Pancreatic cancer remains a major troublesome clinical problem, with conventional cancer treatments having little impact on disease course. The extent of disease is often classified as localized, locally advanced, and metastatic. Radical operation is the most effective method, but only 15%-20% of patients have resectable disease, and around 20% of them survive to 5 years. For locally advanced, unresectable, and metastatic diseases, palliative treatment is more appropriate, but the median survival in these patients is less than 6 months and the 5-year survival rates are even lower than 4%. Neoadjuvant therapy has been gradually accepted in breast cancer and gastroenterological cancer, and its value in pancreatic cancer has attracted increasing interests. This paper reviews recent advances of neoadjuvant therapy in pancreatic cancer.
Adenocarcinoma ; therapy ; Chemotherapy, Adjuvant ; adverse effects ; methods ; Combined Modality Therapy ; Humans ; Neoadjuvant Therapy ; adverse effects ; methods ; Pancreatic Neoplasms ; therapy ; Radiotherapy, Adjuvant ; adverse effects ; methods

BACKGROUNDGastric cancer is one of the most common types of malignant tumors in China and East Asia and has the highest mortality rate of the malignant gastrointestinal tumors. Neoadjuvant chemotherapy is a systemic or local chemotherapy that is given prior to the local treatment of malignant tumors. Neoadjuvant therapy is currently showing some positive prospects; however, its clinical effects remain controversial. In this study, we used the modified FOLFOX7 (mFOLFOX7) regimen as a neoadjuvant chemotherapy regimen. Perioperative clinical and pathological efficacy, toxicity, effects of surgery, postoperative observation, and prognosis were studied to investigate its clinical efficacy and safety.

METHODSEighty patients with advanced gastric cancer were treated in our surgery department from 2005 to 2009; 38 of these patients received mFOLFOX7 neoadjuvant chemotherapy, the other 42 patients assigned to the control group. The perioperative effects of mFOLFOX7 chemotherapy, including clinical effects and toxicity, were observed in each patient.

RESULTSAfter mFOLFOX7 chemotherapy, clinical and pathologic stages decreased in 21.1% and 36.8% of the patients, respectively, but the results were not statistically significant (P = 0.129). The clinical response rate was 50% (19/38). Toxicity was mild; most adverse events were grade I or II and involved no severe infections or deaths. Compared with the control group, the radical resection rate increased (92.1% vs. 85.7%; P = 0.437); surgical effects were completed without an increased incidence of perioperative complications. The 1-, 2-, and 3-year survival rates were 78.70%, 57.40%, and 51.66%, respectively, in the neoadjuvant chemotherapy group and 78.57%, 56.87%, and 43.16%, respectively, in the control group.

CONCLUSIONSThe mFOLFOX7 regimen was very effective and well-tolerated as a neoadjuvant chemotherapy for advanced gastric cancer. However, the 1-, 2-, and 3-year survival rates in the mFOLFOX7 group were not significantly different from the control group.

Adult ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Female ; Fluorouracil ; adverse effects ; therapeutic use ; Humans ; Leucovorin ; adverse effects ; therapeutic use ; Male ; Middle Aged ; Neoadjuvant Therapy ; adverse effects ; methods ; Organoplatinum Compounds ; adverse effects ; therapeutic use ; Stomach Neoplasms ; drug therapy ; surgery

OBJECTIVES: Neoadjuvant chemotherapy combined with radical surgery has become the treatment model for locally advanced rectal cancer. The purpose of this study was to evaluate the safety and efficacy of postoperative mFOLFOX6 regimen chemotherapy for locally resectable advanced rectal cancer. METHODS: This was a prospective study. A total of 82 patients with locally advanced rectal cancer admitted to Affiliated Nanhua Hospital, University of South China from February 2015 to December 2017 were selected as the subjects. The patients received 4 courses of mFOLFOX6 chemotherapy and underwent surgery within 4-6 weeks after chemotherapy. The incidences of chemotherapy-related adverse reactions, postoperative complications, and clinical pathological reactions were analyzed. RESULTS: In the period from mFOLFOX6 chemotherapy to preoperative, 82 patients with locally advanced rectal cancer was reported chemotherapy-related adverse reactions, including Grade 4 neutropenia (2.4%), catheter related infection (2.4%), and anorexia (2.4%), Grade 3 nausea (2.4%) and anorexia (2.4%), Grade 2 neutropenia (14.6%) and peripheral neuropathy (7.3%). Finally, 76 patients with locally advanced rectal cancer completed surgery, including 56 (73.7%) with anterior rectum resection, 16 (21.1%) with abdominal perineal resection, and 72 (94.7%) with pelvic nerve preservation. A total of 22 (28.9%) patients had surgical complications, including 8 (10.5%) with complications of Grade 3 or above. The complications with high incidence were intestinal obstruction, anastomotic leakage, and sepsis. Among the 76 patients who completed chemotherapy and surgery, T stage was decreased in 28 (36.8%) and N stage was decreased in 44 (57.9%); forty-two (55.3%) were in pathological Stage I, 20 (26.3%) in Stage IIA, 12 (15.8%) in Stage IIB, and 2 (2.6%) in Stage IIIA. Ten patients were suspected of tumor invasion of surrounding organs before chemotherapy, of which 4 patients did not need to extend the resection of surrounding organs after chemotherapy and achieved R0 resection of tumor; 2 in T CONCLUSIONS Preoperative mFOLFOX6 regimen chemotherapy for locally resectable advanced rectal cancer is a safe and feasible treatment strategy, and it is worthy of clinical application.
Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; China ; Fluorouracil/adverse effects* ; Humans ; Neoadjuvant Therapy ; Neoplasm Staging ; Prospective Studies ; Rectal Neoplasms/surgery* ; Treatment Outcome

OBJECTIVETo investigate the efficacy and safety of S-1 combined with oxaliplatin (SOX regimen) as neoadjuvant chemotherapy for advanced gastric cancer.

METHODSFrom November 2009 to September 2010, 66 patients with advanced gastric cancer were enrolled in this study. Thirty-two patients were given preoperative chemotherapy using SOX regimen. S-1 was administered orally 80 mg·(m(2))(-1)·d(-1) for 14 days, while oxaliplatin(130 mg/m(2)) was administered intravenously on day 1. The treatment was repeated every 3 weeks. The efficacy and safety were assessed every 2 cycles of chemotherapy. The other 34 patients were in control group. R0 resection rate and D2 lymph nodes dissection rate were analyzed for all surgical patients.

RESULTSThe overall response rate of neoadjuvant chemotherapy was 68.8% and disease control rate was 93.8%. Grade 3/4 hematological toxicities were liver dysfunction(9.4%), anemia(6.3%) and neutropenia(6.3%), and non-hematological toxicities included vomiting(12.5%) and anorexia(5.7%). Thirty-two patients after neoadjuvant chemotherapy underwent surgical resection, of whom 25 patients(78.1%) received D2 lymph nodes dissection and the R0 resection rate was 81.3%,higher than those in control group(D2 lymph nodes dissection rate:67.6%,P =0.028; R0 resection rate:73.5%,P =0.040).

CONCLUSIONSOX regimen as neoadjuvant chemotherapy is associated with high efficacy, acceptable adverse effect, and increased rate of D2 lymph nodes dissection and R0 resection.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Chemotherapy, Adjuvant ; Female ; Fluorouracil ; administration & dosage ; adverse effects ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy ; Organoplatinum Compounds ; administration & dosage ; adverse effects ; Stomach Neoplasms ; drug therapy ; Treatment Outcome ; Young Adult

OBJECTIVETo explore efficacy of neoadjuvant radiochemotherapy in locally advanced low rectal cancer.

METHODSFrom May 2001 to August 2005, 105 patients with locally advanced low rectal cancer (T3, T4) were treated by preoperative radiotherapy to pelvis, 2.0 Gy daily up to 40-46 Gy in 4-5 weeks concomitantly with oral capecitabine at 1250 mg x m(-2) x d(-1) for 10 weeks up to surgery. In all patients surgery was carried out under the rule of total mesorectal excision technique.

RESULTSAll patients finished the course of neoadjuvant radiochemotherapy. Among them, 36 patients experienced adverse effects. Thirteen patients resulted in complete tumor response and spared the operation. Ninety-two patients were operated on with radical resection, among them 71 patients with low anterior resection, 17 with Parks' colo-anal anastomosis and 4 with abdomino-perineal resection, so sphincter preservation was achieved in 96.2%. In postoperative pathological studies, 11 cases showed complete tumor regression. According to the TNM staging system, 24 cases were ranged T0N0, and 23 cases T2N0, 43 cases T3N0, 2 cases T4N0, 5 cases T2N1, 8 cases T3N1; and according to Dworak's tumor regression grading, 5 cases were ranked TGR0, and 18 cases TGR1, 11 cases TGR2, 47 cases TGR3, 24 cases TGR4. Pathologic downstaging was achieved in 78.1%, including complete response (TGR4) and intermediate response (TGR2 + 3). No operative death occurred. Anastomotic leakage was found in 5 cases, including 3 rectovaginal fistula. All patients have been followed up for 16-67 months, and lung metastasis occurred in 4 cases, liver metastasis in 2 patients and local recurrence in 4 patients. Three patients died of distant metastasis. The 3-year disease-free survival was 82.8% and overall survival was 96.5%.

CONCLUSIONSNeoadjuvant radiochemotherapy brings tumor down-staging and increases resectability and sphincter preservation, decreases recurrence and improves survival in locally advanced low rectal cancer.

Chemotherapy, Adjuvant ; adverse effects ; methods ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Neoadjuvant Therapy ; adverse effects ; methods ; Preoperative Care ; methods ; Radiotherapy, Adjuvant ; adverse effects ; methods ; Rectal Neoplasms ; mortality ; surgery ; therapy ; Survival Rate ; Treatment Outcome

BACKGROUND/AIMS: In gastric cancer, the rate of recurrence and metastasis following radical resection is high, necessitating improvement in survival and cure rates. Neoadjuvant chemotherapy (NAC) has potential benefits for locally advanced gastric cancer; however, the surgical benefits and effects on survival are unclear. This study evaluates the effectiveness of NAC in locally advanced gastric cancer and compares clinical outcomes of doublet and triplet regimens. METHODS: We reviewed patient medical records of 383 patients who underwent NAC (n=41) or surgery only (n=342) for treatment of locally advanced gastric cancer. The baseline characteristics and clinical outcomes were compared between the groups. Chemotherapy patients were classified according to regimen, doublet (n=28) and triplet (n=13), and NAC-related clinical response, safety, and toxicity were analyzed. RESULTS: The baseline characteristics did not differ significantly between groups. After NAC, the tumor downstage rate was 51.2% (21/41); however, overall survival (p=0.205) and disease-free survival (p=0.415) were not significantly different between the groups. On subgroup analysis, no significant differences in drug toxicity (p=0.604) or clinical response (p=0.374) were found between outcomes of doublet and triplet chemotherapy regimens. CONCLUSIONS: In patients with locally advanced gastric cancer, NAC showed tolerable drug toxicity and increased tumor downstage, but NAC failed to increase the survival rate, which may be caused by a high D2-lymphadenectomy rate. Therefore, NAC was found to be a therapeutic option for select gastric cancer patients.
Adenocarcinoma ; Disease-Free Survival ; Drug Therapy* ; Drug-Related Side Effects and Adverse Reactions ; Humans ; Medical Records ; Neoadjuvant Therapy ; Neoplasm Metastasis ; Recurrence ; Stomach ; Stomach Neoplasms* ; Survival Rate ; Triplets*

OBJECTIVETo analyze the clinical features and risk factors of anastomotic leakage after radical esophagectomy of esophageal carcinoma.

METHODSThe clinical data of 547 esophageal cancer patients underwent radical esophagectomy in Tianjin Medical University Cancer Hospital from January 2012 to December 2013 was analyzed retrospectively. There were 421 male and 126 female patients, with a median age of 65 years (ranging from 29 to 82 years). There were 155 cases of upper esophageal carcinoma, 340 cases of middle esophageal carcinoma and 52 cases of lower esophageal carcinoma. The surgical procedures included 41 cases completed through Sweet, 145 cases completed through McKeown, 279 cases completed through Ivor Lewis, 82 cases completed through minimally invasive esophagectomy. Moreover, 24 of 547 cases underwent preoperative neoadjuvant radiochemotherapy. χ² test and Cox's proportional hazards regression model were used for univariate analysis and multivariate analysis of the risk factors of postoperative anastomotic leakage.

RESULTSTwenty-seven of 547 cases with esophagectomy occurred anastomotic leakage and the incidence rate was 4.94% (27/547). One of 27 cases died and the mortality rate was 3.70% (1/27). The time of anastomotic leakage found was 4 to 45 days, with a median time of 10 days. There were 0 case of early leakage, 20 cases of mid-term leakage, 7 cases of late leakage. Three of 27 cases with anastomotic leakage had tracheoesophageal fistula, while 3 cases had contralateral pleural fistula. As to the incidence rate of anastomotic leakage, there was statistically significant difference between cervical anastomotic leakage (8.14%, 18/221) and intrathoracic anastomotic leakage (2.76%, 9/326) (χ² =7.41, P=0.000), among Sweet (4.88%, 2/41), McKeown (9.66%, 14/145), Ivor Lewis (2.51%, 7/279) and MIE (4.88%, 4/82) (χ² =21.48, P=0.000), and between with (16.67%, 4/24) and without (4.40%, 23/523) neoadjuvant radiochemotherapy (χ² =9.20, P=0.000). The multivariate analysis showed that anastomotic site (HR=2.594, P=0.048), surgical approach (HR=5.689, P=0.003) and preoperative neoadjuvant radiochemotherapy (HR=3.604, P=0.027) are independent risk factors for anastomotic leakage after esophagectomy.

CONCLUSIONSThe mid-term anastomotic leakage after esophagectomy occurs higher. McKeown is a main surgical procedure and neoadjuvant radiochemotherapy is an important factor for the anastomotic leakage.

Adult ; Aged ; Aged, 80 and over ; Anastomotic Leak ; Carcinoma ; surgery ; Chemoradiotherapy ; Esophageal Neoplasms ; surgery ; therapy ; Esophagectomy ; adverse effects ; Female ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy ; Retrospective Studies ; Risk Factors

To evaluate the efficacy and safety of neoadjuvant chemotherapy combined with bevacizumab versus neoadjuvant chemotherapy alone for Her2-negative breast cancer.We searched PubMed, the Cochrane Library, Web of Science, CNKI, Wanfang Database and the abstracts of major international conferences in recent 5 years to identify prospective randomized controlled clinical trials that met the inclusion and exclusion criteria. Study selection and analyses were undertaken according to the Cochrane Handbook. Meta-analysis was performed using RevMan 5.3 software.Six trials were identified with 4440 eligible patients. The results of this meta-analysis showed that the rate of pathological complete response (pCR) was higher in Her-2 negative breast cancer patients receiving bevacizumab combined with neoadjuvant chemotherapy than that in patients with neoadjuvant chemotherapy alone (24.7% vs 20.1%,=1.23, 95%:1.10-1.37,<0.01). In addition, the pCR rate rose up when bevacizumab was added to neoadjuvant chemotherapy both in hormone receptor-positive patients (13.1% vs 10.2%,=1.28, 95%:1.04-1.58,<0.05) and in hormone receptor-negative patients (46.3% vs 37.1%,=1.25, 95%:1.12-1.39,<0.01). Statistical differences were observed in the rate of relevant adverse events such as hypertention (3.2% vs 0.6%,=5.292, 95%:2.933-9.549,<0.01) and mucositis (10.5% vs 2.0%,=5.340, 95%:3.743-7.617,<0.01) between the combination group and the chemotherapy alone group. Differences in other toxicities such as febrile neutropenia, infection, surgical complications, neutropenia and hand-foot syndrome were also found to be statistically significant between the combination group and the chemotherapy alone group (all<0.05), while such difference was not found in the occurrence of peripheral neuropathy (>0.05).The addition of bevacizumab to neoadjuvant chemotherapy in Her2-negative breast cancer can significantly improve pathological complete response, but may bring more grade 3 and 4 toxicities.More neoadjuvant trials need to be done to define subgroups of Her2-negative breast cancer that would have clinically significant long-term benefit from bevacizumab treatment.
Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; toxicity ; Bevacizumab ; adverse effects ; therapeutic use ; toxicity ; Breast Neoplasms ; chemistry ; drug therapy ; Female ; Humans ; Neoadjuvant Therapy ; adverse effects ; methods ; Prospective Studies ; Receptor, ErbB-2 ; analysis ; Triple Negative Breast Neoplasms ; drug therapy

Objective: To evaluate the efficacy and survival outcomes of dose-dense (biweekly) carboplatin plus paclitaxel (PC) as neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC), and to explore an optimal neoadjuvant chemotherapy regimen for TNBC. Methods: Patients diagnosed as TNBC(cT1-4N0-3M0) in Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College Between January 2008 and September 2018 who received dose-dense PC and standard 3-weekly PC as NAC were 1∶1 matched using propensity score matching (PSM) to compare the efficacy, safety and survival outcomes. Results: One hundred of TNBC patients were enrolled (50 patients were divided in dose-dense group, 50 patients in standard group). The objective response rate (ORR) of dose-dense group and standard group were both 90.0% (45/50). The grade 3-4 neutropenia in dose-dense group was less than that of standard group (32.7% vs. 68.0%, P=0.001), while the rate of ALT/AST elevation in dose-dense group was higher than that of standard group (57.1% vs. 32.0%, P=0.012). The pathological complete response (pCR) rates were 34.0% (17/50) in dose-dense group and 38.0% (19/50) in standard group, without statistically significance (P=0.677). The median follow-up time was 55 months (3-150 months). The 5-year recurrence-free survival (RFS) in dose-dense group and standard group were 83.5% and 75.2%, respectively the 5-year overall survival (OS) in dose-dense and standard group were 87.9% and 84.5% the difference were not statistically significant (P=0.322 and 0.647, respectively). Patients with residual disease (tumor size≥1 cm or lymph node positive) had poor prognosis, the 5-year RFS and OS were 59.3% and 68.5%, respectively. Conclusions: Dose-dense PC has similar efficacy with standard 3-weekly PC and has a good safety profile. Since dose-dense regimen can shorten the duration of therapy, it can be an alternative in TNBC.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carboplatin/therapeutic use* ; Humans ; Neoadjuvant Therapy/adverse effects* ; Paclitaxel/therapeutic use* ; Treatment Outcome ; Triple Negative Breast Neoplasms/pathology*

Objective: To investigate postoperative complications of patients undergoing neoadjuvant therapy followed by radical gastrectomy, and to analyze their influence on the prognosis. Methods: A retrospective case-control study was used. Case inclusion criteria: (1) gastric adenocarcinoma confirmed by histopathology; (2) preoperative imaging examination showed no distant metastasis or peritoneal dissemination; (3) undergoing radical gastrectomy and D2 lymph node dissection after neoadjuvant therapy; (4) complete clinicopathological and follow-up data. According to the above criteria, clinical data of 490 gastric cancer patients who underwent radical gastrectomy in the Cancer Hospital of Chinese Academy of Medical Sciences, Peking Union Medical College from January 2008 to December 2018 were retrospectively collected, including 358 males and 132 females with mean age of (55.0±10.6) years. Neoadjuvant chemotherapy regimens included SOX (S-1+ oxaliplatin, n=151), XELOX (capecitabine+oxaliplatin, n=155), FLOT (docetaxel+oxaliplatin+fluorouracil, n=66), and DOS (docetaxel+ oxaliplatin+S-1, n=68). Preoperative concurrent chemoradiotherapy was performed in 100 patients. SOX regimen was used for 2-4 cycles as induction chemotherapy plus concurrent chemoradiotherapy (3D IMRT+S-1). Postoperative complications were defined as surgery-related complications, mainly including hemorrhage, anastomotic leakage, obstruction, anastomotic stenosis, pulmonary infection, abdominal infection, etc. Postoperative complications were graded according to Clavien-Dindo classification. Log-rank test and Cox regression model were used for univanriate multivariate prognostic analysis, respectively. Results: A total of 101 complications ocaured after operation in 87 (17.8%) patients, including 29 cases of major complications (Clavien-Dindo III to V), and 58 cases of minor complications (Clavien-Dindo I to II). Multivariate analysis showed that age > 65 years (HR=3.077, 95% CI: 1.827-5.184, P<0.001) and total gastrectomy (HR=1.735, 95% CI: 1.069-2.814, P=0.026) were independent risk factors for postoperative complications in patients with gastric cancer undergoing neoadjuvant therapy and radical gastrectomy (both P<0.05). The follow-up period was 0.7 to 131.8 months (median 21.5 months), and the 5-year overall survival rate was 47.4%. The 5-year overall survival rates of the complication group (87 cases) and the non-complication group (403 cases) were 33.2% and 50.9%, respectively (P=0.001). Multivariate analysis showed that age (HR=1.906, 95% CI: 1.248-2.913, P=0.003), ypTNM II to III stage (II stage: HR=5.853, 95% CI: 1.778-19.260, P=0.004; III stage: HR=10.800, 95% CI: 3.411-34.189, P<0.001), surgery time>3.5 h (HR=1.492, 95% CI: 1.095-2.033, P=0.011), total gastrectomy (HR=1.657, 95% CI: 1.216-2.257, P=0.001) and postoperative complications (HR=1.614, 95% CI: 1.125-2.315, P=0.009) were independent risk factors for prognosis, and postoperative adjuvant therapy (HR=0.578, 95% CI: 0.421-0.794, P=0.001) was an independent protective factor for prognosis. Conclusions: The occurrence of postoperative complications in gastric cancer patients undergoing neoadjuvant therapy is closely related to the age of the patients and the range of surgical resection. It is beneficial to improve the prognosis for these patients by paying more attention to the prevention of postoperative complications and the reinforcement of postoperative adjuvant therapy.
Adenocarcinoma/surgery* ; Adult ; Aged ; Female ; Gastrectomy/adverse effects* ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/surgery*