Postoperative Adverse Events Following Neoadjuvant Therapy and Surgery for Borderline Resectable Pancreatic Cancer in a Phase 2 Clinical Trial (Alliance A021501).

BACKGROUND: Postoperative adverse events (AEs) in patients with borderline resectable pancreatic ductal adenocarcinoma (BR-PC) treated with neoadjuvant therapy and pancreatectomy in the national cooperative group setting have not been previously characterized. We conducted a preplanned secondary analysis of patients enrolled on the Alliance A021501 clinical trial to quantify perioperative AE rates. METHODS: The A021501 phase 2 trial randomized patients with BR-PC to receive 8 doses of mFOLFIRINOX (Arm 1) or 7 doses of mFOLFIRINOX and hypofractionated radiotherapy (Arm 2), followed by pancreatectomy (December 31, 2016 to May 31, 2019). Adverse events were assessed 90 days after pancreatectomy. RESULTS: Of 126 enrolled patients, 51 (40%) underwent pancreatectomy (n = 32, Arm 1; n = 19, Arm 2) at 28 institutions. Five (10%) patients required reoperation within 90 days; 56% of patients (n = 27/48) experienced at least one grade 3 or higher AE (50% vs. 67%, p = 0.37). Ninety-day mortality was 2.0%. Readmission was less frequent in Arm 1 (16% vs. 42%, p = 0.05), but there were no differences between study arms in rates of reoperation (13% vs. 5%), pancreatic fistula or intra-abdominal abscess requiring drainage (9% vs. 16%), or wound infection (6% vs. 16%). Pancreatic fistula or intra-abdominal abscess requiring drainage was associated with receipt of adjuvant therapy (p = 0.012). No difference in overall survival was observed based on occurrence of postoperative AEs (hazard ratio = 1.1; 95% confidence interval 0.5-2.6). CONCLUSIONS: In this multicenter study, rates of postoperative AEs were consistent with those previously reported. Multimodality trials of preoperative therapy for BR-PC may be performed in the cooperative group setting with careful quality assurance and safety monitoring. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02839343.

1657 Resected Gastric Adenocarcinomas at a Single Institution: Outcomes and Trends over 17 Years.

BACKGROUND: Outside of clinical trials, real-world data of advanced gastric cancers (AGCs) managed with perioperative or adjuvant chemotherapy with a backbone of D2 lymphadenectomy is limited. PATIENTS AND METHODS: Curative resections for gastric adenocarcinoma between January 2003 and January 2020 at the Tata Memorial Centre were analyzed, comparing three time periods marking major increments in annual gastric resections (GRs). RESULTS: 1657 radical gastric resections were performed with a morbidity and mortality rate of 34.9% and 1.4%, respectively. Over three consecutive periods, the number of annual GRs increased from 56/year to 97/year to 156/year (P < 0.001) with a significant escalation in surgical magnitude and complexity. Improvement in surgical quality indicators (median lymph node yield from 15 to 25, P < 0.001 and margin negativity from 8.2 to 5.5%, P = 0.002) was observed with no corresponding increase in severe complications (6.9%) or mortality (1.4%). The proportion of distal and signet ring cancers was found to decrease over time, with an increase in proximal cancers and younger age at presentation. Overall, 90% of GRs were for AGCs with a median overall survival (OS) of 4.4 years (± 6 months), and 5-year OS rate of 47.6% (± 1.9%). CONCLUSIONS: Change in pattern of tumor characteristics was observed. Aggressive treatment options for AGC were employed progressively with excellent survival. With increase in volumes, improvements in surgical quality indicators, and a relative improvement in postoperative mortality was observed. These results provide a roadmap for developing dedicated gastric cancer centers.

Efficacy of Mirogabalin for Taxane-associated Chemotherapy-induced Peripheral Neuropathy in Perioperative Chemotherapy for Early Breast Cancer.

BACKGROUND/AIM: Treatment with taxanes can result in chemotherapy-induced peripheral neuropathy (CIPN). We investigated the efficacy and safety of mirogabalin for the treatment of CIPN in patients who had been administered perioperative chemotherapy including taxane-based agents for breast cancer. PATIENTS AND METHODS: We retrospectively analyzed the case of 43 patients with early breast cancer who received a taxane as perioperative chemotherapy and were administered mirogabalin at the diagnosis of CIPN. RESULTS: Thirty-six patients (83.7%) had grade 1 CIPN and the other seven patients (16.3%) had grade 2 CIPN. The median mirogabalin dose was 10 mg (5-30 mg). CIPN improved from grade 1 to 0 in 12 patients (27.9%) and from grade 2 to 1 in one patient (2.3%); 13 (30.2%) patients thus had an objective therapeutic response. There were no cases in which chemotherapy was reduced or discontinued due to CIPN. Adverse events were evaluated by Common Terminology Criteria for Adverse Events and included five cases of dizziness (11.7%), three of somnolence (7.0%), and two of nausea (4.7%), all of which were grade ≤2. There were no cases of serious (grade ≥3) adverse effects. CONCLUSION: Mirogabalin may be effective and safe for treating CIPN of patients who receive a taxane in a perioperative breast cancer setting.

Effect of histological subtype on the efficacy of perioperative chemotherapy in pulmonary sarcomatoid carcinoma: a retrospective study based on SEER population.

Background: The efficacy of perioperative chemotherapy (PC) in pulmonary sarcomatoid carcinoma (PSC) is controversial. We conducted this study to investigate the effect of different histological subtypes on the efficacy of PC in PSC patients. Methods: Clinicopathological data of 811 PSC patients of different histological subtypes were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier method and log-rank test were used to evaluate the effects of PC on the overall survival (OS) and cancer-specific survival (CSS) in different subtypes of PSC patients. Propensity score matching (PSM) was used to reduce potential confounding effects. Subgroup analyses were conducted to further investigate the efficacy of PC in patients with different characteristics. Results: A total of 210 (25.89%) enrolled PSC patients received PC. PC was not associated with OS or CSS benefit in pleomorphic carcinoma, giant cell carcinoma, or spindle cell carcinoma patients, neither before nor after matching. But survival benefit of PC was observed in carcinosarcoma patients both before (5-year OS: 48.79% vs. 38.75%, P=0.01) and after (5-year OS: 51.29% vs. 17.54%, P=0.003) matching. Subgroup analyses showed that in patients whose tumor larger than 4 cm, PC was still associated with improved survival in carcinosarcoma, but not in the other histological subtypes of PSC. Conclusions: The efficacy of PC varies between different subtypes of PSC. Survival benefit of PC was only observed in carcinosarcoma patients, but not in pleomorphic carcinoma, giant cell carcinoma, or spindle cell carcinoma patients. Histological subtype should be considered when treating PSC patients with PC.

Re-consideration of Lymph Node Metastasis in Pancreatic Cancer Patients Following Radical Resection: A Retrospective Study.

BACKGROUND/AIM: Perioperative chemotherapy has become more common in patients with pancreatic cancer (PC), and the significance of lymph node (LN) metastasis and the role of surgical resection in PC have gradually evolved. In the present study, we reconsidered the significance of LN metastasis for patients with PC. PATIENTS AND METHODS: We analyzed 142 PC patients who underwent radical resection at our hospital between September 2012 and December 2021. Patients were divided into three groups based on the performance of preoperative chemotherapy, as follows: up-front surgery (US, n=109), neoadjuvant chemotherapy (NAC, n=22), and conversion surgery (CS, n=11). The characteristics of patients with LN metastasis in the US group were clarified, and a prognostic analysis was performed. The prognostic impact of LN metastasis in the NAC/CS group was examined and compared to that in the US group. RESULTS: Multivariate analysis revealed that high CA19-9 levels, large tumor size, and positive lymphatic invasion were significantly associated with LN metastasis. LN metastasis and portal vein invasion were independent poor prognostic factors in multivariate analysis. Patients without LN metastasis in the NAC group tended to have a better prognosis than those in the US group; however, the prognosis of patients with LN metastasis was similar between the two groups. In the CS and US groups, the prognosis was comparable for patients with and without LN metastasis. CONCLUSION: LN metastasis is a notably poor prognostic factor for PC patients, even after NAC, and more aggressive perioperative treatments may be considered for these patients.

Perioperative Chemotherapy Including Bevacizumab in Potentially Curable Metastatic Colorectal Cancer: Long-Term Follow-Up of the ASSO-LM1 Trial.

In 2007, the ASSO-LM1 trial, a multicenter prospective study, was initiated to investigate the resectability (R0) rate following preoperative combination therapy with XELOX and bevacizumab in patients with potentially resectable colorectal liver metastases. Six cycles of systemic therapy were administered preoperatively, although the sixth cycle did not include bevacizumab, resulting in 5 weeks between the last bevacizumab dose and surgery. Treatment with bevacizumab plus XELOX was restarted for another six cycles postoperatively. In total, 43 patients were enrolled in the ASSO-LM1 trial. Eight patients were ineligible for resection due to protocol violation and progression in two patients. The resectability of operated patients was 97% with 34 R0 resections and one R1 resection. Postoperative morbidity occurred in 22% of patients, of which three operative revisions were related to the primary tumor resection. Efficacy results for response in 38 eligible patients confirmed an ORR of 66%, 31% SD and 3% PD according to RECIST. Preoperative grade 3/4 adverse events were 17% diarrhea, 5% HFS and 5% thromboembolic events. Overall survival significantly differed depending upon the fulfillment of adjuvant treatment in curative resected patients (59.1 mo vs. 30.8 mo). In conclusion, the ASSO-LM1 trial is a hypothesis-generating study confirming the prognostic benefits of perioperative therapy with XELOX and bevacizumab in patients with metastatic colorectal cancer confined to the liver.

Perioperative or neoadjuvant chemotherapy for locally advanced gastric or gastroesophageal junction cancer: from independent evidence in the West, the East, and Japan to global collaboration.

The survival outcome of patients with locally advanced gastric or gastroesophageal junction (G/GEJ) cancer remains unsatisfactory, and improvements in survival and recurrence remain urgent issues for clinicians worldwide. Prior to the 2000s, locally advanced G/GEJ was a different disease between the West and the East regarding diagnosis, surgery, and prognosis. However, recent advances in medical oncology have set the stage for harmonization. Herein, this review highlights clinical trials of perioperative or neoadjuvant chemotherapy conducted during the past two decades to provide insights into future directions. We focused on pivotal clinical trials of perioperative or neoadjuvant chemotherapy for patients with locally advanced G/GEJ cancer. We paid special attention to the indication and oncological outcomes of perioperative or neoadjuvant chemotherapy. The attempts to investigate the optimal treatment strategy for locally advanced G/GEJ cancer over the past 20 years have resulted in a global consensus on the necessity of perioperative or neoadjuvant chemotherapy, although there have been different circumstances regarding treatment for G/GEJ cancer among the West, the East other than Japan, and Japan. Two randomized global phase III trials, the KEYNOTE-585 and MATTHERHORN, were successfully accomplished for a common indication. Furthermore, perioperative immunotherapy suggested a new indication with molecular biomarkers such as microsatellite status or PD-L1 status beyond the conventional tumor-lymph node-metastasis (TNM) staging system. Global studies provide the stage for discussing the future optimal indication of neoadjuvant chemotherapy, opening the door for future global collaborations to better treat patients with locally advanced G/GEJ cancer.

Perioperative chemotherapy with docetaxel plus oxaliplatin and S-1 (DOS) versus oxaliplatin plus S-1 (SOX) for the treatment of locally advanced gastric or gastro-esophageal junction adenocarcinoma (MATCH): an open-label, randomized, phase 2 clinical trial.

BACKGROUND: It remains unclear whether addition of docetaxel to the combination of a platinum and fluoropyrimidine could provide more clinical benefits than doublet chemotherapies in the perioperative treatment for locally advanced gastric/gastro-esophageal junction (LAG/GEJ) cancer in Asia. In this randomized, phase 2 study, we assessed the efficacy and safety of perioperative docetaxel plus oxaliplatin and S-1 (DOS) versus oxaliplatin plus S-1 (SOX) in LAG/GEJ adenocarcinoma patients. METHODS: Patients with cT3-4 Nany M0 G/GEJ adenocarcinoma were randomized (1:1) to receive 4 cycles of preoperative DOS or SOX followed by D2 gastrectomy and another 4 cycles of postoperative chemotherapy. The primary endpoint was major pathological response (MPR). RESULTS: From Aug, 2015 to Dec, 2019,154 patients were enrolled and 147 patients included in final analysis, with a median age of 60 (26-73) years. DOS resulted in significantly higher MPR (25.4 vs. 11.8%, P = 0.04). R0 resection rate, the 3-year PFS and 3-year OS rates were 78.9 vs. 61.8% (P = 0.02), 52.3 vs. 35% (HR 0.667, 95% CI: 0.432-1.029, Log rank P = 0.07) and 57.5 vs. 49.2% (HR 0.685, 95% CI: 0.429-1.095, Log rank P = 0.11) in the DOS and SOX groups, respectively. Patients who acquired MPR experienced significantly better survival. DOS had similar tolerance to SOX. CONCLUSIONS: Perioperative DOS improved MPR significantly and tended to produce longer PFS compared to SOX in LAG/GEJ cancer in Asia, and might be considered as a preferred option for perioperative chemotherapy and worth further investigation.

Oligometastasis of Gastric Cancer: A Review.

The concept of oligometastasis is not yet fully established in the field of gastric cancer. However, metastatic lesions that are localized, technically resectable at diagnosis, present a certain response to preoperative chemotherapy, and present favorable survival outcomes with local treatments, sometimes in combination with chemotherapy, are recognized as oligometastasis in the field of gastric cancer. Oligometastasis is noted in European Society for Medical Oncology guidelines and Japanese gastric cancer treatment guidelines, and local treatment is mentioned as one of the pivotal treatment options for oligometastasis. Solitary liver metastasis or a small number of liver metastases; retroperitoneal lymph node metastasis, especially localized para-aortic lymph node metastasis; localized peritoneal dissemination; and Krukenberg tumor are representative types of oligometastasis in gastric cancer. The AIO-FLOT3 trial prospectively evaluated the efficacy of multimodal treatments for gastric cancer with oligometastasis, including surgical resection of primary and metastatic lesions combined with chemotherapy, confirming favorable survival outcomes. Two phase 3 studies are ongoing to investigate the efficacy of surgical resection combined with perioperative chemotherapy compared with palliative chemotherapy. Thus far, the evidence suggests that multimodal treatment for oligometastasis of gastric cancer is promising.

Prognostic factors and treatment outcomes in patients with pleomorphic rhabdomyosarcoma: a population-based cohort study.

BACKGROUND: Pleomorphic rhabdomyosarcoma is a rare sarcoma in adults. The clinical characteristics, outcomes and prognostic factors associated with pleomorphic rhabdomyosarcoma remain unclear. METHODS: We retrospectively analyzed data from the Bone and Soft Tissue Tumor Registry of Japan, and enrolled patients with pleomorphic rhabdomyosarcoma. Disease-specific overall survival, local recurrence-free survival and distant metastasis-free survival were estimated using the Kaplan-Meier method; Cox regression model was used to identify prognostic factors. RESULTS: In total, 182 patients with pleomorphic rhabdomyosarcoma were included. Median age was 63 (range 20-95) years. The lower extremity (48%) was the most frequent tumor origin site, while head and neck were rare (4%). A total of 43 patients (24%) had distant or regional nodal metastases at first presentation. In all cases, the 2-year and 5-year survival rates were 66.3% and 54.1%, respectively. Distant metastasis was a significant poor prognostic factor (Hazard ratio 6.65; 95% confidence intervals, 3.00-14.75, P < 0.0001), with median survival of such patients being 9.4 (95% confidence intervals: 5.3-12.2) months. In 134 localized cases, the 2-year and 5-year survival rates were 91.5% and 68.3%, respectively. Large tumor size and older age were associated with poorer prognosis. Through data from localized and locally curative cases extracted and adjusted by propensity score matching, we found that perioperative chemotherapy did not improve disease-specific overall survival, distant metastasis-free survival or local recurrence-free survival. CONCLUSIONS: Clinical characteristics and outcomes of pleomorphic rhabdomyosarcoma are similar to those of other high-grade soft tissue sarcomas. Pleomorphic rhabdomyosarcoma may be less chemosensitive, and a strategy other than the standard cytotoxic chemotherapy is required to improve its prognosis.

Short-term outcomes of preoperative chemotherapy with docetaxel, oxaliplatin, and S-1 for gastric cancer with extensive lymph node metastasis (JCOG1704).

BACKGROUND: The prognosis for marginally resectable gastric cancer with extensive lymph node metastasis (ELM) remains unfavorable, even after R0 resection. To assess the safety and efficacy of preoperative docetaxel, oxaliplatin, and S-1 (DOS), we conducted a multicenter phase II trial. METHODS: Eligibility criteria included histologically proven HER2-negative gastric adenocarcinoma with bulky nodal (bulky N) involvement around major branched arteries or para-aortic node (PAN) metastases. Patients received three cycles of docetaxel (40 mg/m2, day 1), oxaliplatin (100 mg/m2, day 1), and S-1 (80-120 mg/body, days 1-14), followed by gastrectomy with D2 plus PAN dissection. Subsequently, patients underwent postoperative chemotherapy with S-1 for 1 year. The primary endpoint was major (grade ≥ 2a) pathological response rate (pRR) according to the Japanese Classification of Gastric Carcinoma criteria. RESULTS: Between October 2018 and March 2022, 47 patients (bulky N, 20; PAN, 17; both, 10) were enrolled in the trial. One patient was ineligible. Another declined any protocol treatments before initiation. Among the 45 eligible patients who initiated DOS chemotherapy, 44 (98%) completed 3 cycles and 42 (93%) underwent R0 resection. Major pRR and pathological complete response rates among the 46 eligible patients, including the patient who declined treatment, were 57% (26/46) and 24% (11/46), respectively. Common grade 3 or 4 toxicities were neutropenia (24%), anorexia (16%), febrile neutropenia (9%), and diarrhea (9%). No treatment-related deaths occurred. CONCLUSIONS: Preoperative chemotherapy with DOS yielded favorable pathological responses with an acceptable toxicity profile. This multimodal approach is highly promising for treating gastric cancer with ELM.

Updated German guideline on diagnosis and treatment of squamous cell carcinoma and adenocarcinoma of the esophagus.

Diagnosis and therapy of esophageal carcinoma is challenging and requires a multidisciplinary approach. The purpose of the updated German guideline "Diagnosis and Treatment of Squamous Cell Carcinoma and Adenocarcinoma of the Esophagus-version 3.1" is to provide practical and evidence-based advice for the management of patients with esophageal cancer. Recommendations were developed by a multidisciplinary expert panel based on an extensive and systematic evaluation of the published medical literature and the application of well-established methodologies (e.g. Oxford evidence grading scheme, grading of recommendations). Accurate diagnostic evaluation of the primary tumor as well as lymph node and distant metastases is required in order to guide patients to a stage-appropriate therapy after the initial diagnosis of esophageal cancer. In high-grade intraepithelial neoplasia or mucosal carcinoma endoscopic resection shall be performed. Whether endoscopic resection is the definitive therapeutic measure depends on the histopathological evaluation of the resection specimen. Esophagectomy should be performed minimally invasive or in combination with open procedures (hybrid technique). Because the prognosis in locally advanced esophageal carcinoma is poor with surgery alone, multimodality therapy is recommended. In locally advanced adenocarcinomas of the esophagus or esophagogastric junction, perioperative chemotherapy or preoperative radiochemotherapy should be administered. In locally advanced squamous cell carcinomas of the esophagus, preoperative radiochemotherapy followed by complete resection or definitive radiochemotherapy without surgery should be performed. In the case of residual tumor in the resection specimen after neoadjuvant radiochemotherapy and R0 resection of squamous cell carcinoma or adenocarcinoma, adjuvant immunotherapy with nivolumab should be given. Systemic palliative treatment options (chemotherapy, chemotherapy plus immunotherapy, immunotherapy alone) in unresectable or metastastic esophageal cancer depend on histology and are stratified according to PD-L1 and/or Her2 expression.

The Role of Lymph Node Dissection in Patients With Muscle-Invasive Bladder Cancer Who Underwent Radical Cystectomy Following Neoadjuvant Chemotherapy.

BACKGROUND: The interaction between lymph node dissection (LND) during radical cystectomy (RC) and neoadjuvant chemotherapy (NAC) remains unclear. This study aimed to evaluate the role of LND in patients undergoing RC after NAC. PATIENTS AND METHODS: We retrospectively analyzed 259 patients with muscle-invasive bladder cancer (MIBC) who underwent RC following NAC at Fujita Health University Hospital and Fujita Health University Okazaki Medical Center between 2010 and 2022. Baseline characteristics, pathological outcomes, recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were compared between propensity score (PS)-matched cohorts. RESULTS: PS matching analysis resulted in 94 matched pairs from the adequate (standard or extended template) and inadequate (limited template or unilateral- or no-LND) LND groups. The median number of dissected nodes was significantly higher in the adequate LND group than in the inadequate LND group (19 vs. 5, P < .001). Similarly, a higher pathological node-positive rate (ypN+) was observed in the adequate group than in the inadequate group (18.1% vs. 7.4%, P = .03). The adequate LND group identified more ypN+ with ≤ ypT1 cases than the inadequate group (4 vs. 1). There were no statistically significant differences between the adequate and inadequate groups in RFS (P = .94), CSS (P = .54), and OS (P = .65). Subgroup analysis also showed comparable survival rates, even in patients with ≥ pT3 or cN+ disease. ypN+ was an independent predictor of OS in the Cox regression analysis, while adequate LND and the number of lymph nodes removed (≥10 or ≥15) were not associated with survival. CONCLUSIONS: Although adequate LND did not show a significant therapeutic effect in RC after NAC, adequate LND may have an important diagnostic role in detecting ypN+, which is a robust predictor, and is a useful biomarker to perform appropriate adjuvant immunotherapy especially in ≤ ypT1 cases.

Addition of trastuzumab to perioperative chemotherapy in HER2-positive gastroesophageal adenocarcinoma patients: A multicenter retrospective observational AGEO study.

BACKGROUND: Approximately 10-20% of patients with gastroesophageal adenocarcinoma (GE-ADK) have HER2-positive tumors. The addition of trastuzumab to chemotherapy improves OS in patients with advanced disease. We investigated the effect of perioperative trastuzumab on survival outcomes. METHODS: This French, multicenter, retrospective observational study included HER2-positive GE-ADK patients treated between January 2015 and December 2020. The primary endpoint was DFS at 18 months. Secondary endpoints were pathological complete response rate (pCR), R0 resection rate, OS, and toxicity. RESULTS: Forty-eight patients were included, and they received a median of 6 cycles of preoperative treatment, with grade III/IV adverse events occurring in 23%. Pathologic complete response (pCR) and major pCR according to Mandard system were achieved in 5/48 (10%) and 20/48 (42%) patients, respectively. Loss of HER2 expression was observed in 18/48 (38%) patients. Postoperative complications rate according to the Clavien Dindo classification (≥3) was 37.5%. After a median follow-up of 29 months, the 18-month DFS was 80.4% (95% CI 68.9-93.8) and the 2-year OS rate was 89.0%. Subgroup analysis showed a longer DFS for gastric tumor than gastro-esophageal junction tumor. CONCLUSIONS: This study suggests that perioperative chemotherapy with trastuzumab in patients with HER2-positive GE-ADK is feasible and safe with encouraging survival.

DNA mismatch repair deficiency and outcomes of patients with locally advanced gastric cancer treated with preoperative docetaxel, oxaliplatin, and S-1 plus surgery and postoperative S-1 or surgery plus postoperative S-1: a sub-analysis of the phase 3 PRODIGY trial.

BACKGROUND: The benefit of adjuvant chemotherapy for locally advanced gastric cancer (LAGC) patients with DNA mismatch repair (MMR) deficiency (D-MMR) is controversial due to concerns about its potential detrimental effect. The PRODIGY trial showed the survival benefit of adding preoperative docetaxel, oxaliplatin, and S-1 (DOS) to surgery plus postoperative S-1 for LAGC patients. In this sub-analysis, we evaluated the benefit of preoperative DOS according to MMR status. METHODS: Among patients enrolled in the PRODIGY trial treated with either preoperative DOS followed by surgery and postoperative S-1 (CSC arm), or surgery and postoperative S-1 (SC arm) at Asan Medical Center (n = 249), those in the full analysis set with available tissue to assess MMR status were included in the present analysis. RESULTS: A total of 231 patients (CSC arm, n = 108; SC arm, n = 123) were included (median age, 58 years [range, 27-75]), and 21 patients (CSC arm, n = 8 [7.4%]; SC arm, n = 13 [10.6%]) had D-MMR tumors. Progression-free survival and overall survival tended to be superior in the CSC arm than in the SC arm among D-MMR patients (HR 0.48 [95% CI 0.09-2.50]; log-rank P = 0.37 and HR 0.55 [95% CI 0.11-2.86]; log-rank P = 0.46, respectively), as well as among proficient MMR (P-MMR) patients (HR 0.68 [95% CI 0.46-1.03]; log-rank P = 0.07 and HR 0.75 [95% CI 0.49-1.14]; log-rank P = 0.17, respectively). CONCLUSION: Preoperative DOS followed by surgery and postoperative S-1 may be considered a treatment option for LAGC patients regardless of MMR status.

Comparative Study on the Efficacy of Two Perioperative Chemotherapy Regimens for Lumbar Brucellosis.

Objective: The clinical efficacy of perioperative chemotherapy regimen (rifampicin, doxycycline, levofloxacin, ceftriaxone) was evaluated for lumbar brucellosis spondylitis patients with neurological injury. Methods: In Beijing Ditan Hospital affiliated with Capital Medical University, 32 patients with lumbar brucellosis spondylitis underwent surgery and triple perioperative chemotherapy (rifampicin, doxycycline, levofloxacin) between 2011 and 2021 due to neurological injury, and 34 patients matched up with the triple group underwent rifampicin, doxycycline, levofloxacin, and ceftriaxone. Both groups were compared in terms of changes in inflammation index, low back/leg pain, lumbar function, neurological function, and adverse drug reactions. Results: There was no significant difference in erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), low back pain visual analogue scale (VAS), leg pain VAS, lumbar Oswestry disability index (ODI) and nerve function injury rate between the two groups before chemotherapy (P>0.05). The ESR, CRP at 1 week and 2 weeks after chemotherapy and 1 week, 2 weeks, 1 month postoperatively in the quadruple group were significantly lower than those in the triple group, which is the same to ESR 3 months postoperatively (P<0.05). The low back pain VAS, leg pain VAS and lumbar ODI in the quadruple group were significantly lower than those in the triple group at 1 month and 3 months postoperatively (P<0.05). The recovery rate of neurological function in the quadruple group was significantly higher than that in the triple group at 3 and 6 months postoperatively (P<0.05). Both groups did not experience significantly different perioperative and postoperative adverse reactions (P>0.05). Conclusion: For lumbar brucellosis spondylitis with neurological injury, quadruple perioperative chemotherapy of rifampicin, doxycycline, levofloxacin and ceftriaxone can significantly reduce perioperative inflammation, and improve low back/leg pain, as well as promoting neurological function recovery in the short term.

Neoadjuvant chemotherapy for locally advanced gastric cancer in Japan: Consensus meeting at the 77th general meeting of the Japanese Society of Gastroenterological Surgery.

Treatment strategy for locally advanced gastric cancer differs worldwide. Neoadjuvant chemotherapy (NAC) is considered one of the promising treatment options for locally advanced gastric cancer, even in Japan, and clinical trials have been conducted or are ongoing. A consensus meeting was organized at the 77th general meeting of the Japanese Society of Gastroenterological Surgery in 2022, in which the current status and future prospects of NAC for locally advanced gastric cancer were discussed. Participants at the meeting looked forward to the results of the JCOG1509 trial, providing solid evidence regarding NAC. The optimal indications and regimens for NAC were also debated. Patients with cStage III gastric cancer are the main targets of NAC in Japan, and a doublet regimen of S-1 and oxaliplatin was preferred by the participants. However, the feasibility of a triplet regimen with S-1, oxaliplatin, and docetaxel, and that with 5-FU, leucovorin, oxaliplatin, and docetaxel has been demonstrated, and these could become treatment options in Japan. Other points of discussion include perioperative chemotherapy to avoid peritoneal recurrence and for patients with dMMR/MSI-high tumors. The panel regarded NAC as a promising treatment option, and NAC will become the standard treatment for cStage III gastric cancer in Japan if an ongoing clinical trial successfully demonstrates its efficacy.

Clinicopathological features and survival outcomes for gastric adenocarcinoma: Real-world single-center data.

INTRODUCTION: Gastric cancer is the fifth most-common cancer and fourth common cause for cancer-related deaths globally. Surgery preceded or followed by chemotherapy or chemoradiotherapy is considered an optimal treatment for locally advanced gastric cancer. This study is a real-world data from a tertiary referral institute in southern India, in its experience with treating gastric adenocarcinoma over a period of four years with a minimum of two-year follow-up. METHODS: This was a retrospective analysis of data of patients with histologically proven gastric adenocarcinoma enrolled in the Department of Medical Oncology from 2015 to 2018. The demographic details, presentation, staging, treatment received and outcomes of patients with gastric adenocarcinoma were collected and analyzed in this study. RESULTS: Total 488 patients with gastric adenocarcinoma were included for the study. The stage-wise distribution of patients revealed early and locally advanced (45%) and metastatic (55%). The peritoneum and liver were the common sites of metastasis. The treatment distribution of these patients included perioperative chemotherapy followed by surgery (25 [5%]), surgery followed by adjuvant chemotherapy (65 [13%]), surgery alone (16 [3%]), perioperative chemotherapy alone (23 [4%]), palliative chemotherapy (274 [56%]) and supportive care (85 [17%]). The median overall survival for curative, palliative and supportive treatment was 23 (18-28), nine (7.6-10.4) and four (2.7-5.3) months, respectively. The two-year overall survival in the intention to treat population in the primary surgery (n = 81) and perioperative chemotherapy groups (n = 66) was 67.4% vs. 29.9% (p < 0.0001), respectively. CONCLUSION: This study highlights the advanced nature of the presentation of gastric cancer patients and the poor rate of treatment completion. The median survival rates in curative patients remain to be dismally poor. The treatment sequence in curable gastric cancer of surgery followed by adjuvant chemotherapy vs. perioperative chemotherapy followed by surgery needs to be explored in our country.

Perioperative chemotherapy versus adjuvant chemotherapy treatment for resectable locally advanced gastric cancer: a retrospective cohort study.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is increasingly used in locally advanced gastric cancer (LAGC), but the clinical safety and efficacy are still controversial. This study aims to compare perioperative chemotherapy (PEC) with adjuvant chemotherapy (AC) for resectable LAGC. METHODS: Patients who underwent D2 gastrectomy for resectable LAGC were retrospectively reviewed, and divided into NSA group (NAC plus surgery and AC) and SA group (surgery followed by AC). The baseline characteristics and perioperative data were compared. Survival analysis was based on Kaplan-Meier method. Multivariate analyses for prognostic factors were based on the Cox regression. RESULTS: A total of 450 patients were eligible for this study. 218 patients received NAC plus surgery and AC, while 232 upfront surgery followed by AC. The baseline characteristics were comparable between the two groups. NSA group showed significant superiority in R0 resection rate (P = 0.014), excised tumor size (P = 0.038), and tumor downstage (all P < 0.001). NAC did not affect postoperative complications or AC-related grade 3/4 adverse events. Patients in NSA group achieved significantly longer OS (P = 0.021) and DFS (P = 0.002). The Cox regression model showed that NAC was independently associated with better OS (HR 0.245, P = 0.039) and DFS (HR 0.591, P = 0.031). CONCLUSIONS: Compared with SA, the administration of NSA was considered safe and feasible for achieving higher R0 resection rate without increasing the postoperative complications or AC-related grade 3/4 adverse events, and NAC was independently associated with better OS and DFS for resectable LAGC.