Number Of Adjuvant Chemotherapy Cycles Research Articles

MGMT Promoter Methylation: Prognostication beyond Treatment Response.

MGMT promoter methylation is related to the increased sensitivity of tumour tissue to chemotherapy with temozolomide (TMZ) and thus to improved patient survival. However, it is unclear how the extent of MGMT promoter methylation affects outcomes. In our study, a single-centre retrospective study, we explore the impact of MGMT promoter methylation in patients with glioblastoma who were operated upon with 5-ALA. Demographic, clinical and histology data, and survival rates were assessed. A total of 69 patients formed the study group (mean age 53.75 ± 15.51 years old). Positive 5-ALA fluorescence was noted in 79.41%. A higher percentage of MGMT promoter methylation was related to lower preoperative tumour volume (p = 0.003), a lower likelihood of 5-ALA positive fluorescence (p = 0.041) and a larger extent of resection EoR (p = 0.041). A higher MGMT promoter methylation rate was also related to improved progression-free survival (PFS) and overall survival (OS) (p = 0.008 and p = 0.006, respectively), even when adjusted for the extent of resection (p = 0.034 and p = 0.042, respectively). A higher number of adjuvant chemotherapy cycles was also related to longer PFS and OS (p = 0.049 and p = 0.030, respectively). Therefore, this study suggests MGMT promoter methylation should be considered as a continuous variable. It is a prognostic factor that goes beyond sensitivity to chemotherapy treatment, as a higher percentage of methylation is related not only to increased EoR and increased PFS and OS, but also to lower tumour volume at presentation and a lower likelihood of 5-ALA fluorescence intraoperatively.

Nomograms for predicting progression-free survival and overall survival after surgery and concurrent chemoradiotherapy for glioblastoma: a retrospective cohort study.

Glioblastoma (GBM) is the most common malignant brain tumor in adults. The prognosis of GBM patients is poor. Even with active standard treatment, the median overall survival is only 14.6 months. It is therefore critical to ascertain recurrence and search for factors that influence the prognosis of GBM. This study aimed to screen the variables related to the progression-free survival (PFS) and overall survival (OS) of GBM patients undergoing surgery and concurrent chemoradiotherapy, as well as propose a nomogram for individual risk prediction based on preoperative imaging parameters and clinicopathological variables readily available in clinical practice. We retrospectively analyzed 114 consecutive patients with GBM who underwent surgery and concurrent chemoradiotherapy at the Second Affiliated Hospital, Zhejiang University School of Medicine from January 1st, 2015, to June 1st, 2018. Twenty-four preoperative magnetic resonance imaging (MRI) parameters were extracted manually from the Picture Archiving and Communication System (PACS). Clinicopathological factors were extracted from the electronic medical record system (EMRS). Least absolute shrinkage and selection operator (LASSO) regression and Cox regression were used for feature selection and model prediction, respectively. The models were presented using nomograms, which were applied to identify the risk of recurrence and survival according to the score. The performance of the nomograms to predict PFS and OS was tested with C-statistics, calibration plots, and Kaplan-Meier curves. The results revealed that sex, Karnofsky performance score (KPS), O6-methylglucamine-DNA methyltransferase (MGMT) protein expression, number of adjuvant chemotherapy cycles with temozolomide (TMZ), and the MRI signature effectively predicted PFS; and sex, KPS, extent of surgery, number of TMZ cycles, and MRI signature effectively predicted OS. The nomogram revealed good discriminative ability (C-statistics: 0.81 for PFS and 0.79 for OS). In the nomogram of PFS, patients with a score greater than 122 were considered to have a high risk of recurrence. In the nomogram of OS, the cutoff score were 115 and 145, and then patients were classified as low, medium, and high risk. In conclusion, our nomograms can effectively predict the risk of recurrence and survival of GBM patients and thus can be a good guide for clinical practice.

Appropriate Number of Adjuvant Chemotherapy Cycles for Patients with Stage 2 or 3 Gastric Cancer After Curative Gastrectomy: A Multicenter Cohort Study.

Few studies have presented evidence pertaining to the adequate minimum number of adjuvant chemotherapy (AC) cycles required to achieve an oncologic benefit for gastric cancer. From January 2012 to December 2013, data from patients who underwent curative radical gastrectomy and consequently received AC for pathologic stage 2 or 3 gastric cancer at 27 institutions in South Korea were analyzed. The study enrolled 925 patients, 661 patients (71.5%) who completed 8 cycles of AC and 264 patients (28.5%) who did not. Compared with the mean disease-free survival (DFS) of the patients who completed 8 AC cycles (69.3months), the mean DFS of patients who completed 6 AC cycles (72.4months; p = 0.531) and those who completed 7 AC cycles (63.7months; p = 0.184) did not differ significantly. However, the mean DFS of the patients who completed 5 AC cycles (48.2months; p = 0.016) and those who completed 1-4 AC cycles (62.9months; p = 0.036) was significantly lower than the DFS of those who completed 8 AC cycles. In the multivariate Cox proportional hazards analysis, the mean DFS was significantly affected by advanced stage, large tumor size, positive vascular invasion, and number of completed AC cycles (1-5 cycles: hazard ratio 1.45; 95% confidence interval 1.01-2.08; p = 0.041). The current multicenter observational cohort study showed that the mean DFS for 6 or 7 AC cycles was similar to that for 8 AC cycles as an adjuvant treatment for gastric cancer.

Adjuvant chemotherapy is ineffective in patients with bladder cancer and variant histology treated with radical cystectomy with curative intent.

Adjuvant chemotherapy (ACT) is recommended for non-organ-confined bladder cancer (BCa) after radical cystectomy (RC) and pelvic lymph node dissection (PLND), but there are sparse data regarding its specific efficacy in patients with histological variants. The aim of our study was to evaluate the role of ACT on survival outcomes in patients with variant histology in a large multicenter cohort. We retrospectively evaluated data of 3963 patients with BCa treated with RC and bilateral PLND with curative intent at several institutions between 1999 and 2018. The histological type was classified into six groups: pure urothelial carcinoma (PUC) or squamous, sarcomatoid, micropapillary, glandular and neuroendocrine differentiation. Multivariable competing risk analysis was applied to assess the role of ACT on recurrence and cancer-specific mortality (CSM) in each histological subtype. Of the 3963 patients included in the study, 23% had variant histology at RC specimen and 723 (18%) patients received ACT. ACT was found to be significantly associated with reduced risk of recurrence (sub-hazard ratio [SHR]: 0.55, confidence interval [CI] 0.42-0.71, p < 0.001) and CSM (SHR: 0.58, CI 0.44-0.78, p < 0.001) in the PUC only, while no histological subtype received a significant benefit on survival outcomes (all p > 0.05) from administration of ACT. The limitation of the study includes the retrospective design, the lack of a central pathology review and the number of ACT cycles. In our study, the administration of ACT was associated with improved survival outcomes in PUC only. No histological subtype found a benefit in overall recurrence and CSM from ACT.

Survival Trends for Resectable Pancreatic Cancer Using a Multidisciplinary Conference: the Impact of Post-operative Chemotherapy.

Despite advances in various treatment modalities, surgical resection for pancreatic ductal adenocarcinoma (PDA) remains the only curative treatment. Data remains limited regarding survival rates for resectable PDA when managed by a multidisciplinary pancreas conference (MDPC). The aim of this study is to assess survival rates, identify significant predictors of mortality, and assess the benefits of adjuvant chemotherapy for resectable PDA following presentation at a MDPC. All patients presented from April 2013 to August 2016 with resectable PDA were discussed at a MDPC at a tertiary care center and were followed prospectively until November 2017. Survival analysis was performed using Kaplan-Meier for age, tumor size, tumor differentiation, T-stage, lymph node status, and completion of adjuvant chemotherapy cycles. Independent predictors of survival were determined using multivariate Cox regression modeling. After MDPC consensus and exclusions, total of 64 patients underwent successful surgery. Amongst this cohort, 1-, 2-, and 3-year survival was 78.13%, 46.30%, and 27.27%, respectively. A total of 37 patients (58%) initiated and 16 patients (25%) finished chemotherapy following surgery. Log-rank analysis revealed that tumor size, age, surgical margins, lymph node status, and number of adjuvant chemotherapy cycles received significantly influenced post-operative survival. Tumor size (p < 0.001), lymph node status (p = 0.035), and number of adjuvant chemotherapy cycles (p = 0.041) remained significant after multivariate Cox regression model. Our results suggest that patients with PDA with tumor size > 50mm and/or lymph node involvement have poor outcomes despite being surgically resectable. Successful completion of adjuvant chemotherapy has better survival outcomes as compared with incomplete or no adjuvant chemotherapy. The role of alternative management such as down-staging with neoadjuvant therapy should be considered.

Nomogram incorporated the number of adjuvant chemotherapy cycles for predicting the prognosis in stage II-III rectal cancer patients without neoadjuvant therapy.

e15163 Background: Current recommendations for adjuvant chemotherapy in rectal cancer are based on the studies in colon cancer. However, it is now known that rectal cancer differs from colon cancer significantly regarding clinical course and biology. No RCTs in the TME era have evaluated the value of postoperative chemotherapy and are unlikely to be performed as neoadjuvant treatment has become a “gold standard” approach. However, we found that not all patients with locally advanced rectal cancer underwent neoadjuvant chemoradiotherapy before TME in real-world clinical practice in China. Whether the number of adjuvant chemotherapy cycles is significantly related to the prognosis of these patients deserves further study. Methods: A total of 246 patients with stage II-III rectal cancer from January 2013 to April 2018 were enrolled. All patients underwent surgery and had not received neoadjuvant therapy. The survival curve was drawn by the Kaplan-Meier method, and the log-rank method was used for statistical analysis. The Cox proportional hazard model was used for multivariate analysis to determine the independent prognostic factors. Then, MFP(Multiple Fractional Polynominal) and stepwiseAIC were used for variable selection. The R software was used to establish the nomogram. The bootstrap method was employed to internal verification. Concordance index(C-index) was applied to evaluate the predictive power of nomogram. Calibration curves were drawn to compare the 3-year overall survival rate predicted by nomogram and that of actual observation. Results: 87.8% of patients received adjuvant chemotherapy including oxaliplatin combined with fluorouracil or capecitabine. Univariate and multivariate analysis showed that the number of adjuvant chemotherapy cycles was independent prognostic factors. Patients who received more than 5 cycles of chemotherapy (HR = 0.09, 95%CI(0.01,0.80)) had a significantly better overall survival than patients with less than 5 cycles (HR = 0.33,95%CI(0.12,0.89)) or no chemotherapy (p &lt; 0.05).Through MFP and the stepwiseAIC screening, a nomogram was established based on CEA, PLR, N, and the number of chemotherapy cycles, and the C-index of the model was 0.86. Conclusions: The number of adjuvant chemotherapy cycles is an independent prognostic factor in stage II-III rectal cancer patients without neoadjuvant therapy. Moreover, nomogram incorporated the number of chemotherapy cycles was accurate and visible.

Optimizing the treatment of ovarian cancer: Neoadjuvant chemotherapy and interval debulking versus primary debulking surgery for epithelial ovarian cancers likely to have suboptimal resection

ObjectiveTo: a) identify prognostic factors in patients with epithelial ovarian cancer treated with neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS), and b) compare post-surgical survival between patients treated with NACT/IDS for presumed unresectable disease and stage IIIC/IV patients who underwent suboptimal primary debulking surgery (PDS). MethodsThis was a retrospective study of consecutive stage IIIC or IV patients undergoing IDS after NACT at Mayo Clinic from January 2007 to December 2013. A subset of patients receiving NACT/IDS for the indication of unresectable disease were matched 1:1 on age and stage to a cohort of patients who underwent suboptimal PDS between 2003 and 2011. Hazard ratios and corresponding 95% confidence intervals were estimated from Cox proportional hazards models. ResultsWe identified 87 patients treated with NACT/IDS: the median OS and PFS following surgery was 2.4 and 1.0years, respectively. Factors associated with significantly worse OS were older age (adjusted HR 1.60 per 10-year increase in age, 95% CI 1.18, 2.16) and elevated CA-125 before IDS (adjusted HR 2.30 for CA-125 >35U/mL, 95% CI 1.25, 4.23). Number of adjuvant chemotherapy cycles administered did not have a significant effect on survival. In the matched cohort analysis of presumed unresectable cases undergoing NACT/IDS vs suboptimal PDS cases (n=45 each), the NACT/IDS group had a significant OS advantage (HR 0.53; 95% CI 0.32, 0.88), and fewer patients experienced a 30-day postoperative Accordion grade 3/4 complication (11% vs 36%, P=0.01). ConclusionsYounger age and normalization of CA-125 prior to IDS are associated with improved survival with NACT/IDS. For primary EOC where resection to residual disease of 1cm or less is unlikely, NACT/IDS is associated with improved survival and reduced perioperative morbidity compared to PDS. As these patients are likely best served by NACT/IDS, more reliable predictors of resectability would be valuable.

Adjuvant Chemotherapy After Radical Cystectomy for Urothelial Bladder Cancer: Outcome and Prognostic Factors for Survival in a French Multicenter, Contemporary Cohort

BackgroundIn the past decade, adjuvant chemotherapy (AC) after radical cystectomy (RC) was preferred worldwide for patients with muscle-invasive urothelial bladder cancer. In this study we aimed to determine the outcome of patients who received AC and evaluated prognostic factors associated with survival. Patients and MethodsWe retrospectively analyzed 226 consecutive patients treated in 6 academic hospitals between 2000 and 2009. Multivariate Cox proportional hazards regression adjusted for center to estimate adjusted hazard ratios (HRs) with 95% confidence intervals were used. ResultsThe median age was 62.4 (range, 35-82) years. Patients had pT3/pT4 and/or pN+ in 180 (79.6%) and 168 patients (74.3%), respectively. Median lymph node (LN) density was 25% (range, 3.1-100). Median time between RC and AC was 61.5 (range, 18-162) days. Gemcitabine with cisplatin, gemcitabine with carboplatin, and MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin) regimens were delivered in 161 (71.2%), 49 (21.7%), and 12 patients (5.3%) of patients, respectively. The median number of cycles was 4 (range, 1-6). Thirteen patients (5.7%) with LN metastases also received adjuvant pelvic radiotherapy (ART). After a median follow-up of 4.2 years, 5-year overall survival (OS) was 40.7%. In multivariate analysis, pT ≥3 stage (HR, 1.73; P = .05), LN density >50% (HR, 1.94; P = .03), and number of AC cycles <4 (HR, 4.26; P = .001) were adverse prognostic factors for OS. ART (HR, 0.30; P = .05) tended to provide survival benefit. ConclusionClassical prognostic features associated with survival are not modified by the use of AC. Patients who derived benefit from AC had a low LN density and received at least 4 cycles of treatment.

Impact of Adjuvant Chemotherapy Cycles on Prognosis of Resectable Stomach Cancer: A Retrospective Analysis

The aim of this study was to investigate the effects of adjuvant chemotherapy cycles on the prognosis of patients with post-operative stomach cancer through retrospective analysis. A total of 128 patients with gastric cancer who underwent gastrectomy, followed by adjuvant chemotherapy consisting of epirubicin, cisplatin or oxaliplatin, leucovorin, and 5-fluorouracil, according to a defined schedule, were divided into three groups according to the number of chemotherapy cycles: Group I (<6 cycles); Group II (6 cycles); and Group III (>6 cycles). The 5-year overall survival (OS) was 20.8% in Group I, 45.0% in Group II, and 42.9% in Group III, with a median follow-up of 43 months. The 5-year relapse-free survival (RFS) was 15.1% in Group I, 40% in Group II, and 40% in Group III. The OS and RFS in Groups II and III were significantly better than in Group I (OS, p = 0.002 and p=0.003; RFS, P<0.001 and P=0.002). There was no difference in OS (p = 0.970) or in RFS (p = 0.722) between Groups II and III. Multivariate Cox hazard analysis determined that the number of adjuvant chemotherapy cycles was an independent factor that influenced OS and RFS. Six cycles of adjuvant chemotherapy gave encouraging outcomes in patients with resectable gastric cancer. Further prospective randomized controlled investigations are warranted in a multi-center setting.

Lymph node density and number of adjuvant chemotherapy cycles for node-positive resected bladder cancer: University of Iowa experience

e16126 Background: Although its survival benefit is unclear, adjuvant chemotherapy (CT) is commonly utilized for node-positive bladder cancer after radical cystectomy (RC) and lymph node (LN) dissection. The ideal number of CT cycles is also unknown. Previous studies in patients with metastatic disease administered up to 6 cycles. Lymph node density (LND) (ratio of positive LN/total LN) has been shown to be more important than nodal TNM stage in predicting outcomes after RC, and suggested a 20% LND cutoff for prognosis. This finding also accounted for adjuvant chemotherapy (yes vs. no). We evaluated the long-term outcomes of node-positive pts after RC, according to the number of cycles of adjuvant CT received and adjusting for LND. Methods: The study was IRB approved. Patients still alive were required to give informed consent and accrual is ongoing. Pathological and survival variables of pathologically node-positive pts who underwent RC at the University of Iowa in the last 5 yrs and then received adjuvant CT were retrospectively evaluated. Results: 22 pts have been evaluated to date. Median age was 62 (37–86). Median number of LNs resected was 19.5 and median LND was 19% (3–47). Median survival was 17 mo (10–67). 21 pts received a platinum-gemcitabine combination. The table shows the pt distribution according to no. of CT cycles, LND and number of &gt; 2 yr survivors. Median survival was 17 mo both for pts with LND ≤ 20% and &gt;20% . Median survival of pts with ≤ 4 cycles of CT was 16.5 mo (11–67), with 4 patients still alive at 14–67 months. Median survival of pts who received &gt; 4 cycles of adjuvant CT was 17 mo (10–44), with 3 pts still alive at 29–39 months. Conclusions: The pt distribution table suggests that patients with high LND may have been sicker, and thus less able to receive as many CT cycles. This study is limited by its retrospective nature and small current sample. Accrual is ongoing and updated data will be available. Prospective adjuvant trials could stratify or randomize patients based on LND. [Table: see text] No significant financial relationships to disclose.