Long-term survivals of immune checkpoint inhibitors as neoadjuvant and adjuvant therapy in dMMR/MSI-H colorectal and gastric cancers.

BACKGROUND: The long-term survival benefit of immune checkpoint inhibitors (ICIs) in neoadjuvant and adjuvant settings is unclear for colorectal cancers (CRC) and gastric cancers (GC) with deficiency of mismatch repair (dMMR) or microsatellite instability-high (MSI-H). METHODS: This retrospective study enrolled patients with dMMR/MSI-H CRC and GC who received at least one dose of neoadjuvant ICIs (neoadjuvant cohort, NAC) or adjuvant ICIs (adjuvant cohort, AC) at 17 centers in China. Patients with stage IV disease were also eligible if all tumor lesions were radically resectable. RESULTS: In NAC (n = 124), objective response rates were 75.7% and 55.4%, respectively, in CRC and GC, and pathological complete response rates were 73.4% and 47.7%, respectively. The 3-year disease-free survival (DFS) and overall survival (OS) rates were 96% (95%CI 90-100%) and 100% for CRC (median follow-up [mFU] 29.4 months), respectively, and were 84% (72-96%) and 93% (85-100%) for GC (mFU 33.0 months), respectively. In AC (n = 48), the 3-year DFS and OS rates were 94% (84-100%) and 100% for CRC (mFU 35.5 months), respectively, and were 92% (82-100%) and 96% (88-100%) for GC (mFU 40.4 months), respectively. Among the seven patients with distant relapse, four received dual blockade of PD1 and CTLA4 combined with or without chemo- and targeted drugs, with three partial response and one progressive disease. CONCLUSION: With a relatively long follow-up, this study demonstrated that neoadjuvant and adjuvant ICIs might be both associated with promising DFS and OS in dMMR/MSI-H CRC and GC, which should be confirmed in further randomized clinical trials.

Multimodal Therapy Versus Primary Surgery for Gastric and Gastroesophageal Junction Diffuse Type Carcinoma, with a Focus on Signet Ring Cell Carcinoma: A Nationwide Study.

BACKGROUND: Diffuse type adenocarcinoma and, more specifically, signet ring cell carcinoma (SRCC) of the stomach and gastroesophageal junction (GEJ) have a poor prognosis and the value of neoadjuvant chemo(radio)therapy (nCRT) is unclear. METHODS: All patients who underwent surgery for diffuse type gastric and GEJ carcinoma between 2004 and 2015 were retrospectively included from the Netherlands Cancer Registry. The primary outcome was overall survival after surgery. Kaplan-Meier curves were plotted. Furthermore, multivariable Poisson and Cox regressions were performed, correcting for confounders. To comply with the Cox regression proportional hazard assumption, gastric cancer survival was split into two groups, i.e. <90 days and >90 days, postoperatively by adding an interaction variable. RESULTS: Analyses included 2046 patients with diffuse type cancer: 1728 gastric cancers (50% SRCC) and 318 GEJ cancers (39% SRCC). In the gastric cancer group, 49% received neoadjuvant chemotherapy (nCT) and 51% received primary surgery (PS). All-cause mortality within 90 days postoperatively was lower after nCT (hazard ratio [HR] 0.29, 95% confidence interval [CI] 0.20-0.44; p < 0.001). Also after 90 days, mortality was lower in the nCT group (HR for the interaction variable 2.84, 95% CI 1.87-4.30, p < 0.001; total HR 0.29*2.84 = 0.84). In the GEJ group, 38% received nCT, 22% received nCRT, and 39% received PS. All-cause mortality was lower after nCT (HR 0.63, 95% CI 0.43-0.93; p = 0.020) compared with PS. The nCRT group was removed from the Cox regression analysis since the Kaplan-Meier curves of nCRT and PS intersected. The results for gastric and GEJ carcinomas were similar between the SRCC and non-SRCC subgroups. CONCLUSION: For gastric and GEJ diffuse type cancer, including SRCC, nCT was associated with increased survival.

The Comparison of FLOT and DCF Regimens as Perioperative Treatment for Gastric Cancer.

INTRODUCTION: Locoregional gastric cancer is a still serious problem and perioperative treatments may improve the success of management. Different regimens were examined. The present study purposed to compare the efficacy of fluorouracil-leucovorin-oxaliplatin-docetaxel (FLOT) and docetaxel-cisplatin-fluorouracil (DCF) regimens. METHODS: A retrospective multicenter study assessed the patients with locoregional gastric cancer. There are 240 patients (137 DCF, 103 FLOT). Survival rates were compared. RESULTS: Demographic features were similar between the two groups, but the time period was different. The FLOT group had 7.8% pathological complete response, while the DCF group did not. Disease-free survival was longer in the FLOT than in the DCF group (median not reached - 13.94 months, respectively). Median overall survival was similar (30.9 vs. 37.8 months), but median follow-up affected the analysis. Survival for 36 months was 63% for the FLOT group and 40% for the DCF group (log-rank; p = 0.015). CONCLUSION: FLOT regimen was superior to DCF regimen for response and survival rates. DCF is a historical approach. Long-term follow-up period is needed for FLOT treatment.

Development of perioperative immune checkpoint inhibitor therapy for locally advanced esophageal squamous cell carcinoma.

The standard preoperative treatment for resectable locally advanced esophageal squamous cell carcinoma (ESCC) is chemoradiotherapy in western countries (based on the CROSS trial) and triplet chemotherapy in Japan (based on the JCOG1109 trial). Postoperative nivolumab has recently been shown to improve disease-free survival in resectable locally advanced esophageal cancer after preoperative chemoradiotherapy in patients who had residual pathological disease, based on the CheckMate 577 trial. Furthermore, preoperative immune checkpoint inhibitor-containing treatments have also been developed. The JCOG1804E trial is presently evaluating the safety and efficacy of preoperative nivolumab-containing chemotherapy for resectable locally advanced ESCC. This review discusses the treatment of resectable locally advanced ESCC and future perspectives on perioperative immune checkpoint inhibitor-containing treatments.

[Box: see text].

Perioperative FLOT plus ramucirumab for resectable esophagogastric adenocarcinoma: A randomized phase II/III trial of the German AIO and Italian GOIM.

This multicenter, randomized phase II/III study evaluated the addition of the vascular endothelial growth factor receptor-2 inhibitor ramucirumab to FLOT as perioperative treatment for resectable esophagogastric adenocarcinoma. Patients received either FLOT alone (Arm A) or combined with ramucirumab followed by ramucirumab monotherapy (Arm B). The primary endpoint for the phase II portion was the pathological complete or subtotal response (pCR/pSR) rate. Baseline characteristics were comparable between both arms with a high rate of tumors signet-ring cell component (A:47% B:43%). No between-arm difference in pCR/pSR rate was seen (A:29% B:26%), therefore the transition to phase III was not pursued. Nevertheless, the combination was associated with a significantly increased R0-resection rate compared with FLOT alone (A:82% B:96%; P = .009). In addition, the median disease-free survival was numerically improved in Arm B (A:21 months B:32 months, HR 0.75, P = 0.218), while the median overall survival was similar in both treatment arms (A:45 months B:46 months, HR 0.94, P = 0.803). Patients with Siewert type I tumors receiving transthoracic esophagectomy with intrathoracic anastomosis showed an increased risk of serious postoperative complications after ramucirumab treatment, therefore recruitment of those patients was stopped after the first-third of the study. Overall, surgical morbidity and mortality was comparable, whereas more non-surgical grade ≥ 3 adverse events were observed with the combination, especially anorexia (A:1% B:11%), hypertension (A:4% B:13%) and infections (A:19% B:33%). The combination of ramucirumab and FLOT as perioperative treatment shows efficacy signals, particularly in terms of R0 resection rates, for a study population with a high proportion of prognostically poor histological subtypes, and further evaluation in this subgroup seems warranted.

Perioperative or only adjuvant gemcitabine plus nab-paclitaxel for resectable pancreatic cancer (NEONAX)-a randomized phase II trial of the AIO pancreatic cancer group.

BACKGROUND: Data on perioperative chemotherapy in resectable pancreatic ductal adenocarcinoma (rPDAC) are limited. NEONAX examined perioperative or adjuvant chemotherapy with gemcitabine plus nab-paclitaxel in rPDAC (National Comprehensive Cancer Network criteria). PATIENTS AND METHODS: NEONAX is a prospective, randomized phase II trial with two independent experimental arms. One hundred twenty-seven rPDAC patients in 22 German centers were randomized 1 : 1 to perioperative (two pre-operative and four post-operative cycles, arm A) or adjuvant (six cycles, arm B) gemcitabine (1000 mg/m2) and nab-paclitaxel (125 mg/m2) on days 1, 8 and 15 of a 28-day cycle. RESULTS: The primary endpoint was disease-free survival (DFS) at 18 months in the modified intention-to-treat (ITT) population [R0/R1-resected patients who started neoadjuvant chemotherapy (CTX) (A) or adjuvant CTX (B)]. The pre-defined DFS rate of 55% at 18 months was not reached in both arms [A: 33.3% (95% confidence interval [CI] 18.5% to 48.1%), B: 41.4% (95% CI 20.7% to 62.0%)]. Ninety percent of patients in arm A completed neoadjuvant treatment, and 42% of patients in arm B started adjuvant chemotherapy. R0 resection rate was 88% (arm A) and 67% (arm B), respectively. Median overall survival (mOS) (ITT population) as a secondary endpoint was 25.5 months (95% CI 19.7-29.7 months) in arm A and 16.7 months (95% CI 11.6-22.2 months) in the upfront surgery arm. This difference corresponds to a median DFS (mDFS) (ITT) of 11.5 months (95% CI 8.8-14.5 months) in arm A and 5.9 months (95% CI 3.6-11.5 months) in arm B. Treatment was safe and well tolerable in both arms. CONCLUSIONS: The primary endpoint, DFS rate of 55% at 18 months (mITT population), was not reached in either arm of the trial and numerically favored the upfront surgery arm B. mOS (ITT population), a secondary endpoint, numerically favored the neoadjuvant arm A [25.5 months (95% CI 19.7-29.7months); arm B 16.7 months (95% CI 11.6-22.2 months)]. There was a difference in chemotherapy exposure with 90% of patients in arm A completing pre-operative chemotherapy and 58% of patients starting adjuvant chemotherapy in arm B. Neoadjuvant/perioperative treatment is a novel option for patients with resectable PDAC. However, the optimal treatment regimen has yet to be defined. The trial is registered with ClinicalTrials.gov (NCT02047513) and the European Clinical Trials Database (EudraCT 2013-005559-34).

Targeted Therapy in Early Stage Non-small Cell Lung Cancer.

OPINION STATEMENT: Tyrosine kinase inhibitors (TKIs) have dramatically improved tumor response rates and survival benefits in advanced oncogenic non-small-cell lung cancer (NSCLC). Given the impressive success, a renewed interest has been raised in the study of these agents in the perioperative setting. Preliminary data have shown dramatic effectiveness compared to conventional chemotherapy. Given the explicit need to induce durable responses and raise cure rates, we summarize the current progression, identify key challenges, and raise potential opportunities for perioperative targeted therapy that range from precise biomarkers to optimal adjuvant regimens for individual patients. As perioperative treatment indeed provides researchers with a unique platform to address the challenges mentioned above, investigators could obtain a comprehensive analysis of genomic profiling and trace resistance mechanisms. Multidisciplinary collaboration and adaptive clinical trial designs are warranted to integrate translational research into personalized perioperative TKI treatment paradigms.

Surgical and perioperative treatment strategy for resectable esophagogastric junction cancer.

Esophagogastric junction cancer is defined as adenocarcinoma with the epicenter within 5 cm of the esophagogastric junction in the West according to the Siewert classification. In contrast, it is defined as cancer of any histological type with the epicenter located within 2 cm proximal or distal to the esophagogastric junction in Japan according to the Nishi classification. Recently, the incidence of esophagogastric junction cancer has been rapidly rising all over the world, leading to much attention. Esophagogastric junction cancer was previously treated like gastric cancer or esophageal cancer because it is a less frequently occurring tumor. Esophagogastric junction cancer is considered to have worse prognosis than gastric cancer. Therefore, in recent years, esophagogastric junction cancer has been recognized as an independent malignant disease with poor prognosis, and thus development of treatment strategies focused on esophagogastric junction cancer is needed. The mapping of frequent metastasis in the mediastinal and abdominal lymph nodes has revealed the lymphatic flow from esophagogastric junction cancer specifically, establishing the optimal lymph node dissection area and surgical approach. The development of multimodal treatment that includes chemotherapy, radiotherapy and immunotherapy has been applied to improve the survival of esophagogastric junction cancer. In this review, we summarize clinical trials with important evidence on surgical and multimodal perioperative treatments for esophagogastric junction cancer.

Prognostic factors of perioperative FLOT regimen in operable gastric and gastroesophageal junction tumors: real-life data (Turkish Oncology Group).

BACKGROUND: Perioperative FLOT regimen is a standard of care in locally advanced operable gastric and GEJ adenocarcinoma. We aimed to determine the efficacy, prognostic factors of perioperative FLOT chemotherapy in real-life gastric and GEJ tumors. METHODS: The data of patients who were treated with perioperative FLOT chemotherapy were retrospectively analyzed from 34 different oncology centers in Turkey. Baseline clinical and demographic characteristics, pretreatment laboratory values, histological and molecular characteristics were recorded. RESULTS: A total of 441 patients were included in the study. The median of age our study population was 60 years. The majority of patients with radiological staging were cT3-4N(+) (89.9%, n = 338). After median 13.5 months (IQR: 8.5-20.5) follow-up, the median overall survival was NR (95% CI, NR to NR), and median disease free survival was 22.9 (95% CI, 18.6 to 27.3) months. The estimated overall survival at 24 months was 62%. Complete pathological response (pCR) and near pCR was achieved in 23.8% of all patients. Patients with lower NLR or PLR have significantly longer median OS (p = 0.007 and p = 0.033, respectively), and patients with lower NLR have significantly longer median DFS (p = 0.039), but PLR level did not affect DFS (p = 0.062). The OS and DFS of patients with better ECOG performance scores and those who could receive FLOT as adjuvant chemotherapy instead of other regimens were found to be better. NLR was found to be independent prognostic factor for OS in the multivariant analysis. At least one adverse event reported in 57.6% of the patients and grade 3-4 toxicity was seen in 23.6% patients. DISCUSSION: Real-life perioperative FLOT regimen in operable gastric and GEJ tumors showed similar oncologic outcomes compared to clinical trials. Better performance status, receiving adjuvant chemotherapy as same regimen, low grade and low NLR and PLR improved outcomes in real-life. However, in multivariate analysis, only NLR affected OS.

Trastuzumab in combination with 5-fluorouracil, leucovorin, oxaliplatin and docetaxel as perioperative treatment for patients with human epidermal growth factor receptor 2-positive locally advanced esophagogastric adenocarcinoma: A phase II trial of the Arbeitsgemeinschaft Internistische Onkologie Gastric Cancer Study Group.

Perioperative chemotherapy with 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) is a mainstay in the treatment of esophagogastric adenocarcinomas (EGA). Trastuzumab improved survival when added to chemotherapy in patients with HER-2-positive metastatic EGA. We investigated the combination of trastuzumab and FLOT as perioperative treatment in patients with locally advanced EGA. A multicenter phase II study evaluated the efficacy and toxicity of perioperative FLOT (24-hours 5-FU 2600 mg/m2 , leucovorin 200 mg/m2 , oxaliplatin 85 mg/mg2 , docetaxel 50 mg/m2 , trastuzumab 6 mg/kg then 4 mg/kg d1, repeated d15 for four cycles preoperatively and postoperatively followed by 9 cycles of trastuzumab monotherapy) in patients with HER-2 positive EGA. Patients had ≥cT2, any N, M0 EGA. The primary endpoint was the rate of centrally assessed pathological complete response (pCR). Secondary endpoints comprised disease-free (DFS) and overall survival (OS), R0 resection rate, toxicity and surgical morbidity. Fifty-six evaluable patients (median age 62 years) were included; n = 40 had tumors originating from the esophagogastric junction; T stage was (cT2/3/4/unknown): 4/42/8/2; n = 50 patients had cN+ disease. Main adverse events grades 3-4: leukopenia (17.9%), neutropenia (46.6%) and diarrhea (17.0%). All patients underwent tumor resections. R0 resection rate was 92.9%. Eight patients had anastomotic leakage. One postoperative death occurred. pCR was found in 12 patients (21.4%) and a further n = 14 patients (25.0%) had near complete response. Median DFS was 42.5 months and the 3-year OS rate was 82.1%. The primary endpoint of achieving a pCR >20% was reached. No unexpected safety issues were observed. Survival data are promising.

Perioperative Management of Diabetes Mellitus: Novel Approaches.

PURPOSE OF REVIEW: Several studies have demonstrated the benefits of glycemic control in the perioperative period and there is ongoing interest in development of systematic approaches to achieving glycemic control. This review discusses currently available data and proposes a new approach to the management of hyperglycemia in the perioperative period. RECENT FINDINGS: In a recent study, we demonstrated that early preoperative identification of patients with poorly controlled diabetes and proactive treatment through various phases of surgery improves glycemic control, lowers the risk of surgical complications, and decreases the length of hospital stay. Implementation of a perioperative diabetes program that systematically identifies and treats patients with poor glycemic control early in the preoperative period is feasible and improves clinical care of patients undergoing elective surgery.

[History, current situation and bottleneck of the diagnosis and treatment system of hepatic hilar cholangiocarcinoma in Japan].

Hilar cholangiocarcinoma is one of the most difficult malignant tumors to treat in the biliary system. In Japan, 5-year survival rate of the disease has increased from 32.5% to 67.1% during the past 30 years. The impressive progress reflects the solid efforts in preoperative endoscopic diagnosis, innovation in surgery such as PTPE as well as hepato-pancreatoduodenectomy and perioperative treatment including replacement of the bile and synbiotic treatment, which have finally formed a set of standardized diagnosis and treatment systems. The present review intends to report the history, current status and remaining bottlenecks of the diagnosis and treatment system of hilar cholangiocarcinoma in Japan as follows.

[Advances in perioperative antiviral therapy for HBV/HCV-associated hepatocellular carcinoma].

Chronic viral hepatitis has a high prevalence rate in China, and the presence or absence of hepatitis virus replication is closely associated with the surgical outcome of patients. Therefore, perioperative antiviral therapy becomes an important method for improving patients' outcome. On the basis of treatment modalities and features of different viral infections, this article elaborates on the strategies and effects of perioperative antiviral therapy, in order to guide clinical practice and improve patients' prognosis.

Perioperative NALIRIFOX in patients with resectable pancreatic ductal adenocarcinoma: The open-label, multicenter, phase II nITRO trial.

BACKGROUND: Upfront surgery followed by postoperative treatment is a commonly adopted treatment for resectable pancreatic ductal adenocarcinoma (rPDAC). However, the risk of positive surgical margins, the poor recovery that often impairs postoperative treatments, and the risk of recurrence might limit the outcome of this strategy. This study evaluated the safety and the activity of liposomal irinotecan 50 mg/m2 + 5-fluorouracil 2400 mg/m2 + leucovorin 400 mg/m2 + oxaliplatin 60 mg/m2 (NALIRIFOX) in the perioperative treatment of patients with rPDAC. METHODS: Eligible patients had a rPDAC with < 180° interface with major veins' wall. Patients received 3 cycles before and 3 cycles after resection with NALIRIFOX, days 1 and 15 of a 28-day cycle. The primary endpoint was the proportion of patients undergoing an R0 resection. RESULTS: 107 patients began preoperative treatment. Nine patients discontinued the treatment because of related or unrelated adverse events. Disease-control rate was 92.9%. 87 patients underwent surgical exploration, 11 had intraoperative evidence of metastatic disease, and 1 died for surgical complications. R0 resection rate was 65.3%. 49 patients completed the three postoperative cycles. The most common grade ≥ 3 adverse events were diarrhea and neutropenia. Median overall survival (OS) of ITT patients was 32.3 months (95% CI 27.8-44.3). Median disease-free and OS from surgery of resected patients were 19.3 (95% CI 12.6-34.1) and 40.3 months (95% CI 29-NA), respectively. CONCLUSION: Perioperative NALIRIFOX was manageable and active, and deserves further investigation in randomized trials comparing it with standard upfront surgery followed by adjuvant therapy.

Case report: Nutritionally supported perioperative chemo-immunotherapy for advanced gastric cancer with incomplete pyloric obstruction.

This case describes the benefits of perioperative chemo-immunotherapy for advanced gastric cancer and incomplete pyloric obstruction, supplemented with nutritional support. Early parenteral nutrition to stabilize nutritional status and mitigate nutrition impact symptoms, and in addition, throughout the chemo-immunotherapy perioperative period also maintained oral nutrition support and a tailored dietary plan. Above nutritional support maintained the patient's physical condition during immunotherapy. Eventually, this combination therapy plan leads to a partial response. On the other hand, a combination of therapies that focus more on immune checkpoint inhibitor may be able to mitigate the side effects of chemotherapy. Such findings may yield novel prospects for patients with advanced gastric cancer and incomplete pyloric obstruction, enabling them to achieve better outcomes.

Pathological Response and Outcomes in Patients With Metastatic Renal Cell Carcinoma (mRCC) Receiving Immunotherapy-Based Therapies and Undergoing Deferred Cytoreductive Nephrectomy (CN).

In this study we evaluated outcomes of patients with metastatic renal cell carcinoma who received immunotherapy before surgery. We found that receiving immunotherapy combinations before surgery can offer patients benefits in reducing tumor size and improving disease control. BACKGROUND: Immunotherapy (IO) has improved outcomes for patients with metastatic renal cell carcinoma (mRCC). However, the timing of surgical intervention for cytoreductive nephrectomy (CN) is still controversial for this group of patients. PATIENTS AND METHODS: We identified patients with mRCC receiving IO-based therapies and undergoing CN. Patients were divided into 2 cohorts: those who underwent upfront CN and those who underwent deferred CN. Pathologic and radiographic features along with clinical outcomes were systematically collected. Comparisons were performed using Chi-square test, paired t-Test or Mann-Whitney-U test. Progression Free survival (PFS) and Overall Survival (OS) were estimated using the Kaplan-Meier method. RESULTS: Fifty-one patients with mRCC were included, with a median follow-up of 21 months. 38 (74.5%) patients received IO-based therapies prior to CN, while 13 (25.5%) patients underwent up-front CN. IO-based therapies reduced median tumor size from pretreatment 10 cm to 8.6 cm post-treatment when given prior to CN. IO-TKI had a trend toward higher tumor shrinkage (-2.3 vs -1.2 cm). Pathologic T downstaging occurred in 42% (n=16) of patients, 11% (n=4) of whom had pT0 disease. Thrombus downstaging occurred in 13% (n=6) of patients, all with either partial response (PR) or complete response (CR) in metastases. PFS (HR=0.7, 95% CI 0.29-1.98, p=0.58) and OS (HR 0.4, 95% CI 0.13-1.57, p=0.21) were not statistically significant between 2 cohorts. CONCLUSIONS: IO-based therapies, particularly IO-TKIs, resulted in pathologic necrosis and reductions in tumor size prior to deferred CN. PFS and OS were similar for patients who received either upfront IO-based therapy or after CN.

Efficacy and safety of perioperative melatonin for postoperative delirium in patients undergoing surgery: a systematic review and meta-analysis.

OBJECTIVE: To assess the efficacy and safety of perioperative melatonin and melatonin agonists in preventing postoperative delirium (POD). METHODS: We conducted a systematic search for randomized controlled trials (RCTs) published through December 2022. The primary outcome was efficacy based on the incidence of POD (POD-I). Secondary outcomes included efficacy and safety according to the length of hospital or intensive care unit stay, in-hospital mortality, and adverse events. Subgroup analyses of POD-I were based on the type and dose of drug (low- and high-dose melatonin, ramelteon), the postoperative period (early or late), and the type of surgery. RESULTS: In the analysis (16 RCTs, 1981 patients), POD-I was lower in the treatment group than in the control group (risk ratio [RR] = 0.57). POD-I was lower in the high-dose melatonin group than in the control group (RR = 0.41), whereas no benefit was observed in the low-dose melatonin and ramelteon groups. POD-I was lower in the melatonin group in the early postoperative period (RR = 0.35) and in patients undergoing cardiopulmonary surgery (RR = 0.54). CONCLUSION: Perioperative melatonin or melatonin agonist treatment suppressed POD without severe adverse events, particularly at higher doses, during the early postoperative period, and after cardiopulmonary surgery.

Impact of immediate breast reconstruction on perioperative therapy: insights from a Japanese Nationwide Registry.

BACKGROUND: Immediate breast reconstruction (IBR) is a common oncoplastic procedure used in breast cancer surgery. This study aims to investigate compliance with prosthetic breast reconstruction guidelines and its impact on perioperative treatment. METHODS: We reviewed data from the National Clinical Database-Breast Cancer Registry between January 2019 and December 2020. We compared perioperative treatment implementation between the IBR and non-IBR groups by subtype matching for age, menopausal status, T stage, N stage, and histology. RESULTS: A total of 8,860 patients with breast cancer who underwent IBR (6,075 breast prostheses, 2,492 autologous tissues, and 293 others) were identified. The compliance rate with the guidelines for prosthetic breast reconstruction was 97.7%. After matching, chemotherapy for luminal A-like diseases was significantly less frequent in the IBR group than in the non-IBR group (16.3% vs 20.5%, p < 0.001), and radiotherapy was less frequent in luminal A-like and HER2-positive patients (7.2% vs 9.0%, p = 0.010 and 7.1% vs 11.4%, p = 0.005, respectively). Among the 1-3 node-positive cases, fewer patients with prosthetic IBR received radiotherapy than those without IBR (15.7% vs 26.4%, p < 0.001). CONCLUSION: Prosthetic breast reconstruction was performed with strict adherence to the Japanese guidelines. The implementation rates of chemotherapy and radiotherapy were lower in the specific IBR group than those in the non-IBR group. Therefore, large-scale, long-term follow-up data are required.

Efficacy and safety of perioperative therapy for locally resectable gastric cancer: A network meta-analysis of randomized clinical trials.

BACKGROUND: Gastric cancer (GC) is the fifth most commonly diagnosed malignancy worldwide, with over 1 million new cases per year, and the third leading cause of cancer-related death. AIM: To determine the optimal perioperative treatment regimen for patients with locally resectable GC. METHODS: A comprehensive literature search was conducted, focusing on phase II/III randomized controlled trials (RCTs) assessing perioperative chemotherapy and chemoradiotherapy in treating locally resectable GC. The R0 resection rate, overall survival (OS), disease-free survival (DFS), and incidence of grade 3 or higher nonsurgical severe adverse events (SAEs) associated with various perioperative regimens were analyzed. A Bayesian network meta-analysis was performed to compare treatment regimens and rank their efficacy. RESULTS: Thirty RCTs involving 8346 patients were included in this study. Neoadjuvant XELOX plus neoadjuvant radiotherapy and neoadjuvant CF were found to significantly improve the R0 resection rate compared with surgery alone, and the former had the highest probability of being the most effective option in this context. Neoadjuvant plus adjuvant FLOT was associated with the highest probability of being the best regimen for improving OS. Owing to limited data, no definitive ranking could be determined for DFS. Considering nonsurgical SAEs, FLO has emerged as the safest treatment regimen. CONCLUSION: This study provides valuable insights for clinicians when selecting perioperative treatment regimens for patients with locally resectable GC. Further studies are required to validate these findings.

Perioperative immune checkpoint blockades improve prognosis of resectable non-small cell lung cancer.

OBJECTIVES: Immune checkpoint blockades (ICB) have been proven to improve prognosis of non-small cell lung cancer in the neoadjuvant setting, while whether its perioperative use could bring extra benefit remained unidentified. We aimed to demonstrate the prognostic benefit of perioperative ICB over preoperative-only use and investigate who could benefit from this 'sandwich ICB therapy'. METHODS: Patients undergoing neoadjuvant therapy followed by surgery from 2018 to 2022 were retrospectively reviewed, and were divided into 4 groups based on the perioperative regimens: pre-ICB + post-computed tomography (CT), pre-ICB-only, pre-CT + post-ICB and pre-CT-only. Treatment-related adverse events, surgical outcomes, therapeutic response, recurrence-free survival and overall survival were compared. RESULTS: Of 214 enrolled patients with preoperative therapy, 108 underwent immunochemotherapy and 106 underwent platinum-based chemotherapy. Compared with preoperative chemotherapy, preoperative immunochemotherapy was demonstrated with significantly higher major pathologic response (57/108 vs 12/106) and pathologic complete response (35/108 vs 4/106) rates with comparable adverse events. Regarding survival, perioperative ICB significantly improved the recurrence-free survival [versus pre-CT-only hazard ratio (HR) 0.15; 95% CI 0.09-0.27; versus pre-ICB-only HR 0.36; 95% CI 0.15-0.88] and overall survival (versus pre-CT-only HR 0.24; 95% CI 0.08-0.68). In patients without major pathologic response, perioperative ICB was observed to decrease the risk of recurrence (HR 0.31; 95% CI 0.11-0.83) compared with preoperative ICB, and was an independent prognostic factor (P < 0.05) for recurrence-free survival. CONCLUSIONS: Perioperative ICB showed promising efficacy in improving pathological response and survival outcomes of resectable non-small cell lung cancer. For patients without major pathologic response after resection followed by preoperative ICB, sequential ICB treatment could be considered.