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.

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.

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.

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.

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.

Perioperative therapy with FLOT4 significantly increases survival in patients with gastroesophageal and gastric cancer in a large real-world cohort.

In 2019, the FLOT4 protocol was established as the new standard for perioperative therapy in patients with locally advanced gastroesophageal and gastric cancer. Whether this protocol is beneficial in a real-world setting remains a question with limited answers to date. In our study, a large cohort of unselected patients treated with FLOT4 was analyzed and compared to protocols based on 5-FU/platinum derivative. This retrospective analysis included patients with locally advanced gastroesophageal and gastric cancer treated with perioperative FLOT or 5-FU/platinum derivative at University Hospital, Bonn between 2010 and 2022 in a curative setting (n = 99). Overall survival, disease-free survival, therapy response and therapy complications were analyzed. Patients treated with FLOT showed a statistically significant longer median overall survival of 57.8 vs 28.9 months (HR: 0.554, 95% CI: 0.317-0.969, P = .036). Moreover, pathological tumor regression (pTR) was significantly higher in the FLOT group compared to the 5-FU/platinum group (P = .001). Subgroup analysis showed a favorable survival benefit for the FLOT vs 5-FU/platinum derivate in patients with AEG and non-signet cell carcinoma. Overall, FLOT was tolerated well but CTCAE ≥3 grade neutropenia and diarrhea occurred more often within the FLOT group. Similar to the prospective phase II/III trials, FLOT4 was the best protocol for patients with locally advanced gastroesophageal and gastric cancer as perioperative therapy in terms of overall survival and pathological response rate compared to 5-FU/platinum derivative protocols. Interestingly, patients with gastroesophageal cancer benefitted more from this therapy. In contrast, patients with signet ring cells appear not to benefit from addition of docetaxel.

Perioperative Chemotherapy Could Not Improve the Prognosis of Gastric Cancer Patients With Mismatch Repair Deficiency: A Multicenter, Real-World Study.

INTRODUCTION: To date, the role of deficient mismatch repair (dMMR) remains to be proven in gastric cancer, and it is difficult to judge its value in clinical application. Our study aimed to investigate how MMR status affected the prognosis in patients with gastrectomy, as well as the efficacy of neoadjuvant chemotherapy and adjuvant chemotherapy in patients with dMMR with gastric cancer. MATERIALS AND METHODS: Patients with gastric cancer with certain pathologic diagnosis of dMMR or proficient MMR (pMMR) using immunohistochemistry from 4 high-volume hospitals in China were included. Propensity score matching was used to match patients with dMMR or pMMR in 1:2 ratios. Overall survival (OS) and progression-free survival (PFS) curves were plotted using the Kaplan-Meier method and compared statistically using the log-rank test. Univariate and multivariate Cox proportional hazards models based on hazard ratios (HRs) and 95% confidence intervals (CIs) were used to determine the risk factors for survival. RESULTS: In total, data from 6176 patients with gastric cancer were ultimately analyzed, and loss of expression of one or more MMR proteins was observed in 293 patients (293/6176, 4.74%). Compared to patients with pMMR, patients with dMMR are more likely to be older (≥66, 45.70% vs. 27.94%, P < .001), distal location (83.51% vs. 64.19%, P < .001), intestinal type (42.21% vs. 34.46%, P < .001), and in the earlier pTNM stage (pTNM I, 32.79% vs. 29.09%, P = .009). Patients with gastric cancer with dMMR showed better OS than those with pMMR before PSM (P = .002); however, this survival advantage was not observed for patients with dMMR after PSM (P = .467). As for perioperative chemotherapy, results of multivariable Cox regression analysis showed that perioperative chemotherapy was not an independent prognostic factor for PFS and OS in patients with dMMR with gastric cancer (HR = 0.558, 95% CI, 0.270-1.152, P = .186 and HR = 0.912, 95% CI, 0.464-1.793, P = .822, respectively). CONCLUSION: In conclusion, perioperative chemotherapy could not prolong the OS and PFS of patients with dMMR with gastric cancer.

Real-world data analysis of perioperative chemotherapy patterns, G-CSF use, and FN status in patients with early breast cancer.

PURPOSE: This study aimed to describe perioperative chemotherapy patterns, granulocyte colony-stimulating factor (G-CSF) use, and febrile neutropenia (FN) status in patients with early breast cancer (EBC) using real-world data in Japan. METHODS: This retrospective observational study used anonymized claims data. The included patients were ≥ 18 years old, were female, and had breast cancer diagnosis and surgery records between January 2010 and April 2020. Measures included perioperative chemotherapy, G-CSF use (daily and primary prophylaxis [PP]), and FN and FN-related hospitalization (FNH), all examined annually. Perioperative chemotherapy was examined separately for human epidermal growth factor receptor 2-positive/negative (HER2±). A multivariate logistic regression was used to explore the factors associated with FNH. RESULTS: Of 32,597 patients, those with HER2 + EBC treated with anthracycline-based regimens followed by taxane + trastuzumab + pertuzumab increased since 2018, and those with HER2 - EBC treated with doxorubicin/epirubicin + cyclophosphamide followed by taxane and dose-dense regimens increased after 2014. The proportion of patients prescribed daily G-CSF declined after 2014, whereas that of pegfilgrastim PP increased. The incidence proportion of FN remained at approximately 24-31% from 2010 to 2020, while that of FNH declined from 14.5 to 4.0%. The odds of FNH were higher in those aged ≥ 65 years and lower with pegfilgrastim PP administration. CONCLUSION: Despite the increasing use of escalated regimens in the last 5-6 years, FNH continuously declined, and the odds of FNH were lower among patients treated with pegfilgrastim PP. These results may suggest the contribution of PP in part to suppressing FNH levels over the last 5-6 years.

Prognostic Impact of Tumor Markers (CEA and CA19-9) on Patients with Resectable Colorectal Liver Metastases Stratified by Tumor Number and Size: Potentially Valuable Biologic Markers for Preoperative Treatment.

BACKGROUND: Although patients with resectable colorectal liver metastasis (CLM), a population with good prognosis, have been treated with upfront surgery, some patients have had a poor prognosis. This study aimed to investigate biologic prognostic factors in patients with resectable CLMs. METHODS: This single-center retrospective study enrolled consecutive patients who underwent liver resection for initial CLMs at the Cancer Institute Hospital between 2010 and 2020. The study defined CLMs as resectable (tumor size < 5 cm; < 4 tumors; no extrahepatic metastasis) or borderline resectable (BR). Preoperative chemotherapy was administered to patients with BR CLMs. RESULTS: During the study period, 309 CLMs were classified as resectable without preoperative chemotherapy and 345 as BR with preoperative chemotherapy. For the 309 patients with resectable CLMs, the independent poor prognostic factors associated with overall survival in the multivariable analysis were high tumor marker levels (CEA ≥ 25 ng/mL and/or CA19-9 ≥ 50 U/mL; (hazard ratio [HR], 2.45; p = 0.0007), no adjuvant chemotherapy (HR, 1.69; p = 0.043), and age of 75 years or older (HR, 2.09; p = 0.012). The 5-year survival rates for the patients with high tumor marker (TM) levels (CEA ≥25 ng/mL and/or CA19-9 ≥50 U/mL) were significantly worse than for those with low TM levels (CEA < 25 ng/mL and CA19-9 < 50 U/mL) (55.3% vs. 81.1%; p <0.0001) and similar to the rate for those with BR CLMs (52.1%; p = 0.864). Postoperative adjuvant chemotherapy had an impact on prognosis only in the high-TM group (HR, 2.65; p = 0.007). CONCLUSIONS: High TM levels have a prognostic impact on patients with resectable CLMs stratified by tumor number and size. Perioperative chemotherapy improves long-term outcomes for patients with CLM and high TM levels.

Long-Term Postsurgical Outcomes of Neoadjuvant Chemoradiation (CROSS) Versus Chemotherapy (FLOT) for Multimodal Treatment of Adenocarcinoma of the Esophagus and the Esophagogastric Junction.

BACKGROUND: The question of the ideal neoadjuvant therapy for locally advanced esophagogastric adenocarcinoma has not been answered to date. Multimodal treatment has become a standard treatment for these adenocarcinomas. Currently, perioperative chemotherapy (FLOT) or neoadjuvant chemoradiation (CROSS) is recommended. METHODS: A monocentric retrospective analysis compared long-term survival after CROSS versus FLOT. The study enrolled patients with adenocarcinoma of the esophagus (EAC) or the esophagogastric junction type I or II undergoing oncologic Ivor-Lewis esophagectomy between January 2012 and December 2019. The primary objective was to determine the long-term outcome in terms of overall survival. The secondary objectives were to determine differences regarding the histopathologic categories after neoadjuvant treatment and the histomorphologic regression. RESULTS: The findings showed no survival advantage for one or the other treatment in this highly standardized cohort. All the patients underwent open (CROSS: 9.4% vs. FLOT: 22%), hybrid (CROSS: 82% vs. FLOT: 72%), or minimally invasive (CROSS: 8.9% vs. FLOT: 5.6%) thoracoabdominal esophagectomy. The median post-surgical follow-up period was 57.6 months (95% confidence interval [CI] 23.2-109.7 months), and the median survival was longer for the CROSS patients (54 months) than for the FLOT patients (37.2 months) (p = 0.053). The overall 5-years survival was 47% for the entire cohort (48% for the CROSS and 43% for the FLOT patients). The CROSS patients showed a better pathologic response and fewer advanced tumor stages. CONCLUSION: The improved pathologic response after CROSS cannot be translated into longer overall survival. To date, the choice of which neoadjuvant treatment to use can be made only on the basis of clinical parameters and the patient's performance status.

Does resection after neoadjuvant chemotherapy of docetaxel, oxaliplatin, and S-1 (DOS regimen) benefit for gastric cancer patients with single non-curable factor? a multicenter, prospective cohort study (Neo-REGATTA).

BACKGROUND: The Neo-REGATTA study evaluated the effectiveness and safety of Docetaxel, oxaliplatin, and S-1 (DOS regimen) followed by radical resection vs. chemotherapy in advanced gastric adenocarcinoma patients with single non-curable factor. METHODS: This cohort study prospectively enrolled advanced gastric adenocarcinoma patients with single non-curable factor between November 2017 and June 2021. Patients without progression after four cycles of DOS were divided into resection group and chemotherapy group. The outcomes included overall survival (OS), progression-free survival (PFS) and safety. Effectiveness analysis was also performed by propensity score matching (PSM). RESULTS: A total of 73 patients were enrolled and 13 patients were withdrawn due to disease progression after 4 cycles of DOS. Afterwards, 35 and 25 participants were in the resection and chemotherapy groups, respectively. After a median follow-up time of 30.0 months, the median PFS and OS were 9.0 months, and 18.0 months for the chemotherapy group, but not reached in the resection group. After PSM, 19 matched participants were in each group, and the median PFS and OS were longer in resection group than that in chemotherapy group. The most common grade 3 or 4 adverse events both in the resection group and chemotherapy groups were neutropenia (5.7%, 8.0%) and leukopenia (5.7%, 8.0%). CONCLUSIONS: Radical resection might provide survival benefit compared with continuous chemotherapy alone in advanced gastric adenocarcinoma patients who had a disease control after DOS, with a good safety profile. TRIAL REGISTRATION: The study protocol was registered on ClinicalTrial.gov (NCT03001726, 23/12/2016).

Perioperative TAS-118 plus oxaliplatin in patients with locally advanced gastric cancer: APOLLO-11 study.

BACKGROUND: We investigated the feasibility of perioperative chemotherapy with S-1 and leucovorin (TAS-118) plus oxaliplatin in patients with locally advanced gastric cancer. METHODS: Patients with clinical T3-4N1-3M0 gastric cancer received four courses of TAS-118 (40-60 mg/body, orally, twice daily for seven days) plus oxaliplatin (85 mg/m2, intravenously, day one) every two weeks preoperatively followed by gastrectomy with D2 lymphadenectomy, followed by postoperative chemotherapy with either 12 courses of TAS-118 monotherapy (Step 1) or eight courses of TAS-118 plus oxaliplatin (Step 2). The primary endpoints were completion rates of preoperative chemotherapy with TAS-118 plus oxaliplatin and postoperative chemotherapy with TAS-118 monotherapy (Step 1) or TAS-118 plus oxaliplatin (Step 2). RESULTS: Among 45 patients enrolled, the preoperative chemotherapy completion rate was 88.9% (90% CI 78.0-95.5). Major grade ≥ 3 adverse events (AEs) were diarrhoea (17.8%) and neutropenia (8.9%). The R0 resection rate was 95.6% (90% CI 86.7-99.2). Complete pathological response was achieved in 6 patients (13.3%). Dose-limiting toxicity was not observed in 31 patients receiving postoperative chemotherapy (Step 1, n = 11; Step 2, n = 20), and completion rates were 90.9% (95% CI 63.6-99.5) for Step 1 and 80.0% (95% CI 59.9-92.9) for Step 2. No more than 10% of grade ≥ 3 AEs were observed in patients receiving Step 1. Hypokalaemia and neutropenia occurred in 3 and 2 patients, respectively, receiving Step 2. The 3-year recurrence-free and overall survival rates were 66.7% (95% CI 50.9-78.4) and 84.4% (95% CI 70.1-92.3), respectively. CONCLUSIONS: Perioperative chemotherapy with TAS-118 plus oxaliplatin with D2 gastrectomy is feasible.

Role of perioperative chemotherapy and radiotherapy for localized high-grade malignant peripheral nerve sheath tumor at the extremities and trunk wall: a population-based cohort study.

BACKGROUND: Primary tumor resection is the mainstay of treatment for malignant peripheral nerve sheath tumors. However, the efficacy of perioperative chemotherapy and radiotherapy for malignant peripheral nerve sheath tumors has not been elucidated. METHODS: This retrospective analysis based on a Japanese registry included patients with localized malignant peripheral nerve sheath tumors arising at the extremities and trunk wall. Disease-specific overall survival and local recurrence-free survival were estimated using the Kaplan-Meier method. A Cox regression model was used to identify prognostic factors. Characteristics of groups with or without chemotherapy were adjusted using propensity score matching. RESULTS: In total, 291 patients were included. The 5-year disease-specific overall survival rate was 70.6%. Multivariate analysis of disease-specific overall survival revealed that deep-seated tumors were a poor prognostic factor, but perioperative chemotherapy was not associated with disease-specific overall survival (hazard ratio, 0.81; 95% confidence interval, 0.45-1.43, P = 0.46). Local recurrence was observed in 55 patients (19.0%), and surgical margins (R1 and R2) were significant risk factors. Overall, perioperative chemotherapy did not prolong disease-specific overall survival (5-year disease-specific overall survival: 74.1% vs. 69.3%, P = 0.75) and had limited efficacy in the group with tumor size ≥ 5 cm, although the difference was not statistically significant (5-year disease-specific overall survival: 77.2% vs. 68.6%, respectively, P = 0.13). After adjustment by propensity score matching, perioperative chemotherapy significantly prolonged disease-specific overall survival (5-year disease-specific overall survival: 74.9% vs. 57.1%, P = 0.03), but this effect was not observed in local recurrence-free survival. In all patients, perioperative radiotherapy did not correlate with local recurrence-free survival (hazard ratio, 1.43; 95% confidence interval 0.78-2.62, P = 0.25). CONCLUSIONS: Perioperative chemotherapy had limited efficacy for disease-specific overall survival in patients with localized malignant peripheral nerve sheath tumors.

Perioperative chemotherapy with 5-FU, leucovorin, oxaliplatin, and docetaxel (FLOT) for esophagogastric adenocarcinoma: ten years real-life experience from a surgical perspective.

PURPOSE: According to the results of FLOT4 trial, perioperative FLOT chemotherapy improved overall survival (OS) in locally advanced, resectable esophagogastric adenocarcinoma (EGA) compared to perioperative ECF/ECX. We report real-life data 10 years after introduction of perioperative FLOT at our institution. METHODS: Survival of 356 consecutive EGA patients (cT3/4 and/or cN + and/or cM1) who underwent curative surgical resection was retrospectively analysed from a prospective database. A total of 263 patients received preoperative chemotherapy according to FLOT protocol and 93 patients received an epirubicin/platinum/5FU-based regimen (EPF). Propensity score matching (PSM) according to pretretment characteristics was performed to compensate for heterogeneity between groups. RESULTS: Median OS did not differ between groups (FLOT/EPF 52.1/46.4 months, p = 0.577). After PSM, survival was non-significantly improved after FLOT compared to EPF (median OS not reached/46.4 months, p = 0.156). Perioperative morbidity and mortality did not differ between groups. Histopathologic response rate was 35% after FLOT and 26% after EPF (p = 0.169). R0 resection could be achieved more frequently after FLOT than after EPF (93%/79%, p = 0.023). CONCLUSION: Overall survival after perioperative FLOT followed by surgery is comparable to clinical trials. However, collective real-life application of FLOT failed to provide a significant survival benefit compared to EPF. In clinical reality, patient selection is triggered by age, comorbidity, tumor localization, and clinical tumor stage. Yet matched analyses support FLOT4 trial findings.

Comparison of the effects of perioperative and adjuvant chemotherapy on outcomes of operable gastric cancer: A retrospective cohort experience from a tertiary cancer center.

OBJECTIVE: To compare the overall survival and disease-free survival rates with perioperative or adjuvant chemotherapy regimens in operable gastric cancer cases. METHODS: The retrospective, observational study was conducted at the Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, and comprised date from January 2015 to December 2020 of operable gastric cancer patients who had perioperative or adjuvant chemotherapy. Overall survival and disease-free survival were evaluated. Data was analysed using SPSS 23. RESULTS: Of the 108 patients in the aga range 27-80 years, 71(65.74%) were males. The overall median age was 49.50 years (interquartile range: 28 years). There were 69(63.88%) patients on perioperative and 39(36.12%) on adjuvant chemotherapy. The probability of 2- and 3-year overall survival was 68.20% and 57.32% in the perioperative group, and 51.09% and 45.43%, respectively, in the adjuvant group. The probability of 2- and 3-year disease-free survival was 55.45% and 49.30% in the perioperative group, while 2-year disease-free survival was 38.39% in the adjuvant group which had no patient reaching the 3-year mark. The median overall survival for the perioperative group was 49.29 months (interquartile range: 44.50 months) and for the adjuvant group it was 28.23 months (interquartile range: 25.00months) (p=0.07). The median disease-free survival was 35.46 months (interquartile range: 38.50 months) for the perioperative group and 10.19 months (interquartile range: 14.00months) for adjuvant group (p=0.16). The difference between the groups was not significant (p>0.05), but there was a trend suggestive of the superiority of perioperative chemotherapy over adjuvant chemotherapy. CONCLUSIONS: In operable gastric cancer cases, the difference between the groups was not significant, but there was a trend suggestive of the superiority of perioperative chemotherapy over adjuvant chemotherapy with respect to overall survival and disease-free survival.

Three-Year Outcomes of a Phase II Study of Perioperative Capecitabine Plus Oxaliplatin Therapy for Clinical SS/SE N1-3 M0 Gastric Cancer (OGSG 1601).

BACKGROUND: We previously reported the good feasibility and favorable efficacy of perioperative capecitabine plus oxaliplatin (CapeOx) in patients (pts) with clinical T3(SS)/T4a(SE) N1-3 M0 gastric cancer (GC) in a phase II study in which the pathological response rate, the primary endpoint, of 54.1% was demonstrated. Here, we report 3-year follow-up data. METHODS: The eligibility criteria included clinical T3(SS)/T4a(SE) N1-3 M0 GC according to the Japanese Classification of Gastric Carcinoma-3rd English Edition (JCGC). Three cycles of neoadjuvant CapeOx (capecitabine, 2000mg/m2 for 14 days; oxaliplatin, 130mg/m2 on day 1, every 3 weeks) were administered, followed by 5 cycles of adjuvant CapeOx after D2 gastrectomy. Three-year overall survival and relapse-free survival are presented here, and analyzed by cohorts based on pathologic response rate (pRR). RESULTS: Thirty-seven pts were enrolled from July 2016 to May 2017, and fully evaluated for efficacy and toxicity. Thirty-three pts (89.2%) completed the planned three cycles of neoadjuvant CapeOx and underwent gastrectomy, with an R0 resection rate of 78.4% (n = 29). The overall survival (OS) rate and relapse-free survival (RFS) rate at 3 years was 83.8% (95% CI, 72.7-96.5%) and 73.0% (95% CI, 60.0-88.8%), respectively. Further, the 3-year OS rate in pts with pathological response of grade 1a (n = 13) and grade 1b or higher (n = 20) was 69.2% (95% CI: 48.2-99.5%) and 100.0%, respectively, based on JCGC. Pathological response rate was classified according to JCGC as follows: grade 0, the tumor was not affected; grade 1a, less than one-third of the tumor was affected; grade 1b, one to two thirds of the tumor was affected; grade 2, greater than or equal to two thirds was affected; and grade 3, no residual tumor. A pathological response was defined as grade 1b or greater. CONCLUSION: Perioperative CapeOx showed good feasibility and favorable prognosis, especially in pts with pathological response of grade 1b or higher and was found to be useful in predicting prognosis. The data obtained using this novel approach warrant further investigation (Trial ID: UMIN000021641, jRCTs051180109).

Real-world evidence on perioperative chemotherapy in localized soft tissue sarcoma of the extremities and trunk wall; a population-based study.

BACKGROUND: Data from the real-world setting on perioperative chemotherapy in high-risk, localized soft tissue sarcoma (STS) is limited. Real-world data (RWD) includes data derived from patients treated outside clinical trials and often captures long-term follow-up not recorded in clinical trials. The aim of this study was to provide population-based, real-world evidence on perioperative chemotherapy in localized STS. MATERIAL AND METHODS: Adult patients with localized STS in the extremities or trunk wall treated at Oslo University Hospital, Oslo, Norway from 1998 to 2017 were included in the study. Data were extracted from a prospectively maintained database, supplemented by retrospective review of medical records. RESULTS: The total study cohort included 806 patients, of whom 154 (19%) received perioperative chemotherapy. A regimen with anthracycline and ifosfamide was given in 141 of 154 cases (92%). During long-term follow-up two patients developed secondary malignancies, cardiac toxicity was registered in 11 patients (7%) and renal toxicity in 12 patients (8%). Seventy-one of 154 patients (46%) were treated outside of clinical trials and constituted the RWD cohort. The median age at surgery was slightly lower and there were more synovial sarcomas and fewer myxofibrosarcomas in the RWD cohort. No difference in chemotherapy dose intensity was observed. The estimated 5-year metastasis-free survival (MFS) in all patients receiving perioperative chemotherapy was 58%. In the RWD cohort 5-year MFS was 53% and in the clinical study cohort 61% (HR 1.24; 95% CI 0.77-2.00). CONCLUSION: Long-term outcome after perioperative chemotherapy was comparable for patients treated in routine clinical practice to those in clinical trials. Secondary malignancy and cardiac toxicity were observed. The risk of serious late side effects should be included in the decision process on perioperative chemotherapy.

A randomized controlled trial comparing perioperative vs. postoperative mFOLFOX6 for lower rectal cancer with suspected lateral pelvic lymph node metastasis (JCOG1310): a phase II/III randomized controlled trial.

OBJECTIVE: The optimal perioperative chemotherapy for lower rectal cancer with lateral pelvic lymph node metastasis remains unclear. We evaluated the efficacy and safety of perioperative mFOLFOX6 in comparison with postoperative mFOLFOX6 for rectal cancer patients undergoing total mesorectal excision with lateral lymph node dissection. METHODS: We conducted an open label randomized phase II/III trial in 18 Japanese institutions. We enrolled patients with histologically proven lower rectal adenocarcinoma with clinical pelvic lateral lymph node metastasis who were randomly assigned (1:1) to receive postoperative mFOLFOX6 (12 courses of intravenous oxaliplatin [85 mg/m2] with L-leucovorin [200 mg/m2] followed by 5-fluorouracil [400 mg/m2, bolus and 2400 mg/m2, continuous infusion, repeated every 2 weeks]) or perioperative mFOLFOX6 (six courses each preoperatively and postoperatively). The primary endpoint was overall survival (OS). The trial is registered with Japan Registry of Clinical Trials, number jRCTs031180230. RESULTS: Between May 2015, and May 2019, 48 patients were randomized to the postoperative arm (n = 26) and the perioperative arm (n = 22). The trial was terminated prematurely due to poor accrual. The 3-year OS in the postoperative and perioperative groups were 66.1 and 84.4%, respectively (HR 0.58, 95% CI [0.14-2.45], one-sided P = 0.23). The pathological complete response rate in the perioperative group was 9.1%. Grade 3 postoperative surgical complications were more frequently observed in the perioperative arm (50.0 vs. 12.0%). One treatment-related death due to sepsis from pelvic infection occurred in the postoperative group. CONCLUSIONS: Perioperative mFOLFOX6 may be an insufficient treatment to improve survival of lower rectal cancer with lateral pelvic lymph node metastasis.

A randomized controlled trial of surgery and postoperative modified FOLFOX6 versus surgery and perioperative modified FOLFOX6 plus cetuximab in patients with KRAS wild-type resectable colorectal liver metastases: EXPERT study.

PURPOSE: To clarify the efficacy of perioperative chemotherapy for the patients with resectable colorectal liver metastases (CLM), we conducted a multicenter randomized phase III trial to compare surgery followed by postoperative FOLFOX regimen with perioperative FOLFOX regimen plus cetuximab in patients with KRAS wild-type resectable CLM. METHODS: Patients who had KRAS wild-type resectable CLM having one to eight liver nodules without extrahepatic disease were randomly assigned to the postoperative chemotherapy group, wherein up-front hepatectomy was performed followed by 12 cycles of postoperative modified FOLFOX6, and the perioperative chemotherapy group (experimental), wherein six cycles of preoperative modified FOLFOX6 plus cetuximab were performed followed by hepatectomy and six cycles of postoperative modified FOLFOX6 plus cetuximab. The primary endpoint was progression-free survival (PFS). RESULTS: There were 37 patients in postoperative chemotherapy group and 40 patients in the perioperative chemotherapy group who were analyzed. Baseline characteristics were well-balanced between groups. The PFS and overall survival (OS) showed no significant difference (PFS, hazard ratio 1.18 [95% confidence interval 0.69-2.01], P = 0.539: OS, 1.03 [0.46-2.29], P = 0.950). In the postoperative chemotherapy group, 35.1% had a 3-year PFS, and 86.5% had a 3-year OS. Meanwhile, in the perioperative chemotherapy group, 30.0% had a 3-year PFS, and 74.4% had a 3-year OS. CONCLUSION: There was no difference in survival found between the group of the perioperative chemotherapy plus cetuximab and that of the postoperative chemotherapy in the cohort of our study. The study was registered in the University Hospital Medical Information Network (UMIN000007787).