Efficacy Of Preoperative Chemotherapy Research Articles

Number of Healthy Teeth Can Predict the Response of Rectal Cancer to Chemoradiotherapy: A Retrospective Study.

It has been reported that the oral and gut microbiomes are associated with the prognosis in patients who undergo surgery, chemotherapy, and radiation for colorectal cancer. This study is the first to identify a correlation between the number of healthy teeth, which is an oral health indicator, and the efficacy of preoperative chemotherapy for rectal cancer. This retrospective single-center study included 30 patients who underwent radical surgery after preoperative chemoradiotherapy (CRT) between December 2013 and June 2021. The relationship between number of teeth before CRT and the efficacy of CRT, CRT-related adverse events, postoperative complications, and long-term postoperative outcomes was examined. The number of healthy teeth was significantly greater in patients with downstaging of their disease than in those without downstaging (P = .027) and in patients with a complete response according to the Response Evaluation Criteria in Solid Tumors than in those who did not have a complete response (P = .014). Patients were divided into two groups according to whether they had ≥15 teeth or ≤14 teeth. There was no significant between-group difference in CRT-related adverse events. The incidence of all postoperative complications and grade II postoperative complications tended to be higher in patients with ≥15 teeth (P = .071 and P = .092, respectively), as did the 5-year overall survival rate (P = .083) and the 5-year disease-free rate (P = .007). The number of healthy teeth predicted the response to preoperative CRT, postoperative complications, and the outcome of subsequent surgery in patients with rectal cancer.

Prognostic Role of Preoperative Chemotherapy in Liver-Limited Metastasis from Gastric Cancer.

We investigated the prognostic role of preoperative chemotherapy in patients who underwent hepatectomy for liver-limited metastasis (LLM) from gastric cancer (GC). A retrospective analysis was conducted for 52 consecutive patients who underwent macroscopically complete (R0 or R1) resection for synchronous or metachronous LLM from GC. Of the 52 patients, 18 (35%) received preoperative chemotherapy (PC group), while 34 (65%) underwent upfront surgery (US group). The PC group had a significantly longer overall survival than the US group (cumulative 5-year OS rate: 47.6% vs. 24.8%, p = 0.041). Multivariate analysis of OS revealed that preoperative chemotherapy was an independent favorable prognostic factor (hazard ratio: 0.445, p = 0.036). Patients showing a partial response to preoperative chemotherapy on RECIST had an improved OS compared with those exhibiting stable or progressive disease after preoperative chemotherapy and with US (p = 0.025), even among those with solitary LLM (p = 0.062) and multiple LLM (p = 0.026). At recurrence after hepatectomy for LLM, the PC group had a significantly higher incidence of solitary tumors than the US group (p = 0.043) and had a higher chance to undergo surgical resection for recurrent sites (p = 0.006). Preoperative chemotherapy can be recommended for patients with LLM from GC. The evaluation of the efficacy of preoperative chemotherapy offers additional information to determine the surgical indication for LLM.

Survival of GEJ and gastric adenocarcinoma patients admitted at Imam Khomeini and Aram oncology clinic and treated with preoperative EOX chemotherapy

Objective: We aimed to investigate safety and efficacy of preoperative chemotherapy using EOX regime in patients with locally advanced gastric and GEJ cancer who were admitted at Imam-Khomeini Oncology clinic and Aram clinic.
 Method: We performed a mix-cohort study in 51 gastric cancer patients. In the beginning, we performed contrast thorax and abdominal CT scan or ECO cardiograph to determine cancer staging. After that, each patient received 3-weeks EOX regime in 6 cycle. After each three cycles follow-up CT scan was performed to assess any possible progression. Response to the treatment, Overall survival, and Progression-Free Survival were the main outcomes that we evaluated in the current study. We used Kaplan-Meier approach and Cox regression to address survival rate and its prognostic factors
 Results: Overall, 72.5% percent were male and mean age of study participants was 57.6. Complete response rate was observed in 11.1%, while 51.1% showed partial response. Median of overall survival and Progression-Free Survival was estimated 35.0 and 28.0 month, respectively. The 5-year overall survival was 74.2% and for PFS it was estimated at 57.7%.
 Conclusion: Preoperative chemotherapy using EOX regime could increase survival rate among patients with gastric and GEJ cancer.

Safety and efficacy of preoperative chemotherapy for muscle-invasive bladder cancer in elderly patients.

This study aimed at describing the feasibility and oncological outcomes of standard cisplatin-based neoadjuvant chemotherapy (C-NAC) for muscle-invasive bladder cancer (MIBC) in patients aged ≥ 75 and assess the impact of baseline geriatric parameters. This retrospective study included patients with stage cT2-4NanyM0 MIBC aged 75 and older treated with ≥ 1 cycle of C-NAC from 2011 to 2021 at a high-volume academic center. Primary outcome was overall survival (OS). Secondary outcomes were chemotherapy feasibility (administration of ≥ 4 cycles), safety, and pathological downstaging. Fifty-six patients were included. Median age was 79 (range 75-90). C-NAC regimen was ddMVAC in 41 patients and GC in 15. Seventy-three percent of patients received ≥ 4 cycles of C-NAC. Grade ≥ 3 toxicity was observed in 55% of patients. The febrile neutropenia rate was 7%. Thirty patients underwent cystectomy, and 13 underwent chemoradiotherapy. Three-year OS was 63%. Geriatric parameters polypharmacy, undernutrition, and age-adjusted Charlson comorbidity index ≥ 8 predicted worse OS. Standard-of-care C-NAC and local treatments are feasible in selected elderly MIBC patients, with efficacy and safety findings similar to that observed in pivotal trials with younger patients. The prognostic impact of geriatric parameters underlines the need for specialized evaluation before treatment initiation.

Significance of Desmoplastic Histopathological Growth Pattern for Colorectal Liver Metastases Treated With Preoperative Chemotherapy.

The aim of this study was to evaluate hepatectomy cases that underwent preoperative chemotherapy to examine the relationship between the development of desmoplastic histopathological growth pattern (dHGP) and prognosis and recurrence and determine whether it is useful for evaluating preoperative chemotherapy. A total of 133 cases with hepatic metastasis for colorectal cancer that underwent surgical resection. Of the 102 cases that underwent preoperative chemotherapy, 34 (33%) were determined to be dHGP positive, which was statistically significantly higher than the 2 of 31 cases (6.5%) that had not undergone preoperative chemotherapy. Regarding the 5-year recurrence-free survival, the dHGP group had a value of 50.3%, whereas the non-dHGP group had a value of 7.1%. For the 5-year overall survival, the dHGP group had a better prognosis than the non-dHGP group (57.6% vs. 37.1%, respectively), with a statistically significant difference. Univariate analysis of recurrence-free survival showed that the number of tumours, the Response Evaluation Criteria in Solid Tumors, and the presence or absence of dHGP were prognostic factors, whereas multivariate analysis showed that the presence or absence of dHGP was an independent prognostic factor. Univariate analysis of the overall survival showed that the number of tumours, the Response Evaluation Criteria in Solid Tumors, and presence or absence of dHGP were prognostic factors. Multivariate analysis showed that the presence or absence of dHGP was an independent prognostic factor. dHGP is useful as a new evaluation method for evaluating the efficacy of preoperative chemotherapy.

Dynamics of the prognostic nutritional index in preoperative chemotherapy in patients with colorectal liver metastases

BackgroundIdentifying the prognostic indicators that reflect the efficacy of preoperative chemotherapy is necessary. In this study, we investigated the prognostic indicators targeting the systemic inflammatory response for the administration of preoperative chemotherapy in patients with colorectal liver metastases. MethodsData for 192 patients were retrospectively analyzed. The relationship between overall survival and clinicopathological variables, including biomarkers such as the prognostic nutritional index, was investigated in patients who underwent upfront surgery or preoperative chemotherapy. ResultsIn the upfront surgery group, extrahepatic lesion (p=0.01) and low prognostic nutritional index (p < 0.01) were significant prognostic indicators, whereas a decrease in the prognostic nutritional index (p=0.01) during preoperative chemotherapy were independent poor prognostic factors in the preoperative chemotherapy group. In particular, a decrease in the prognostic nutritional index was a significant prognostic marker in patients aged <75 years (p=0.04). In patients with a low prognostic nutritional index aged <75 years, preoperative chemotherapy significantly prolonged overall survival (p=0.02). ConclusionA decrease in the prognostic nutritional index during preoperative chemotherapy predicted overall survival of patients with colorectal liver metastases after hepatic resection, and preoperative chemotherapy may be effective for patients aged <75 years with a low prognostic nutritional index.

A phase II study of preoperative chemotherapy with docetaxel, oxaliplatin, and S-1 followed by gastrectomy with D2 plus para-aortic nodal dissection for gastric cancer with extensive lymph node metastasis: JCOG1704.

354 Background: Prognosis of gastric cancer (GC) with extensive lymph node metastasis (ELM) is poor due to unresectability even without distant metastases. We conducted a phase II study to evaluate the safety and efficacy of preoperative chemotherapy with docetaxel (D), oxaliplatin (O), and S-1 (S) followed by extended gastrectomy. Methods: Eligibility criteria included histologically proven adenocarcinoma of the stomach; bulky nodal involvement around major branched arteries to the stomach (Bulky N) and/or para-aortic nodal metastases (PAN); cM0 (except para-aortic nodes); negative lavage cytology; not linitis plastica type; PS of 0 or 1; 20-75 years old. Patients received three 21-day cycles of preoperative chemotherapy of D (40 mg/m2 on day 1), O (100 mg/m2 on day 1), and S (80-120 mg /body from day 1 to day 14), and then underwent gastrectomy with D2 plus para-aortic nodal dissection. After surgery, patients received adjuvant chemotherapy with S-1 for 1 year. Primary endpoint was major pathological response rate, defined by the disappearance of more than two-thirds of the primary tumor. Expected and threshold value of major pathological response was set at 40% and 25%, respectively. Sample size was calculated to be 50 based on a one-sided alpha of 0.1, power of 0.8 and single-arm phase II study using a Southwest Oncology Group (SWOG) two-stage design. Results: Between Oct 2018 and Mar 2022, 47 patients were enrolled, of whom 46 were eligible for efficacy analysis. The median age was 67 years. The pathological type was differentiated in 33 patients and undifferentiated in 14. Twenty patients had only bulky N, 17 had only PAN, and 10 had both of bulky N and PAN. Clinical stage was III in 19 and IV in 28 patients. Except one patient refused chemotherapy, 46 patients (45 in three cycles and 1 in one cycle) completed preoperative DOS. Forty-four patients (94%) underwent gastrectomy, including 23 distal gastrectomy and 21 total gastrectomy, and 43 (91%) had an R0 resection. Major pathological response was confirmed in 26 of 46 patients (57% with 80% CI: 46-67), including pCR of 24%, which met the statistical significance (p&lt;0.0001). According to the Becker’s criteria, grade 3 was 13, grade 2 was 12, grade 1b was 7, and grade 1a was 11. DOS-related grade 3/4 toxicities included neutropenia in 11 patients (24%), anorexia in 7 (16%), diarrhea in 4 (9%), and febrile neutropenia in 4 (9%). Surgery-related grade 3/4 toxicities were abdominal abscess in 5 (12%) and pancreatic fistula in 3 (7%). No treatment-related death was observed. Conclusions: Preoperative DOS followed by gastrectomy with D2 plus para-aortic nodal dissection is safe, feasible, and effective for GC with ELM. Clinical trial information: jRCTs031180028 .

Evaluating Neoadjuvant Chemotherapy for Lower Esophageal Squamous Cell Carcinoma by Measuring Esophageal Wall Thickness.

The aim of this study was to evaluate the efficacy of preoperative chemotherapy for stage II-III esophageal squamous cell carcinoma based on an objective computed tomography method. A total of 82 patients who underwent preoperative chemotherapy followed by surgery for advanced esophageal squamous cell carcinoma from January 2006 to June 2019 were included. Treatment effect was evaluated by measuring the esophageal wall thickness before and after neoadjuvant chemotherapy using contrast-enhanced thoracoabdominal computed tomography. The percentage decrease in esophageal wall thickness was calculated using the following formula: reduction (%)=(wall thickness before preoperative chemotherapy - wall thickness after preoperative chemotherapy)/(wall thickness before preoperative chemotherapy)×100. We demonstrated the efficacy of this measurement method and then analyzed which patient factors might affect the treatment effect. Receiver operating characteristic analysis showed the percentage tumor reduction to be a good predictor of histological therapeutic effect (grade ≥2) (area under the curve=0.727). In the multivariate analysis, tumor location (lower versus upper esophagus) was identified as an independent factor associated with tumor reduction (odds ratio=0.15; 95% confidence interval=0.03-0.79; p=0.025). We demonstrated an association between the reduction of esophageal wall thickness in the tumoral area and the histological therapeutic effect of chemotherapy. Secondary analysis showed poorer tumor reduction in patients with lower esophageal cancer than in those with upper esophageal cancer.

Protocol digest of a phase III trial to evaluate the efficacy of preoperative chemotherapy with S-1 plus oxaliplatin followed by D2 gastrectomy with postoperative S-1 in locally advanced gastric cancer: Japan Clinical Oncology Group study JCOG1509 (NAGISA Trial)

Abstract In Japan, postoperative chemotherapy is a standard care for stage II/III gastric cancer after curative resection with D2 lymph node dissection, and the clinical outcomes of patients with stage III gastric cancer are unsatisfactory. A combination of oral S-1 and oxaliplatin, that is the standard chemotherapy regimen for unresectable advanced/recurrent gastric cancer associated with a high response rate, was considered the most promising preoperative chemotherapy regimen. This randomized phase III trial was started in September 2016 to confirm the superiority of preoperative chemotherapy with S-1 plus oxaliplatin followed by D2 gastrectomy with postoperative chemotherapy compared with D2 gastrectomy with postoperative chemotherapy for patients with clinical T3–4N1–3 M0 locally advanced gastric cancer in terms of overall survival. A total of 470 patients will be enrolled from 63 hospitals in Japan for 8.5 years. This trial has been registered in the Japan Registry of Clinical Trials as jRCTs031180350 [https://jrct.niph.go.jp/latest-detail/jRCTs031180350].

Development of a Nomogram for Predicting the Efficacy of Preoperative Chemotherapy in Osteosarcoma.

BackgroundDue to the obvious heterogeneity of osteosarcoma, many patients are not sensitive to neoadjuvant chemotherapy. In this study, the clinical characteristics and auxiliary examinations of patients with osteosarcoma were used to predict the effect of preoperative chemotherapy, so as to guide the clinical adjustment of the treatment plan to improve the prognosis of patients.MethodsIn this study, 90 patients with pathologically confirmed osteosarcoma were included, and they were randomly divided into training cohort (n=45) and validation cohort (n=45). A prediction model of preoperative chemotherapy efficacy for osteosarcoma was established by multivariate logistic regression analysis, and a nomogram was used as the visualization of the model. The ROC curve and C-index were used to evaluate the accuracy of the nomogram. Decision curve analysis (DCA) was used to evaluate the net benefit of the nomogram in predicting the efficacy of neoadjuvant chemotherapy under different threshold probabilities.ResultsIn the study, the age, gender, location, tumor volume, metastasis at the first visit, MSTS staging, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) were used in the multivariate logistic regression analysis and the construction of the nomogram. The AUC and C-index of the training cohort were 0.793 (95% CI: 0.632, 0.954) and 0.881 (95% CI: 0.776, 0.986), respectively. The AUC and C-index in the validation cohort were 0.791 (95% CI: 0.644, 0.938) and 0.813 (95% CI: 0.679, 0.947), respectively, which were close to the training cohort. DCA showed that the model had good clinical application value.ConclusionBased on the clinical characteristics of patients and auxiliary examinations, the nomogram can be good used to predict the efficacy of preoperative chemotherapy for osteosarcoma.

Impact of preoperative chemotherapy as initial treatment for advanced gastric cancer with peritoneal metastasis limited to positive peritoneal lavage cytology (CY1) or localized peritoneal metastasis (P1a): a multi-institutional retrospective study.

Gastric cancer (GC) patients with peritoneal metastasis are defined as stage IV in the Japanese classification of GC. For patients with peritoneal metastasis limited to positive peritoneal lavage cytology (CY1) and/or localized peritoneal metastasis (P1a), gastrectomy followed by S1 monotherapy is one of the most widely accepted therapeutic strategy in Japan. This study investigated the efficacy of preoperative chemotherapy as initial treatment in GC patients with CY1 and/or P1a. We retrospectively reviewed GC patients diagnosed with CY1 and/or P1a at 34 institutions in Japan between 2008 and 2012. Selection criteria were: adenocarcinoma, no distant metastasis except CY1 or P1a, and no prior treatment. The subjects were divided into an Initial-Chemotherapy group and an Initial-Surgery group, according to the initial treatment. A total of 824 patients were collected and 713 eligible patients were identified for this study. As the initial treatment, 150 patients received chemotherapy (Initial-Cx), and 563 patients underwent surgery (Initial-Sx). Initial-Cx regimens were cisplatin plus S1/docetaxel plus cisplatin plus S1/others (n = 90/37/23). Both overall survival (OS) and progression-free survival (PFS) were similar between the Initial-Cx and Initial-Sx groups (median OS 24.8 and 24.0months, HR 1.07, 95% CI 0.87-1.3; median PFS 14.9 and 13.9months, HR 1.04, 95% CI 0.85-1.27). The 5-year OS rates were 22.3% in the Initial-Cx group and 21.5% in the Initial-Sx group. Although, the preoperative chemotherapy did not show a survival benefit for GC patients with CY1 and/or P1a, initial-Cx showed favorable survival in patients who converted to P0 and CY0.

Influence of preoperative chemotherapy-induced leukopenia on survival in patients with esophageal squamous cell carcinoma: exploratory analysis of JCOG9907.

The relationship between chemotherapy-induced leukopenia (CIL) and survival has not been investigated in patients undergoing preoperative chemotherapy for esophageal squamous cell carcinoma (ESCC). We analyzed the association of CIL with survival outcomes using data from JCOG9907 on the efficacy of preoperative chemotherapy for stage II/III ESCC. Preoperative chemotherapy consisted of two courses of 5-FU (800mg/m2 days 1-5) and cisplatin (80mg/m2 day 1) repeated every 3weeks. Patients in the preoperative chemotherapy arm receiving at least one course of chemotherapy and undergoing subsequent surgery in JCOG9907 were divided into two subgroups: CIL ( +), those with grade 2-4 leukopenia at least once during preoperative chemotherapy; and CIL (-), those with grades 0-1. The association of CIL with overall survival (OS) and progression-free survival (PFS) was analyzed. Among 164 patients enrolled in JCOG9907, 152 patients were included in this analysis, 52 in CIL ( +) and 100 patients in CIL (-) subgroups. The 3-year OS for CIL ( +) was inferior to that for CIL (-) (48.1% vs. 73.9%); hazard ratio (HR) = 1.94 (95% CI 1.18-3.16, P < .01). For 3-year PFS, a similar tendency was observed (44.2% vs. 55.8%; HR = 1.38 (95% CI 0.88-2.17, P = .16). Multivariable analysis revealed that CIL was not an independent factor for OS (HR = 1.14, 95% CI 0.63-2.07, P = .67). We showed that CIL during preoperative chemotherapy might not be a prognostic factor in patients with ESCC.

Efficacy of Preoperative Chemotherapy for High Risk Upper Tract Urothelial Carcinoma.

The impact of preoperative chemotherapy in patients with upper urinary tract urothelial carcinoma remains poorly investigated. We assessed the rates of pathological complete response (pT0N0/X) and downstaging (pT1N0/X or less) at radical nephroureterectomy after preoperative chemotherapy and evaluated their impact on survival. This was an international observational study of patients who underwent preoperative chemotherapy and radical nephroureterectomy for high risk upper tract urothelial carcinoma between 2005 and 2017. Multiple imputation of chained equations was applied to account for missing values. Logistic regression analyses were performed to identify predictors of pathological response. Cox proportional hazard regression models were used to estimate recurrence-free survival, cancer specific survival and overall survival. A total of 267 patients met our inclusion criteria. Among included patients 82 (31%) received methotrexate, vinblastine, doxorubicin and cisplatin; 123 (46%) gemcitabine and cisplatin; 25 (9%) gemcitabine and carboplatin; and 32 (12%) other regimens. The overall rates of pathological complete response and pathological downstaging were 10.1% and 44.9%, respectively. On multivariable analysis the use of gemcitabine and cisplatin, and gemcitabine and carboplatin was not statistically different from methotrexate, vinblastine, doxorubicin and cisplatin in achieving pathological complete response and pathological downstaging, respectively. The number of administered cycles did not appear to have an effect on pathological responses. Pathological downstaging was the strongest prognostic factor for recurrence-free survival (HR 0.2, p <0.001), cancer specific survival (HR 0.19, p <0.001) and overall survival (HR 0.40, p <0.001). Pathological downstaging after preoperative chemotherapy is a robust prognostic factor at radical nephroureterectomy and is associated with improved survival outcomes. Although preoperative chemotherapy appears to be effective, well designed prospective studies are still needed.

Long Term Efficacy of Preoperative Chemotherapy or Chemoradiotherapy Combined with Total Mesorectal Excision for Locally Advanced Rectal Cancer: Retrospective Analysis of 305 Patients

Long Term Efficacy of Preoperative Chemotherapy or Chemoradiotherapy Combined with Total Mesorectal Excision for Locally Advanced Rectal Cancer: Retrospective Analysis of 305 Patients

Phase II trial of preoperative sequential chemotherapy followed by chemoradiotherapy for high-risk gastric cancer

Background and purposeTo evaluate the safety and efficacy of preoperative chemotherapy (CTx) followed by chemoradiotherapy (CCRT) for high-risk gastric cancer (GC). Methods and materialsThe inclusion criteria were as follows: (1) Borrmann type 4; (2) large Borrmann type 3 (≥8 cm); (3) single bulky (≥3 cm × 1) or multiple lymph nodes (≥1.5 cm × 3). Patients received two 21-day courses of induction CTx of TS-1 (35 mg/m2, p.o, twice daily on days 1–14), docetaxel (30 mg/m2, i.v., days 1 and 8), and cisplatin (30 mg/m2, i.v., days 1 and 8) followed by CCRT (two courses of TS-1 and cisplatin in combination with 45 Gy radiation). ResultsForty-two patients were enrolled between March 2014 and February 2016, and 39 of these completed sequential CTx and CCRT. Among the 33 patients who underwent R0 resection, the pathologic response rate was 39.4% [no residual carcinoma (n = 5, 15.2%), with 1–10% residual carcinoma (n = 8, 24.2%)]. Overall, 4 patients (12.1%) were pathologic stage 0, 7 (21.2%) were stage I, 10 (30.3%) were stage II, and 12 (36.4%) were stage III. The overall survival rate at 3 years was 77.9% for stages 0 and I, 66.8% for stages II–III, and 33.3% for unresectable cases (P = 0.001). Toxicity was mild to moderate with grade 4 neutropenia (n = 1) and neutropenic fever (n = 1) as the most prominent side-effects. ConclusionsSequential CTx and CCRT prior to surgery are feasible and effective for high-risk GC.Trial registration number: NCT02495493.

Neoadjuvant Chemotherapy With mFOLFOXIRI Without Routine Use of Radiotherapy for Locally Advanced Rectal Cancer

IntroductionAlthough neoadjuvant chemo-radiotherapy (CRT) achieves low local recurrence rates in locally advanced rectal cancer (LARC), it raises a lot of concerns about long-term anal and sexual functions. We explored the efficacy of preoperative chemotherapy with mFOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, and irinotecan) in patients with LARC. Patients and MethodsPatients with LARC evaluated by pelvic magnetic resonance imaging (MRI) were enrolled in this trial. All received 4 to 6 cycles of mFOLFOXIRI. MRI was performed to assess clinical response after chemotherapy. Patients with mesorectal fascia-positive or ycT4a/b after re-evaluation would receive radiation before surgery, whereas responders would have immediate total mesorectal excision (TME). Adjuvant chemotherapy with mFOLFOX6 (folinic acid, 5-fluorouracil, and oxaliplatin) was recommended. The primary endpoint was the proportion of tumor downstaging to ypT0-2N0M0. The secondary endpoints were pathologic complete response rate (pCR), 3-year disease-free survival rate, and safety. ResultsOverall, 106 patients were enrolled and received neoadjuvant mFOLFOXIRI chemotherapy. A total of 103 participants underwent TME surgery. Among 103 patients who completed at least 4 cycles of preoperative chemotherapy, 2 received short-term radiation before TME, and 12 underwent long-term CRT after MRI evaluation. The pCR rate was 20.4%, and the tumor downstaging rate was 42.7%. Among patients without preoperative long-term radiotherapy, the pCR rate and tumor downstaging rate were 17.4% and 41.3%, respectively. Among the per-protocol population, the tumor downstaging rate was 48.1%, and the pCR rate was 20.3%. The chemotherapy-related toxicity was well-tolerated. ConclusionNeoadjuvant chemotherapy with mFOLFOXIRI and selective radiation does not seem to compromise outcomes in LARC. It could be a reasonable alternative to CRT in previously untreated patients with LARC.

A potential role for peripheral natural killer cell activity induced by preoperative chemotherapy in breast cancer patients.

Tumor-infiltrating lymphocytes are an important prognostic factor after neoadjuvant chemotherapy (NAC) in patients with breast cancer. Natural killer (NK) cells play critical roles in antitumor immune surveillance. Here, we assessed the relationship between peripheral natural killer (pNK) cell activity, tumor microenvironmental factors (TMEFs), and the therapeutic efficacy of preoperative chemotherapy in patients with breast cancer. In a cohort of 39 patients diagnosed with stage II-IV breast cancer who received NAC, we measured pNK cell activity by chromium release assay and assessed TMEF levels by next-generation sequencing. Following NAC, pNK cell activity was increased in 24/39 patients but decreased in 15/39 patients. Increased pNK cell activity following preoperative chemotherapy was associated significantly with the disappearance of axillary lymph node metastasis (Ax+; p = 0.0235). Increased pNK cell activity remained significantly associated with the disappearance of Ax+ in multivariate logistic regression analysis (OR 5.41, 95% CI 1.19-24.52, p = 0.0283). A Grade 2 or higher effect of NAC was associated with high pre-NAC cytotoxic T lymphocyte-associated protein 4 (CTLA-4) levels (p = 0.0281) and elevated post-NAC NK (p = 0.0005) cells and transforming growth factor-beta (TGF-β; p = 0.0350) levels. The disappearance of Ax+ was associated with high pre-NAC CTLA-4 levels (p = 0.0278) and elevated CD4 levels after NAC (p = 0.0250). The systemic activation of pNK cells after NAC may improve metastatic tumor elimination in patients with breast cancer owing to a release from local immunosuppression, and immune activation in the tumor microenvironment.

87O - mFOLFOXIRI versus mFOLFOX6 as neoadjuvant chemotherapy in locally advanced rectal cancer: A propensity score analysis from two prospective trials

Background: Neoadjuvant chemoradiotherapy (CRT) is the standard of treatment for locally advanced rectal cancer, but it delays administration of systemic chemotherapy, leading to high incidence of distant metastases. To enhance systemic chemotherapy and avoid the damage of radiation, full dose of neoadjuvant chemotherapy regimens with mFOLFOXIRI or mFOLFOX6 were both under investigation. Here, we aimed to compare the efficacy of preoperative chemotherapy with mFOLFOXIRI versus mFOLFOX6 in locally advanced rectal cancer. Methods: Prospectively maintained databases of patients from two clinical trials (NCT01211210 and NCT02217020) underwent preoperative treatment for locally advanced rectal cancer in a single center were included. Those had received mFOLFOXIRI or mFOLFOX6 chemotherapy alone preoperatively was selected for this study, including 90 patients with mFOLFOXIRI and 119 patients with mFOLFOX6. All patients had undergone total mesorectal excision. A comparative analysis was performed after the implementation of propensity score matching on the 2 main cohorts (mFOLFOXIRI and mFOLFOX6). Results: A total of 209 patients were enrolled in the study. After propensity score matching, 180 patients were selected. 90 patients were comparable in the two groups. Higher pathologic complete response rate was observed in mFOLFOXIRI group than that of mFOLFOX6 group (16.7% vs. 5.6%, p = 0.03). However, the tumor downstaging rate was comparable in this two group (41.1% vs. 37.8%, P = 0.76). The anal preservation rate was similar between the two groups (87.8% vs. 89.2%). But higher incidence of grade 3/4neutropenia (42.2% vs. 10%, P < 0.001) was shown in mFOLFOXIRI alone group than that of mFOLFOX6 group. Conclusions: Preoperative mFOLFOXIRI alone showed higher pCR rate than that of mFOLFOX6. The tumor downstaging rate was comparable between the two regimens. But the adverse events were more common in mFOLFOXIRI group. The intensive regimen might only fit for some highly selected patients. Whether the intensive regimen would improve the survival is unknown. Further follow-up is needed. Clinical trial identification: NCT01211210 and NCT02217020. Legal entity responsible for the study: Yanhong Deng. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

Safety and efficacy of preoperative chemotherapy followed by esophagectomy versus upfront surgery for resectable esophageal squamous cell carcinoma.

Neoadjuvant chemotherapy (NAC) followed by esophagectomy has become a standard treatment for esophageal squamous cancer (ESCC) in Japan. We used propensity-matching analysis to clarify the safety and efficacy of NAC in daily clinical practice. We reviewed the medical records of 335 patients with clinical Stage II/III ESCC diagnosed between 2007 and 2012, including 191 who received preoperative NAC (NAC group) and 144 treated by upfront surgery (US group). After propensity score matching, there were 118 patients in each group. We compared the postoperative complications and long-term outcomes between the groups. Seven patients in the NAC group underwent replacement therapy. Complications occurred in 76 (68.5%) and 76 (64.4%) patients in NAC and US groups, respectively (p = 0.51), and severe complications occurred in 17 (22.4%) and 30 (39.5%) patients, respectively (p = 0.057). One (0.8%) and three patients (2.5%) from the US group died within 30days and 90days after surgery, respectively, but none of the patients from the NAC group died within the same period. The 5-year survival rate was 54.9% in the NAC group and 41.2% in the US group (p = 0.024). NAC is a safe and effective treatment to improve prognosis in the clinical setting.

PS02.108: EFFECTS OF PREOPERATIVE CHEMOTHERAPY FOR ADVANCED ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Abstract Background In Japan, preoperative chemotherapy followed by surgery is the standard treatment for clinical stage II or III, excluding T4 thoracic esophageal squamous cell carcinoma (SCC). Here, we investigated the efficacy of preoperative chemotherapy in our hospital. Methods From January 2010 through December 2017, 33 patients with clinical stage II/III esophageal SCC underwent esophagectomy after preoperative chemotherapy with two cycles of cisplatin and 5-fluorouracil. Overall survival (OS) and clinical and pathological tumor responses were retrospectively evaluated. In addition, fluorodeoxyglucose (FDG) uptake was assessed by FDG-positron emission tomography/computed tomography (PET/CT). Results There were 9 patients with stage II and 24 with stage III esophageal SCC, and two cycles of chemotherapy were completed by 27 patients (81.8%). Three-year OS rates were 100% in patients with stage II and 66.7% in patients with stage III esophageal SCC, whose observation period exceeded beyond 3 years. Of the 33 patients who showed a clinical response at the primary site, 22 (66.7%) had a partial response (PR), and a 3-year OS of 85.7%, while 4 (12.1%) had a complete response (CR), and a 3-year OS of 100%. In regards to pathological response, as evaluated using The Japan Esophageal Society histological evaluation criteria, 3 patients (9.1%) were classified as grade 0, 18 (54.5%) as grade 1a, 4 (12.1%) as grade 1b, 6 (18.2%) as grade 2, and 2 (6.1%) as grade 3. Of the 22 patients who achieved PR, 14 (63.6%) were classified as either grade 0 or 1a. On the other hand, when we compared the maximum standardized uptake value (SUVmax) of FDG − PET/CT at the primary site before and after preoperative chemotherapy, the patients with high decreasing rates mostly belonged to the grade 1b-3 group. The OS rate tended to be higher in the grade 1b-3 group than in the grade 0–1a group. Conclusion Our present results suggest that, although pathological responses do not necessarily correspond to clinical tumor reduction, a good pathological response is potentially related to a better prognosis. Furthermore, the FDG uptake value may reflect pathological effects that occur owing to preoperative chemotherapy. Disclosure All authors have declared no conflicts of interest.