spreading. Irradiation was associated with phenotypical changes of TAA-specific CD8(+) T cells towards higher expression of killer cell lectin-like receptor subfamily G, member 1, human leukocyte antigen D-related antigen, T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain, CD160, and CD45RO together with lower expression of CD27 and CD127. Of importance, TAA-specific CD8(+) T cells in non-progressors frequently showed a phenotype of CD45RO(+)CD27(+)CD127(+) central memory T cells compared with those in progressors. TCRß clonality (inverted Pielou's evenness) increased and TCRß diversity (Pielou's evenness and Diversity Evenness score) decreased during treatment in progressors (p=0.029, p=0.029, p=0.012, respectively). TMB score was significantly lower in non-progressors after irradiation (p=0.023). CONCLUSION: Oligo-fractionated irradiation induces an immune-modulating effect with potential antigen spreading and the combination of radiotherapy and nivolumab may be effective in a subset of patients with gastric cancer.
Subject(s)
Nivolumab , Stomach Neoplasms , Humans , Nivolumab/pharmacology , Nivolumab/therapeutic use , CD8-Positive T-Lymphocytes , Stomach Neoplasms/drug therapy , Stomach Neoplasms/metabolism , Immunity , Immunotherapy , Leukocyte Common AntigensABSTRACT
BACKGROUND/PURPOSE: The long-term clinical impact of prostate position-based image-guided radiotherapy (IGRT) for localized prostate cancer remains unclear. MATERIALS AND METHODS: We retrospectively compared clinical outcomes following intensity-modulated radiation therapy (IMRT) with cone-beam computed tomography-based prostate position-based IGRT (P-IGRT) or without P-IGRT (non-P-IGRT). From June 2011, we applied P-IGRT in IMRT for intermediate-risk (IR) prostate cancer (PCa) (D'Amico risk classification) (76 Gy in 38 fractions, with smaller margins). Clinical outcomes of patients who received P-IGRT between June 2011 and June 2019 were retrospectively compared with those of patients with IR PCa who received IMRT without P-IGRT between October 2002 and May 2011 in our institution (74 Gy in 37 fractions). RESULTS: A total of 222 consecutive patients were analyzed: 114 in the P-IGRT cohort and 108 in the non-P-IGRT cohort. The median follow-up period after IMRT was 7.1 years for the P-IGRT cohort and 10.8 years for the non-P-IGRT cohort. The biochemical failure-free rate was significantly better in the P-IGRT cohort (94.9% for the P-IGRT cohort vs 82.7% for the non-P-IGRT cohort at 10 years, p = 0.041). The rate of rectal bleeding which needs intervention including the use of suppositories was significantly lower in the P-IGRT cohort (p < 0.001). CONCLUSIONS: The use of P-IGRT with higher doses and smaller margins was correlated with significantly better biochemical control, and a lower incidence of rectal bleeding in IMRT for intermediate-risk prostate cancer. The enhanced accuracy using P-IGRT has the potential to independently improve disease control and reduce late rectal bleeding.
Subject(s)
Prostatic Neoplasms , Radiotherapy, Image-Guided , Radiotherapy, Intensity-Modulated , Male , Humans , Prostate , Radiotherapy, Intensity-Modulated/adverse effects , Retrospective Studies , Prostatic Neoplasms/radiotherapy , Radiotherapy, Image-Guided/adverse effectsABSTRACT
BACKGROUND/AIM: Chitinase-3-like protein 1 (CHI3L1), encoded by CHI3L1, is thought to be involved in growth, invasion, migration, and resistance to chemotherapy in cancer. This study aimed to investigate the clinical significance of CHI3L1 expression as a biomarker in gastric cancer (GC) tissues of patients with locally advanced GC after curative resection. PATIENTS AND METHODS: Quantitative polymerase chain reaction (PCR) was used to determined CHI3L1 expression in GC tissues and adjacent normal gastric mucosa of 253 patients with pStage II/III GC who underwent curative resection. We compared the expression levels in GC tissues and adjacent normal gastric mucosa, and examined the relationship between expression in GC tissues and clinicopathological factors and overall survival (OS) in these patients. RESULTS: CHI3L1 expression was significantly associated with lymph-node metastasis and venous invasion. OS rate was significantly lower in the high- than in the low-CHI3L1 expression group (5-year survival 55.5% vs. 72.6%; p=0.009). Furthermore, in multivariate analysis, high CHI3L1 gene expression was an independent factor for poor OS (hazard ratio=2.030; 95% confidence interval=1.318-3.127; p=0.001). CONCLUSION: In patients with locally advanced GC after curative resection, expression of the CHI3L1 in GC tissue may be a useful prognostic marker.
Subject(s)
Chitinase-3-Like Protein 1 , Stomach Neoplasms , Humans , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Chitinase-3-Like Protein 1/genetics , Clinical Relevance , Gene Expression , Neoplasm Staging , Prognosis , Stomach Neoplasms/genetics , Stomach Neoplasms/surgery , Stomach Neoplasms/metabolismABSTRACT
BACKGROUND/AIM: Pregnancy zone protein (PZP), encoded by PZP, belongs to the α-2-macroglobulin superfamily, and plays an important role in inflammatory responses and immune cell activation in cancer. However, the relationship between gastric cancer (GC) and PZP is poorly studied. This study investigated the clinical significance of PZP expression in GC tissues of patients with locally advanced GC after curative resection. PATIENTS AND METHODS: Using quantitative polymerase chain reaction, we measured PZP expression in GC tissues and adjacent normal gastric mucosa of 253 patients with pStage II/III GC who underwent curative resection. We compared the expression levels of PZP in GC tissues and adjacent normal gastric mucosa and examined the relationship of PZP expression in GC tissues with clinicopathological factors and overall survival (OS). RESULTS: PZP expression was significantly associated with histology, venous invasion, and pathological stage. The high PZP expression group had significantly worse OS than did the low expression group (5-year survival 48.6% vs. 68.5%, p=0.0003). Furthermore, in multivariate analysis, high PZP expression was an independent factor for poor OS (hazard ratio=1.984, 95% confidence interval=1.307-3.012, p=0.0013). CONCLUSION: In post-curative resection patients with locally advanced GC, PZP expression in GC tissue may be a useful prognostic marker.
Subject(s)
Pregnancy Proteins , Stomach Neoplasms , Humans , Clinical Relevance , Gastrectomy , Prognosis , Stomach Neoplasms/pathology , Pregnancy Proteins/geneticsABSTRACT
BACKGROUND/AIM: The asialoglycoprotein receptor 2 gene (ASGR2) encodes a subunit of the asialoglycoprotein receptor, a transmembrane protein, which has recently been reported to be involved in gastric cancer (GC) progression. This study aimed to investigate the clinical significance of ASGR2 expression in GC tissues of patients with locally advanced gastric cancer (LAGC) after curative resection. PATIENTS AND METHODS: ASGR2 expression was measured in GC tissues and adjacent normal gastric mucosa in 253 patients with pStage II/III GC who underwent curative resection, by using quantitative polymerase chain reaction. We compared the expression levels in GC tissues and adjacent normal stomach mucosa, and evaluated the relationship of its expression in GC tissues with clinicopathological factors and overall survival (OS). RESULTS: ASGR2 expression was significantly associated with lymph node metastasis and venous invasion. The high ASGR2-expression group demonstrated significantly lower survival than the low expression group (5-year survival 55.5% vs. 72.6%; p=0.009). Furthermore, in multivariate analysis, high ASGR2 expression was an independent factor for poor OS (hazard ratio=2.030; 95% confidence interval=1.318-3.127; p=0.001). CONCLUSION: ASGR2 expression in GC tissues may be a useful prognostic marker in patients with LAGC after curative resection.