Time To Adjuvant Chemotherapy Research Articles

A minimally invasive approach to colon cancer resection improves time to adjuvant chemotherapy

Background: Colorectal cancer is the second leading cause of cancer death in the United States each year. The use of adjuvant chemotherapy after surgical resection of colon cancer has been associated with survival benefit. Timely initiation of adjuvant chemotherapy has been shown to have an effect on overall survival (OS) and disease-free survival. This study examined the relationship between surgical subspecialty and postoperative complications, as well as operative approach on the effect of time to adjuvant chemotherapy (TTAC) at a single institution.

5-Fu-Based Doublet Regimen in Patients Receiving Perioperative or Postoperative Chemotherapy for Locally Advanced Gastric Cancer: When to Start and How Long Should the Regimen Last?

BackgroundThe duration and the optimal time to adjuvant chemotherapy (TAC) in locally advanced gastric cancer (LAGC) have net not been sufficiently demonstrated. Sequential adjuvant chemotherapy (AC) after neoadjuvant chemotherapy plus gastrectomy is increasingly utilized, making the question more complicated.Patients and MethodsData were collected from patients with LAGC who underwent 5-Fu-based doublet regimens as adjuvant treatment after gastrectomy in a single-center database. TAC and duration (cycles) were used to evaluate survival outcomes.ResultsA total of 816 patients were included. Patients received over six cycles and TAC less than 42 days significantly correlated with better survival (log-rank Ptrend<0.001). The analysis of TAC and number cycles were separately applied in perioperative chemotherapy (PEC) and postoperative chemotherapy (POC) group using Cox regression. The number of cycles revealed a statistical significance improving OS rate both in POC (HR=0.904, 95% CI=0.836–0.977, P=0.011) and PEC (HR=0.887, 95% CI=0.798–0.986, P=0.026), while only in POC did the TAC show an increasing trend of risk with borderline significance (OS: HR=1.008, 95% CI=0.999–1.018, P=0.094; PFS: HR=1.009, 95% CI=1.000–1.018, P=0.055). A spline model demonstrates the less improvement in survival after cycles of chemotherapy reaching six.ConclusionOur findings suggest that TAC is more likely to downregulate the survival benefit in POC rather than PEC, while overall survival is susceptible to cumulative cycles of chemotherapy in both groups. Furthermore, six cycles of chemotherapy tended to reach the maximum survival benefits. Prospective confirmation is required.

Prolonged Time to Adjuvant Chemotherapy Initiation Was Associated with Worse Disease Outcome in Triple Negative Breast Cancer Patients

The optimal time to adjuvant chemotherapy (TTC) for breast cancer (BC) patients remains uncertain. Herein, we aim to evaluate the association between TTC and prognosis among different subtypes in modern era of adjuvant chemotherapy. BC patients receiving operation and adjuvant chemotherapy between January 2009 and December 2015 were included. Enrolled patients were categorized into TTC ≤4 weeks and >4 weeks groups. Relapse-free survival (RFS) and overall survival (OS) were compared according to TTC and analyzed among different BC molecular subtypes. A total of 2611 patients were included. Elder age (P = 0.005), more comorbidities (P <0.001), breast-conserving surgery (P = 0.001), non-invasive ductal carcinoma (P = 0.012), and HER2-positivity (P <0.001) were associated with prolonged TTC. Among whole BC population, no significant difference was observed between two TTC groups in terms of RFS (P = 0.225) or OS (P = 0.355). However, for triple negative (TNBC) patients, TTC >4 weeks was independently related with worse RFS (5-year RFS 81.9% vs 89.3%; HR, 1.89; 95% CI, 1.09 to 3.27; P = 0.024) and OS (5-year OS 84.0% vs 94.0%; HR, 2.49; 95% CI, 1.30 to 4.76; P = 0.006) compared with those TTC ≤4 weeks. Prolonged TTC >4 weeks after BC surgery was not associated with worse survival outcomes in the whole BC patients. However, TTC >4 weeks may increase risk of relapse or death in TNBC patients, which deserves further clinical evaluation.

Does time to adjuvant chemotherapy (TTC) affect outcomes in patients with triple-negative breast cancer?

A recent study reported that time to adjuvant chemotherapy (TTC) > 30days was significantly associated with worse OS and DFS in triple-negative breast cancer (TNBC). Earlier studies, however, found that worse outcomes were associated with TTC > 60days or > 90days. As the trend for mastectomy with reconstruction continues to rise, TTC of < 30days is often not feasible due to wound-healing issues in some of these patients. To elucidate the impact of TTC, we sought to evaluate the clinical outcomes associated with TTC in a contemporary cohort treated for TNBC at a single institution. A single-institution database was queried to identify nonmetastatic TNBC patients who received adjuvant chemotherapy from 2009 to 2018. TTC was defined as interval between date of surgery and adjuvant chemotherapy start date. Median TTC was used to divide our cohort into four quartiles; ≤ 31, 32-42, 43-56, and > 56days. Logrank, Kaplan-Meier, and inverse probability weighting (IPW) tests were used to analyze disease-free (DFS) and overall survival (OS). The mean TTC of our study cohort (n = 724) was 48days (median TTC = 42days). Black race, mastectomy without adjuvant radiation, and mastectomy with immediate reconstruction were associated with delayed TTC (all p-values < 0.01). In multivariate IPW analysis, TTC > 56 (n = 173) days did not impact DFS or OS compared to TTC ≤ 31 (n = 198) days (p = 0.27 and p = 0.21, respectively). Similar results were seen during subgroup analysis for groups identified as higher risk for delayed TTC. Our results demonstrated that TTC was not significant or significantly associated with DFS or OS in patient receiving chemotherapy for operable TNBC. Our results were reassuring for patients electing mastectomy with immediate reconstruction, who may experience a longer TTC.

An analysis of the influence of infection on overall survival rates, following modified posterior pelvic exenteration for advanced ovarian cancer.

Objectives The aim of our study has been to determine the association between the appearance of infection after modified posterior pelvic exenteration (MPE) and TTC (time to adjuvant chemotherapy) and to examine whether the infection impacts clinical results by delaying the start of chemotherapy. Material and methods The present, retrospective study analyzed 77 patients who had undergone MPE followed by adjuvant chemotherapy. Either no residual tumor or tumor less than 2.5 mm was achieved in 76.7% of these patients. Patients were divided into two subgroups for comparison; the first group consisted of 41 patients with infections, the second group of 36 patients without infections. Infection after surgery was monitored within a 90-day postoperative period. Median TTC and OS (overall survival) was determined for those patients who developed infection as well as for those who did not. Results The expected 5-year survival rate was 0.40 (SD=0.09) for those patients without infection and 0.17 (SD=0.07) for those patients with infection. The survival curves of patients with infection and those without infection were statistically significantly different (p=0.038). Median TTC differed significantly for those patients who developed infection vs those patients who did not develop infection (37days vs 27.5 days, p=0.024), and patients without infection were statistically more likely to receive chemotherapy within 25 days following surgery than in the subsequent 25-42-day period compared to those patients who did develop infection (p=0.048). No statistically significant differences were found between the groups in relation to the initiation of chemotherapy within 42 days (p=0.445). Conclusions The absence of postoperative infection was associated with a better survival. Patients with infection were noted a longer time interval from surgery to start of chemotherapy without negative impact to OS.

The effect of immediate breast reconstruction on the timing of adjuvant chemotherapy: a systematic review.

Adjuvant chemotherapy is often needed to achieve adequate breast cancer control. The increasing popularity of immediate breast reconstruction (IBR) raises concerns that this procedure may delay the time to adjuvant chemotherapy (TTC), which may negatively impact oncological outcome. The current systematic review aims to investigate this effect. During October 2014, a systematic search for clinical studies was performed in six databases with keywords related to breast reconstruction and chemotherapy. Eligible studies met the following inclusion criteria: (1) research population consisted of women receiving therapeutic mastectomy, (2) comparison of IBR with mastectomy only groups, (3) TTC was clearly presented and mentioned as outcome measure, and (4) original studies only (e.g., cohort study, randomized controlled trial, case–control). Fourteen studies were included, representing 5270 patients who had received adjuvant chemotherapy, of whom 1942 had undergone IBR and 3328 mastectomy only. One study found a significantly shorter mean TTC of 12.6 days after IBR, four studies found a significant delay after IBR averaging 6.6–16.8 days, seven studies found no significant difference in TTC between IBR and mastectomy only, and two studies did not perform statistical analyses for comparison. In studies that measured TTC from surgery, mean TTC varied from 29 to 61 days for IBR and from 21 to 60 days for mastectomy only. This systematic review of the current literature showed that IBR does not necessarily delay the start of adjuvant chemotherapy to a clinically relevant extent, suggesting that in general IBR is a valid option for non-metastatic breast cancer patients.Electronic supplementary materialThe online version of this article (doi:10.1007/s10549-015-3539-4) contains supplementary material, which is available to authorized users.

A retrospective analysis on the effect of time to adjuvant chemotherapy (TTAC) from surgery in stage III colon cancer.

e17562 Background: A narrow therapeutic window exists within which to initiate adjuvant chemotherapy (AC) post surgery and delays may impact disease free (DFS) and overall survival (OS). In a publi...

Time to adjuvant chemotherapy (TTAC) after open or laparoscopic resection surgeries in colorectal cancers (CRC).

768 Background: This single institution retrospective study evaluates the reason for delay in Time To Adjuvant Chemotherapy (TTAC) from curative resection surgery to start of adjuvant therapy in CRC. The reason for this study was to determine if type of surgery (laparoscopic versus open) increased TTAC of which evidence indicates poorer disease free survival and overall survival (Biagi J, Raphael M, Mackillop W, Kong W, King W, Booth C. Association between time to initiation of adjuvant chemotherapy and survival in colorectal cancer: a systematic review and meta-analysis. JAMA, 305(22):2335-42. doi: 10.1001/jama.2011.749.) Methods: CRC patients treated at St. Michael’s Hospital in Toronto, Canada were included if diagnosed with stage II or III disease, underwent curative resection surgery between January 1, 2006, and December 31, 2012, and either received systemic adjuvant chemotherapy or surveillance protocol. Results: Among 259 patients, 92 patients (35.7%) underwent curative laparoscopic resection and 166 open resection (64.3%). Intraoperative and/or postoperative complications were experienced in 73 patients. Complications were less prevalent among patients who underwent laparoscopic surgery versus open resection (11.9% vs. 36.8%; p&lt;0.0001). Of these 73 complications, wound infection (39.7%), intraoperative procedural complication (14.3%), and postoperative gastrointestinal complications (6.4%) were most prevalent. After adjusting for complication and clustering within the operating surgeon, there were no statistical differences in TTAC between open (51.310 ± 1.7 days) and laparoscopic (49.2 ± 1.6 days) resection surgeries (p=0.1996). However, presence of a complication was associated with delay in TTAC (HR 0.501; 95% CI, 0.43-0.58; p&lt;0.001). Conclusions: TTAC in CRC patients does not differ statically for each type of resection surgery. However, presence of a complication is associated with delays in TTAC and is over three-fold more prevalent in open than laparoscopic resections. Therefore, there is an increased risk of delay in TTAC for open resection surgeries than laparoscopic resections due to a higher prevalence of surgical complications.

Time to Adjuvant Chemotherapy and Survival Outcomes Among Patients With Stage 2 to 3 Rectal Cancer Treated With Preoperative Chemoradiation

BackgroundPrevious studies have evaluated the impact of time to adjuvant chemotherapy (AC) on survival in early-stage colon cancer. However, the optimal time to adjuvant chemotherapy (TTAC) in rectal cancer remains unclear. The objective of this study was to identify an optimal TTAC and determine its prognostic effect in stage 2 to 3 rectal cancer. MethodsPatients with stage 2 to 3 rectal cancer treated with preoperative chemoradiation and postoperative AC between 1999 and 2008 were included. Predetermined time points of 4, 6, 8, and 12 weeks from date of surgery were analyzed. Cut-point analysis was then used to determine an optimal TTAC, and overall survival at the identified cut-point was evaluated. ResultsA total of 328 eligible patients were identified with a median age of 61 years (range 22-85 years), 70% male, and 75% stage 3 disease. The median TTAC was 7.0 weeks. Initiation of AC at 6 weeks from date of surgery was associated with a significant survival benefit (hazard ratio 0.52, 95% confidence interval 0.31-0.90, P = .017), while no significant association was seen at 4, 8 or 12 weeks (P > .05). The cut-point analysis identified an optimal TTAC of 5.6 weeks association with improved survival compared to those with a TTAC greater than 5.6 weeks (hazard ratio 0.42, 95% confidence interval 0.22-0.82, P = .0087). This cut-point was also found to be a significant prognostic factor in multivariable analysis (P = .04) adjusted for Eastern Cooperative Oncology Group performance status, age, gender, stage, margin status, and grade. ConclusionsThis study suggests that initiation of AC within an earlier time frame is associated with improved overall survival.

Predicting the risk of gastrointestinal (GI) toxicity in early colon cancer (CC) patients (pts) treated with adjuvant chemotherapy: Developing a GI toxicity scoring system.

420 Background: Baseline demographics and clinical factors may contribute to a pt’s overall risk for developing chemotherapy-related GI toxicity, such as nausea, vomiting, and diarrhea. We aimed to develop a GI toxicity scoring system to better stratify early CC pts who may be at higher risk of developing GI toxicity from adjuvant FOLFOX chemotherapy. Methods: Pts diagnosed with early CC from 2005 to 2008 and treated with FOLFOX at the British Columbia Cancer Agency were reviewed. GI toxicities of interest included (1) nausea/vomiting, (2) diarrhea, and (3) any GI side effects. Baseline variables that were analyzed consisted of age, sex, ECOG, time to adjuvant chemotherapy (TTAC), and laboratory parameters. Stepwise regression was used to develop a multivariate model for each toxicity and a weighted risk scoring system was subsequently devised based on the magnitude of the parameter estimates in the multivariate model. Results: In total, 475 pts were included: median age was 62 years (range 26-89), 16.2% were aged &gt;70 years, and 54.5% were men. The majority (90.1%) was ECOG 0/1. Independent predictors for nausea/vomiting included age &gt;70 years (OR 2.46, 95%CI 1.3-4.8, p=0.011), GFR &lt;50 (OR 1.68, 95% CI 1.1-2.7, p=0.025), and TTAC &gt;8 weeks (OR 1.33, 95% CI 0.9-2.1, p=0.14) whereas independent predictors for diarrhea included age &gt;70 years (OR 1.44, 95% CI 0.79-2.62, p=0.12) and GFR &lt;50 (OR 1.67, 95% CI 1.1-2.6, p=0.018). The multivariate model for the risk of any GI toxicity included age &gt;70 years (OR: 2.61, 95% CI 1.1-6.1, p=0.049), GFR &lt;50 (OR 1.69, 95% CI 1.1-2.6, p=0.0038), and TTAC &gt;8 weeks (OR 1.79, 95% CI 1.2-2.7, p=0.0059). Points were assigned: 2 points for long TTAC and poor GFR and 1 point for advanced age. The study cohort was classified into their risk groups based on their score (Table). Conclusions: We developed a simple 5-point scoring system to stratify early CC pts receiving adjuvant FOLFOX into low and high risk groups for GI toxicity based on baseline clinical factors. Further validation of this scoring system is required. [Table: see text]

Predicting toxicities from adjuvant treatment in a population-based cohort of early colon cancer (CC) patients (pts): A strategy to improve use of curative chemotherapy.

412 Background: CC pts treated with chemotherapy are at risk of experiencing a number of toxicities. The identification of pts who may be at a higher risk of developing toxicities allows clinicians to be more vigilant in preventing and managing side effects early, thus enabling more optimal delivery of chemotherapy. Our aim was to determine clinical factors associated with toxicities from adjuvant FOLFOX in early CC. Methods: Pts diagnosed with stage III CC from 2005 to 2008, seen at any 1 of 5 regional cancer centers of the British Columbia Cancer Agency, and treated with adjuvant FOLFOX chemotherapy were reviewed. We evaluated various toxicities, including gastrointestinal, hematologic, cardiovascular, and neurological side effects. Baseline and clinical factors were assessed in univariate and multivariate models to determine potential predictors for each of the different chemotherapy toxicities. Results: In total, 475 pts were included: median age was 62 years (range 26-89), 16.2% were aged &gt;70 years, and 54.5% were men. In terms of function, the majority (90.1%) was ECOG 0/1. Time to adjuvant chemotherapy (TTAC) &gt;8 weeks (OR 1.91, 95% CI 1.8-3.1, p=0.006) and renal dysfunction with a GFR &lt;50 (OR 1.69, 95% CI 1.1-2.6, p=0.0038) were significantly associated with higher odds of any GI toxicity. Likewise, TTAC &gt;8weeks (OR 2.8, 95% CI 1.5-5.2, p=0.002), ECOG PS &gt;1 (OR 2.86, 95% CI 1.2-6.7, p=0.016), and low white blood cell count &lt;6.4 (OR 2.32, 95% CI 1.3-4.0, p=0.0043) were correlated with a greater risk of significant neutropenia. Multiple toxicities were more prevalent among those who waited &gt;8 weeks to initiate adjuvant FOLFOX (OR 1.69, 95%CI 1.1-2.7, p=0.03). Further, advanced age &gt;70 years was an indepenent risk factor for worse nausea and diarrhea. Conclusions: Consideration of important baseline characteristics such as TTAC, advanced age, renal function, and specific laboratory parameters when recommending adjuvant FOLFOX can be useful in identifying patients with increased likelihood of toxicities. This group of patients may benefit from increased monitoring in order to enable optimal doses of curative chemotherapy to be delivered.

Reasons for delay in time to initiation of adjuvant chemotherapy (AC) for colon cancer (CC).

e14553 Background: AC improves survival among patients with colon cancer. Two meta-analyses have demonstrated a decrease in survival with increasing time to AC (TTAC). Here, we examine the predominant factors leading to delay in TTAC. Methods: Individual medical records of 565 patients with CC who initiated AC Aug 2005-Nov 2010 in Eastern Ontario were reviewed to capture patient and treatment characteristics including: medical comorbidities, post-operative complications, the reason if AC was not ordered after initial medical oncology (MO) consultation, dates of surgery, referral to MO, MO consult, central venous catheter (CVC) insertion, and first cycle of AC. Patients were then categorized into two groups: (i) medical/surgical reason for delay (MSRD), defined as post-operative complications or intercurrent illness, and (ii) No MSRD. No MSRD patients were further subcategorized as post-MO delay (PMOD), defined as AC deferred at time of consultation due to patient preference or further investigations required, vs. No PMOD. A multivariate logistic regression model was used to determine factors associated with TTAC &gt; 8 weeks (w). Results: In the No MSRD group (n= 423), 25% (n=107) were subdivided into the PMOD subgroup. On multivariate analysis, TTAC &gt;8w was significantly associated with the presence of a MSRD [OR = 2.4 (1.6-3.9), p = &lt;0.001] or PMOD [OR = 3.3 (1.9-5.6), p = &lt;0.001]. No other significant associations were found, including oral vs. IV AC. Proportion of cases with TTAC &gt;8w in the subgroups were: MSRD 76.1% (n = 108); PMOD 80.4% (n = 86); No PMOD 57.6% (n = 182). Conclusions: MSRD and PMOD are strong predictors of increased TTAC; however, the majority of patients have no MSRD or PMOD. TTAC in this group is 9 weeks. This suggests that TTAC is modifiable, and likely reflects delays in referral, consultation, and chemotherapy booking. [Table: see text]

Association of time to adjuvant chemotherapy (TTAC) and overall survival among patients with rectal cancer treated with preoperative radiation.

461 Background: Studies suggest that delayed adjuvant chemotherapy (AC) beyond 8 weeks is associated with inferior survival in early-stage colon cancer (CA). The optimal TTAC in rectal CA remains unclear. The objective of this study was to determine the prognostic effect of TTAC in stage II and III rectal CA treated with standard preoperative (op) chemoradiation. Methods: Patients with stage II/III rectal CA treated with pre-op chemoradiation, received post-op AC, and referred to the British Columbia Cancer Agency between 1999 and 2008 were included. Univariate and multivariate analyses were conducted using Kaplan Meier and Cox regression methods to evaluate the association between TTAC and outcomes. X-tiles cut-point analysis was performed to determine the optimal TTAC. Results: A total of 327 eligible patients were identified: median age 61 (range 22-85), 70% male, and 75% stage III. In terms post-op AC, 51% received 5-fluorouracil (5-FU), 32% received capecitabine, 12% received 5-FU and oxaliplatin, and 5% received other chemotherapy. Median TTAC was 7.0 weeks (wks) (range 1.6-33.3 wks). Cut-point analysis revealed the optimal TTAC to be 5.6 wks (HR: 0.42, 95%CI 0.22-0.82, p=0.0087). Initiation of AC within optimal TTAC (5.6 wks) and 6 wks from date of surgery (sx) was associated with a significant survival benefit while no significant effect was seen at 8 wks. TTAC of ≤ 6 wkswas found to be a significant prognostic factor in multivariate analysis (p=0.047) adjusted for ECOG, age, sex, stage, margin status, and grade. In stratified analysis by stage, patients with stage III disease benefited from AC (p=0.018) while those with stage II did not (p=0.71). Conclusions: In this study, the optimal TTAC was 6 weeks or less. Initiation of AC within this time frame was associated with improved OS. This is less than the optimal timeframe indicated in the literature for colon CA. [Table: see text]

Reasons for delay in time to initiation of adjuvant chemotherapy (AC) for colon cancer (CC).

548 Background: AC improves survival among patients with colon cancer. Two meta-analyses have demonstrated a decrease in survival with increasing time to AC (TTAC). In this study, we examined individual patient charts to determine reasons for delay in AC. Methods: Medical records of patients with CC who initiated AC Aug 2005-Nov 2010 at the Cancer Centre of Southeastern Ontario were reviewed to capture patient, disease, and treatment characteristics including: medical comorbidities, post-operative complications, whether AC was or was not ordered after initial consultation, and the reasons behind the decision. Dates of surgery, referral, consult, central venous catheter (CVC) insertion, and first cycle of AC were recorded. Patients were then categorized into Group 1-medical/surgical reason for delay (MSRD), defined as presence of post-operative complications or intercurrent medical illness, and Group 2–no MSRD. In Group 2, patients were further categorized as having a non-MSRD, defined as patients in whom AC was deferred at time of consultation due to patient preference and/or further investigations required, vs none. A multivariate logistic regression model was used to determine factors associated with TTAC &gt; 8 weeks (w). Results: For 171 patients: Mean age - 67; 52% male; 79% stage 3; IV AC – 80%, Oral AC – 20%. TTAC for all cases was 8.3 ± 2.3w. Mean intervals ± SD between surgery and TTAC in weeks were: surgery to referral 3.1 ± 2.0; referral to consult 2.5 ± 2.3; consult to oral AC 2.0 ± 2.1; for IV AC, consult to CVC 2.2 ± 1.3, and CVC to AC 0.7 ± 0.8. TTAC did not differ between patients with comorbidities (N= 89) and those without (N=82), p= 0.64, but was greater for patients in Group 1 (N=41 with MSRD) vs Group 2 (N = 130), p= 0.002. In Group 2, 43.8% (N=57) had TTAC &gt; 8w while only 20% of cases (n=26) had a non-MSRD. Factors associated with TTAC&gt;8w were MSRD [OR=5.6 (2.3-13.7), p = &lt;0.001] and non-MSRD [OR=6.7 (2.3-19.5), p = &lt;0.001]. Conclusions: Although medical/surgical complications are a strong predictor of delayed TTAC, this only applies to a small proportion of cases. Accordingly, in most patients TTAC&gt;8w is unrelated to their post-operative medical condition and likely reflects health system and logistical issues.

Time to adjuvant chemotherapy and survival in non–small cell lung cancer

The time interval between surgery and initiation of adjuvant chemotherapy (ACT) may impact survival in colorectal and breast cancers. This is the first report describing the association between time to adjuvant chemotherapy (TTAC) and survival in non-small cell lung cancer (NSCLC). All cases of NSCLC diagnosed in Ontario, Canada, from 2004 to 2006 who underwent surgical resection (n = 3354) were identified using the Ontario Cancer Registry. TTAC was defined as the interval between dates of surgery and initiation of ACT. Factors associated with TTAC greater than 10 weeks were evaluated by logistic regression. The Cox proportional hazards model was used to describe the effect of delayed TTAC (analyzed as a continuous variable) on overall survival. Among the 1032 cases treated with ACT, the median TTAC was 8 weeks (range, 1-16 weeks); 35% of cases initiated ACT more than 10 weeks after surgery. Rates of TTAC greater than 10 weeks varied widely across regions (11%-50%, P = .001). There was no significant association between increased comorbidity and delayed TTAC; there was a trend toward greater delay in TTAC with longer postoperative hospital stay (P = .054) and postoperative readmission to hospital (P = .056). Male sex, higher stage of disease, greater comorbidity, and more extensive surgery were independently associated with inferior survival. TTAC was not associated with overall survival (odds ratio = 1.00, 95% confidence interval = 0.99-1.00). One-third of NSCLC patients treated with ACT in the general population start ACT beyond 10 weeks after surgery. Delayed TTAC does not appear to be associated with inferior survival in NSCLC.

The effect of delay in time to adjuvant chemotherapy (TTAC) on survival in breast cancer (BC): A systematic review and meta-analysis.

1128 Background: The optimal timing from BC surgery to initiation of adjuvant chemotherapy (AC) is unknown. We report a systematic review and meta-analysis to determine the relationship between TTAC and survival. Methods: A systematic review of literature was completed to identify studies that described the relationship between TTAC and survival. Studies were only included if the distribution of relevant prognostic factors was adequately described, and either comparative groups were balanced or results adjusted for the prognostic factors. Hazard ratio (HR) and TTAC for overall survival (OS) and disease free survival (DFS) from each study were converted to a regression coefficient (β) and standard error (SE) corresponding to a continuous representation per 4 weeks of TTAC. The adjusted β from individual studies were combined using a fixed-effect model. Inverse-variance (1/SE2) was used to weight individual studies. Publication bias was investigated using funnel plots and the trim-and-fill approach. Results: We identified 4 eligible studies for OS, and 5 for DFS, all fully published manuscripts. The OS studies involved 15,327 patients; two were randomized trials and 2 were cohort studies; one study reported TTAC as a binary variable and three had 4 TTAC categories. Meta-analysis demonstrated that a 4-week increase in TTAC was associated with an OS HR of 1.06 (95% CI 1.02-1.10), and DFS HR of 1.08 (95% CI 1.03-1.14). The analyses for heterogeneity justified the use of a fixed-effect model. These TTAC associations remained significant after analysis for potential publication bias, and when the analysis was repeated excluding the studies of largest weight. Conclusions: This study demonstrates a 6% increase in the risk of death for each 4 week delay to initiation of AC for BC. Our results were consistent for both OS and DFS, and remained significant after correction for publication bias. These findings indicate that clinicians and oncology health systems managers should monitor TTAC for quality assurance, and keep TTAC as short as reasonably achievable.

The effect of time to adjuvant chemotherapy on survival in nonmetastatic resectable pancreatic adenocarcinoma: A retrospective analysis.

e14519 Background: The optimal timing for pancreatic cancer surgery to initiation of adjuvant chemotherapy (CT) is unknown. Most studies establish a maximum period of 56 days after surgery to treat patients in the adjuvant setting. We report a retrospective analysis to determine the relationship between time to adjuvant chemotherapy (TTAC) and survival. Methods: We retrospectively reviewed 29 consecutive patients with nonmetastatic resectable pancreatic adenocarcinoma who underwent curative surgery and adjuvant CT at our institution from January 2005 to December 2010. Our aim was to identify differences in PFS and OS depending on TTAC. We defined two groups of patients depending on TTAC: group A with TTAC ≤ 56 days and group B with TTAC > 56 days. Results: We identified 29 patients with resectable pancreatic adenocarcinoma who had undergone radical surgery and adjuvant CT with gemcitabine based on CONKO-001 phase III study. Nineteen were men and the median age was 61 years old (range 36-78). The median TTAC was 47 days (range 22-183). The most common reason for delaying adjuvant CT was post-operative complications. Seventeen patients initiated adjuvant CT within 56 days after surgery (group A). There were no significant statistic differences in age, gender, stage and palliative CT used at progression between the two groups. Median PFS and median OS in the whole group were 10.9 (95% CI 3.6-18.2) and 20.6 (95% CI 14.7-26.4) months respectively. Median OS was 26.4 months (95% CI 13.5-39.2) in group A and 14,8 months (95% CI 8.6-20.9) in group B. These differences were statistically significant (p value 0.015). No patient died of toxicity or post-operative complications. We could not find any significant statistic differences in median PFS between the two groups. Conclusions: This study demonstrates a higher risk of death in the group of patients who started adjuvant CT after 8 weeks of radical surgery for pancreatic adenocarcinoma. Nevertheless, no differences in PFS were found between the two groups. Theses findings indicate the need for clinicians and health systems managers to take the steps necessary to keep TTAC as short as reasonably achievable.

The impact of time to adjuvant chemotherapy (AC) on survival in colorectal cancer (CRC): A systematic review and meta-analysis.

364 Background: The optimal timing from CRC surgery to initiation of AC is unknown. We report a systematic review and meta-analysis to determine the relationship between time to adjuvant chemotherapy (TTAC) and survival. Methods: A systematic review of literature was done to identify studies that described the relationship between TTAC and survival. Studies were only included if the distribution of relevant prognostic factors was adequately described, and either comparative groups were balanced or results adjusted for the prognostic factors. Hazard ratio (HR) and TTAC for overall survival (OS) and disease free survival (DFS) from each study were converted to a regression coefficient (β) and standard error (SE) corresponding to a continuous representation per 4 weeks of TTAC. The adjusted β from individual studies were combined using a fixed-effect model. Inverse-variance (1/SE2) was used to weight individual studies. The possible effect of publication bias was investigated using the trim and fill approach. Results: We identified 9 eligible studies involving 14,357 patients (4 published articles, 5 abstracts). Two studies were randomized trials and 7 were cohort studies. Six studies reported TTAC as a binary variable and 3 reported TTAC as ≥3 categories. An estimate of HR for OS was derived from all 9 studies and estimate for DFS was derived from 5 studies. Meta-analysis demonstrated that a 4-week increase in TTAC was associated with a significant decrease in both OS (HR = 1.12, 95% CI 1.09-1.15), and DFS (HR = 1.15, 95% CI 1.11-1.20). The analysis showed no significant heterogeneity among studies. These TTAC associations remained significant after analysis for potential publication bias, and when the analysis was repeated excluding the two studies of largest weight. Conclusions: This study demonstrates a 12% increase in the risk of death for each 4 week of delay in the start of AC for CRC. These findings indicate the need for clinicians and health systems managers to take the steps necessary to keep TTAC as short as reasonably achievable. In addition, our results suggest there may be some benefit to AC after a 3-month TTAC delay. No significant financial relationships to disclose.

Does delay of adjuvant chemotherapy affect the clinical outcome in patients with colon cancer?

4046 Background: Adjuvant chemotherapy (AC) in patients with stage III colon adenocarcinoma prevents recurrences and improves survival. Although most trials mandate initiation of AC within 8 weeks of resection, the impact of timing of AC is still not clear with few studies reporting conflicting results. We hypothesized that AC commenced within 60 days of resection would increase survival in patients with stage II and III colon cancer. Methods: Patients with newly diagnosed stage II or III colon adenocarcinoma who received fluoropyrimidine based AC in two centers (a private cancer center and a large community hospital) between 2000 and 2007 were included into analysis. Time to adjuvant chemotherapy (TTC), overall survival (OS), and relapse-free survival (RFS) were calculated from the surgery date. Patients were dichotomized into early- (group 1) and late-treatment (group 2) groups using the TTC of 60 days. The demographic, clinical, and laboratory characteristics of patients in two groups were compared using chi-square and t-test. Kaplan-Meier survival curves were constructed employing univariate log-rank test to assess the effects of demographic and clinical characteristics on OS. Then the impact of TTC on OS and RFS was analyzed using a Cox proportional hazard model incorporating the significant factors found in the univariate analysis. Results: 190 patients were eligible for the study (median age: 57 yrs [range 14–84]). 116 patients (61%) were female and 35 patients (18%) had stage II disease. Median TTC was 49 days (range 24–196) and median follow-up was 143 weeks (range 9–451). 134 patients (70%) received AC within 60 days of surgery (group 1) and 56 (30%) received after (group 2). The only difference between the two groups was the higher N stage in group 1. The treating hospital and the N stage were found to be the factors affecting the OS in univariate analysis. Five-year OS for group I was 75.2% as compared to 61.3% for group II (HR 2.11, CI: 1.00–4.45, p=0.049). Five-year RFS for group I was 65.7% as compared to 59.0% for group II (HR: 1.19, CI: 0.65–2.20, p=0.570). Conclusions: Delay of AC more than 60 days after resection is associated with inferior survival in stage II/III colon cancer. No significant financial relationships to disclose.