Impact Of Postoperative Adjuvant Chemotherapy Research Articles

Postoperative Chemotherapy for Thoracic Pathological T3N0M0 Esophageal Squamous Cell Carcinoma.

The role of postoperative chemotherapy (POCT) in pathologic T3N0M0 thoracic esophageal squamous cell carcinoma (TESCC) has not been well addressed. The purpose of this study was to investigate the impact of postoperative adjuvant chemotherapy on survival, recurrence, and toxicities in pathologic T3N0M0 TESCC. This study included 582 patients with pT3N0M0 TESCC who were treated at Sichuan Cancer Hospital from January 2009 to December 2017. The patients were divided into two groups: surgery plus postoperative chemotherapy group (S + POCT), and surgery group (S group). Propensity score matching was used to create patient groups that were balanced across several covariates (n = 236 in each group). Outcome measures included overall survival (OS) and disease-free survival (DFS). After PSM, both groups have balance factors. S + POCT have significantly improved the 5-year OS and DFS (OS, 70.8% vs. 52.8%, p <0.0001; DFS, 66.5% vs. 50.2%, p < 0.0001). Multivariate Cox analyses in the matched samples revealed that S + POCT were independently associated with longer OS (hazard ratio (HR) = 0.56, 95% confidence index (CI) 0.41-0.77, p < 0.0001) and longer DFS (HR = 0.60, 95% CI 0.45-0.82, p = 0.001) than surgery alone. Subgroup analyses showed that prognostic effect of POCT was significantly influenced by the number of resected lymph node (≤ 20) and pStage IIB but not influenced by the number of node > 20 and pStage IIA. Postoperative adjuvant chemotherapy is strongly associated with improved OS and DFS in patients with pT3N0M0 TESCC. A multicenter, randomized, phase III clinical trial is warranted to confirm these findings.

Clinicopathological features and impact of adjuvant chemotherapy on the long-term survival of patients with multiple gastric cancers: a propensity score matching analysis

BackgroundLittle is known about the correlation between the clinicopathological features, postoperative treatment, and prognosis of multiple gastric cancers (MGCs). In this study, we aimed to investigate the correlation between these features and the impact of postoperative adjuvant chemotherapy on the long-term survival of patients with MGC.MethodsThe clinical and pathological data of patients diagnosed with gastric adenocarcinoma who had radical gastrectomy from January 2007 to December 2016 were analyzed. Using propensity score matching, the prognostic differences, and the impact of postoperative adjuvant chemotherapy between those with MGC and solitary gastric cancers (SGC) were compared.ResultsAmong the 4107 patients investigated, the incidence of MGC was 3.2% (133/4107). Before matching, patients with MGC and SGC had disparities in the type of gastrectomy, pathological tumor stage (pT), pathological node stage (pN), and pathological tumor-node-metastasis stage (pTNM). After a 1:4 ratio matching, the clinical data of 133 cases of MGC and 532 cases of SGC were found to be comparable. The 5-year overall survival (OS) rate was 56.6% in the entire matched cohort, 48.1% in the MGC group, and 58.7% in the SGC group (P = 0.013). Multivariate analysis revealed that MGC, age, pT stage, pN stage, and adjuvant chemotherapy were independent predictors of OS (all P < 0.05). Stratified analyses demonstrated that for the cohort of advanced gastric cancer (AGC) patients who did not had adjuvant chemotherapy, the 5-year OS rate of advanced cases of MGC was inferior than that of SGC patients (34.0% vs. 46.1%, respectively; P = 0.025) but there were no significant difference in the 5-year OS rate between advanced MGC and SGC patients who had adjuvant chemotherapy (48.0% vs. 53.3%, respectively; P = 0.292). Further, we found that the 5-year OS rate of advanced MGC who had adjuvant chemotherapy was significantly higher than those who did not had adjuvant chemotherapy (48.0% vs. 34.0%, P = 0.026).ConclusionsPatients with advanced MGC was identified as having a poorer survival as to SGC patients, but the implementation of postoperative adjuvant chemotherapy showed that it had the potential to significantly improve the long-term prognoses of MGC patients.

Impact of Postoperative Adjuvant Chemotherapy Following Long-course Chemoradiotherapy in Stage II Rectal Cancer.

Use of adjuvant chemotherapy (AC) following neoadjuvant chemoradiation (nCRT) is controversial in rectal cancer (RC). We assessed a multi-institutional database to determine if there was benefit from AC for pathologic stage II RC patients and whether the addition of oxaliplatin to fluoropyrimidine (OXAC) therapy impacted outcomes. We included patients who underwent nCRT and had pathologic stage II (ypT3/4 ypN0) tumors. Disease-free survival and overall survival were assessed. Multivariate Cox models adjusting for age, sex, Eastern Cooperative Oncology Group, high-risk features (pT4, poor differentiation, <12 nodes removed, lymphovascular/perineural invasion, or obstruction/perforation), and clinical stage were constructed. Of 485 patients, 73.6% received AC, of which 25.5% received OXAC. Patients receiving AC were younger (median age 61 vs. 64; P=0.003) and had higher rates of total mesorectal excision (81.5% vs. 78.9%; P=0.049), but had similar high-risk features, performance status, clinical stage, margin status, preoperative carcinoembryonic antigen, and nCRT regimen. In univariate analysis, overall survival was improved with fluoropyrimidine AC compared with no AC or OXAC (P=0.049), but not disease-free survival (P=0.33). In multivariate analysis, any AC, fluoropyrimidine AC, or OXAC did not improve outcomes. After stratifying patients by the presence of high-risk features, elevated carcinoembryonic antigen, margin status, or preoperative clinical stage, we did not identify a group with improved outcomes following AC. In this multi-institutional cohort of yp stage II RC patients, we failed to identify a group that derives benefit from AC following nCRT. The addition of oxaliplatin did not appear to improve outcomes when compared with fluoropyrimidine alone.

The impact of postoperative adjuvant chemotherapy on the development of nonalcoholic fatty liver disease after pancreatoduodenectomy

BackgroundNonalcoholic fatty liver disease (NAFLD) after pancreatoduodenectomy (PD) is increasingly being recognized as a late postoperative complication, but the main causes have not been fully investigated. This study aimed to clarify the relationship between NAFLD after PD and postoperative adjuvant chemotherapy, focusing particularly on the adjuvant chemotherapy regimens administered. Materials and methodsWe retrospectively reviewed the medical records of 154 patients who underwent PD from April 2007 to December 2013, to identify the clinicopathologic factors most strongly influencing NAFLD development after PD. Moreover, the postoperative adjuvant chemotherapeutic regimen and the course after the cessation of adjuvant chemotherapy were examined in detail. ResultsThe incidence of postoperative NAFLD was 26.6% (41/154). The incidence of NAFLD was significantly higher in the patients with than in those without adjuvant chemotherapy: 38% versus 19% (P = 0.016). Multivariate analysis identified postoperative adjuvant chemotherapy (P = 0.021) and remnant pancreatic volume (P < 0.0001) as independent risk factors. The prevalence of NAFLD after PD was higher in patients treated with the S-1 regimen than in those given either regimens such as those containing gemcitabine or no adjuvant chemotherapy. Recovery from NAFLD 1 y after the cessation of adjuvant chemotherapy was observed in 54.5% (12/22) of patients receiving this treatment. In those treated with the S-1 regimen, improvement was more frequent than in those not receiving adjuvant chemotherapy (57.1% versus 11.8%, P = 0.018). ConclusionsConsidering the development of NAFLD, adjuvant chemotherapy after PD should be cared for the patients with small remnant pancreas.

Future of therapy for rectal cancer.

Since 2004, the standard of care for patients with cT3 and/or N+ rectal cancer has been preoperative chemoradiation followed by surgery and postoperative adjuvant chemotherapy. A number of advances have occurred and are defining the future of rectal cancer therapy. Among these are short course radiation, the impact of postoperative adjuvant chemotherapy, selective radiation and selective surgery, and new chemoradiation regimens with novel agents. This review will examine these developments and assess their impact on the future therapy of rectal cancer.

Postoperative adjuvant chemotherapy in rectal cancer operated for cure.

Colorectal cancer is one of the most common types of cancer in the Western world. Apart from surgery - which remains the mainstay of treatment for resectable primary tumours - postoperative (i.e., adjuvant) chemotherapy with 5-fluorouracil (5-FU) based regimens is now the standard treatment in Dukes' C (TNM stage III) colon tumours i.e. tumours with metastases in the regional lymph nodes but no distant metastases. In contrast, the evidence for recommendations of adjuvant therapy in rectal cancer is sparse. In Europe it is generally acknowledged that locally advanced rectal tumours receive preoperative (i.e., neoadjuvant) downstaging by radiotherapy (or chemoradiotion), whereas in the US postoperative chemoradiotion is considered the treatment of choice in all Dukes' C rectal cancers. Overall, no universal consensus exists on the adjuvant treatment of surgically resectable rectal carcinoma; moreover, no formal systematic review and meta-analysis has been so far performed on this subject. We undertook a systematic review of the scientific literature from 1975 until March 2011 in order to quantitatively summarize the available evidence regarding the impact of postoperative adjuvant chemotherapy on the survival of patients with surgically resectable rectal cancer. The outcomes of interest were overall survival (OS) and disease-free survival (DFS). CCCG standard search strategy in defined databases with the following supplementary search. 1. Rect* or colorect* - 2. Cancer or carcinom* or adenocarc* or neoplasm* or tumour - 3. Adjuv* - 4. Chemother* - 5. Postoper* Randomised controlled trials (RCT) comparing patients undergoing surgery for rectal cancer who received no adjuvant chemotherapy with those receiving any postoperative chemotherapy regimen. Two authors extracted data and a third author performed an independent search for verification. The main outcome measure was the hazard ratio (HR) between the risk of event between the treatment arm (adjuvant chemotherapy) and the control arm (no adjuvant chemotherapy). The survival data were either entered directly in RevMan or extrapolated from Kaplan-Meier plots and then entered in RevMan. Due to expected clinical heterogeneity a random effects model was used for creating the pooled estimates of treatment efficacy. A total of 21 eligible RCTs were identified and used for meta-analysis purposes. Overall, 16,215 patients with colorectal cancer were enrolled, 9,785 being affected with rectal carcinoma. Considering patients with rectal cancer only, 4,854 cases were randomized to receive potentially curative surgery of the primary tumour plus adjuvant chemotherapy and 4,367 to receive surgery plus observation. The mean number of patients enrolled was 466 (range: 54-1,243 cases). 11 RCTs had been performed in Western countries and 10 in Japan. All trials used fluoropyrimidine-based chemotherapy (no modern drugs - such as oxaliplatin, irinotecan or biological agents - were tested).Overall survival (OS) data were available in 21 RCTs and the data available for meta-analysis regarded 9,221 patients: of these, 4854 patients were randomized to adjuvant chemotherapy (treatment arm) and 4,367 patients did not receive adjuvant chemotherapy (control arm). The meta-analysis of these RCTs showed a significant reduction in the risk of death (17%) among patients undergoing postoperative chemotherapy as compared to those undergoing observation (HR=0.83, CI: 0.76-0.91). Between-study heterogeneity was moderate (I-squared=30%) but significant (P=0.09) at the 10% alpha level.Disease-free survival (DFS) data were reported in 20 RCTs, and the data suitable for meta-analysis included 8,530 patients. Of these, 4,515 patients were randomized to postoperative chemotherapy (treatment arm) and 4,015 patients received no postoperative chemotherapy (control arm). The meta-analysis of these RCTs showed a reduction in the risk of disease recurrence (25%) among patients undergoing adjuvant chemotherapy as compared to those undergoing observation (HR=0.75, CI: 0.68-0.83). Between-study heterogeneity was moderate (I-squared=41%) but significant (P=0.03).While analyzing both OS and DFS data, sensitivity analyses did not find any difference in treatment effect based on trial sample size or geographical region (Western vs Japanese). Available data were insufficient to investigate on the effect of adjuvant chemotherapy separately in different TNM stages in terms of both OS and DFS. No plausible source of heterogeneity was formally identified, although variability in treatment regimens and TNM stages of enrolled patients might have played a significant role in the difference of reported results. The results of this meta-analysis support the use of 5-FU based postoperative adjuvant chemotherapy for patients undergoing apparently radical surgery for non-metastatic rectal carcinoma. Available data do not allow us to define whether the efficacy of this treatment is highest in one specific TNM stage. The implementation of modern anti-cancer agents in the adjuvant setting is warranted to improve the results shown by this meta-analysis. Randomized trials of adjuvant chemotherapy for patients receiving preoperative neoadjuvant therapy are also needed in order to define the role of postoperative chemotherapy in the multimodal treatment of resectable rectal cancer.

Postoperative adjuvant therapy for completely resected early-stage non-small cell lung cancer

Consensus on adjuvant therapy for completely resected non-small cell lung cancer until 2002 was as follows. (1) There was no significant impact of postoperative adjuvant chemotherapy based on meta-analysis and previous clinical trials. (2) Confirmatory studies are necessary in large-scale prospective clinical trials. However, recent mega trials have introduced epoch-making changes for postoperative adjuvant chemotherapy in clinical practice since ASCO 2003. The effectiveness of UFT in N0 patients was confirmed. Patients with completely resected stage I non-small cell lung cancer, especially T2N0 adenocarcinoma, will benefit from adjuvant chemotherapy with UFT. The results of the International Adjuvant Lung Trial (IALT) have confirmed the meta-analysis in 1995. Also, both the JBR10 and Cancer and Leukemia Group B (CALGB) 9633 studies have also confirmed positive IALT results of the benefit for postoperative platinum-based chemotherapy in completely resected non-small cell lung cancer. Adjuvant chemotherapy for pathological stage IB to II, completely resected non-small cell lung cancer is standard care based on clinical trials. UFT showed the strongest evidence for IB in Japan. Platinum doublet chemotherapy with third-generation anticancer agents is also recommended. Adjuvant chemotherapy should be offered as standard care to patients after completely resected early stage non-small cell lung cancer. However, there is no evidence of the feasibility and efficacy for adjuvant chemotherapy with the platinum-based regimen in Japan. Careful management should be necessary in such treatment.

Is postoperative adjuvant chemotherapy necessary in locally advanced rectal cancers after preoperative chemoradiation

To evaluate the impact of postoperative adjuvant chemotherapy in patients with locally advanced rectal cancers who have received preoperative chemoradiation, and to determine which post-chemoradiation TNM stages will benefit from postoperative chemotherapy. Between 1986 and 2000, 209 patients with tethered or fixed rectal cancers were treated with preoperative chemoradiation according to 3 different schedules. In schedule I, 54 patients were treated with 40 Gy RT plus concurrent 5FU infusion and mitomycin C. In schedule II, 27 patients were treated with “sandwich” chemoradiation: 40 Gy preoperative RT with concurrent 5FU infusion, leucovorin and mitomycin C, and 18 Gy postoperative RT with similar concurrent chemotherapy. The design of both schedules I and II did not include any postoperative adjuvant chemotherapy. In schedule III, 128 patients were treated with 50 Gy preoperative RT concurrent with 5FU infusion, leucovorin and mitomycin C, followed by 5 cycles of postoperative bolus 5FU/leucovorin chemotherapy. After excluding patients with M1 disease and patients in schedules I and II who have received some postoperative chemotherapy off-protocol, 184 patients were available for the analysis. There were 134 males and 50 females. The median age was 62 years (range: 30–82 years). There were 141 tethered and 43 fixed rectal cancers. There were 91 low- (3–5 cm from the anus), 82 mid- (6–10 cm) and 11 high- (> 10 cm) rectal cancers. 97 patients had an abdominoperineal resection, 84 patients had an anterior resection, 2 patients had a Hartman’s resection and one patient had an exenteration. The post-chemoradiation TNM stage distribution was as follow: 36 stage 0 (T0N0M0), 52 stage I, 58 stage II, and 38 stage III. 99 patients (in schedule III) received postoperative bolus 5FU/leucovorin chemotherapy and 85 patients did not. 65% (55/88) of stages 0 and I, and 46% (44/96) of stages II and III had received postoperative adjuvant chemotherapy. As of January 1, 2004, 100 patients are alive, 78 patients were dead and 6 patients were lost to follow-up. 120 patients (65%) were free of relapse, 9 patients (5%) had local recurrence alone, 44 patients (24%) had distant metastases, and 11 patients (6%) had both local and distant failures. The 5-year overall survival was 65% for all 184 patients, 77% for those who received postoperative chemotherapy versus 52% for those who did not (logrank p = 0.0001). The 5-year relapse-free survival was 65%, 76% for the chemotherapy group and 57% for the no-chemotherapy group (p = 0.00017). The 5-year actuarial distant failure rate was 23% for those who received postoperative chemotherapy and 42% for those who did not. For stages 0-I, the 5-year overall survival was 85% for the chemotherapy group and 78% for the no-chemotherapy group (p = 0.34), and the 5-year relapse-free survival was 87% for the chemotherapy group and 77% for the no-chemotherapy group (p = 0.18). For stages II and III, there were statistically significant differences in the outcome with the addition of postoperative chemotherapy. The 5-year overall survival was 66% for those who received chemotherapy and 37% for those who did not (p = 0.00079), and the respective 5-year relapse-free survival was 62% versus 35% (p = 0.0033). The 5-year actuarial distant failure rate was 38% for the chemotherapy group and 58% for the no-chemotherapy group (p = 0.02). In the multivariate analysis of prognostic factors (post-chemoradiation stage, postoperative bolus chemotherapy, fixed versus tethered tumors, different treatment schedules, lymphovascular/ perineural invasion, pT4 and positive nodal disease), postoperative chemotherapy was an independent prognosticator for the relapse-free survival (hazard ratio = 0.4, p = 0.01). For locally advanced rectal cancer, the administration of postoperative adjuvant 5FU/leucovorin chemotherapy after preoperative chemoradiation appeared to reduce recurrences, and improve the overall survival and the relapse-free survival, especially in high risk groups with post-chemoradiation stages II and III disease

Adjuvant Chemotherapy after Radical Resection of Squamous Cell Carcinoma in the Thoracic Esophagus: Who Benefits?

Background: A definitive combined modality therapy superior to surgery alone has not yet been found for esophageal cancer. This retrospective study investigated the impact of postoperative adjuvant chemotherapy in patients who underwent curative (R0) esophagectomy with radical lymphadenectomy. Study Design: Two hundred and eleven patients with a squamous cell carcinoma in the thoracic esophagus who underwent transthoracic curative (R0) esophagectomy with radical lymphadenectomy, such as 3-field lymphadenectomy or total 2-field lymphadenectomy, between 1988 and 2000, were retrospectively reviewed. Ninety-four patients received postoperative chemotherapy – 2 courses of cisplatin (CDDP) plus fluorouracil (5-FU) or vindesine (VDS) – while the other 117 patients received surgery alone. The overall survival rate was compared between the two groups after being stratified by the numbers of the metastasis- positive lymph nodes. Results: Only in the subgroup of patients with 8 or more lymph nodes metastasis- positive, the surgery-with-postoperative-chemotherapy group had a significantly better survival than the surgery-alone group. No significant difference was found in survival between the two groups in any other stratified subgroup. Conclusions: Postoperative adjuvant chemotherapy following curative (R0) esophagectomy with radical lymphadenectomy such as 3-field lymphadenectomy or total 2-field lymphadenectomy provided a benefit only in patients having metastasis in a large number – 8 or more – lymph nodes.