Delay In Initiation Of Chemotherapy Research Articles

Feasibility of fertility preservation in pre-pubertal males scheduled to receive chemotherapy

Overall incidence rates of childhood cancer vary between 50-200/million children across the world. Childhood cancer survival rates are high, as are the late effects of gonadotoxic agents, such as infertility, in cancer survivors. While cryopreservation of sperm in adults is widely used, cryopreservation of testicular tissue in pre-pubertal boys has only recently been applied as a means to help preserve future fertility in pre-pubertal boys with cancer. The objective of this study is to present our experience of pre-pubertal pre-chemo fertility preservation. We reviewed all pre-pubertal patients who underwent pre-chemo fertility preservation at a large cancer center for feasibility and safety. All pre-pubertal pre-chemotherapy patients who underwent fertility preservation using testicular sperm extraction (TESE) were analyzed. Parents were informed that: the procedure was experimental, given that it is unknown if the tissue will be of use in the future; the procedure had to be performed under an anesthetic for another procedure (infusion port, bone marrow aspirates); the procedure would not be covered by insurance. A unilateral window technique was utilized as most patients were to undergo chemotherapy within 48 hours of TESE. Safety data including rates of infection, hematoma development or delay in chemotherapy initiation were recorded. A total of 22 pre-pubertal males had a mean age of 7.613 years constituted the study population. Mean FSH level was 6.9±6.3 (range 0.3-15.4) iU/ml. Most (71%) were Tanner stage 1, mean testicular volume 3.6±1.9. The most common childhood cancers in this cohort were sarcomas (55%), immune deficiencies (23%), and leukemias (14%). The procedure took an average of 22 . The tissue was sent to the sperm bank where it was cryopreserved. Viability testing on the first 10 specimens revealed healthy testicular tissue. No wound infections or scrotal hematomas occurred postoperatively. All patients were able to commence chemotherapy on schedule, usually within 24 hours or less of the fertility procedure. Fertility preservation in pre-pubertal pre-chemotherapy patients is a safe and feasible operation.

Safety and feasibility of in-hospital early chemotherapy initiation after surgery in patients with stage II-IV colon cancer.

Although it is recommended to initiate postoperative chemotherapy for colon cancer within 8 weeks after surgery, the feasibility and impact of initiating chemotherapy before discharge after surgical resection has not been investigated.Patients with stage II–IV colon cancer who received postoperative chemotherapy were dichotomized into early (chemotherapy initiation before discharge) and control (chemotherapy initiation after discharge) groups. A multivariable logistic regression model was used to determine factors associated with delayed chemotherapy, defined as more than 6 or 8 weeks after surgery.From January 2004 to December 2012, of 729 patients with stage II–IV colon adenocarcinoma, 555 patients (76.1%) underwent postoperative chemotherapy. Of them, 181 (32.6%) patients were included in the early group. Time to initiation of chemotherapy was significantly shorter in the early group than in the control group (14.9 days vs 31.5 days, P < . 001). Multivariate analysis revealed that tumor stage and chemotherapy initiation strategy (odds ratio 8.4; 95% confidence interval, 1–66, P = .041) were independent predictors of delayed initiation of chemotherapy at more than 8 weeks. There was no difference in the completion rate of planned chemotherapy cycles between the 2 groups (P > .05).The strategy of initiating chemotherapy before discharge after surgery is safe and feasible and might reduce the potential delay in chemotherapy initiation in patients with colon cancer.

Current Landscape of Targeted Therapies for Hormone-Receptor Positive, HER2 Negative Metastatic Breast Cancer.

The majority of deaths from MBC are in patients with hormone receptor (HR) positive, HER2 negative disease. Endocrine therapy (ET) remains the backbone of treatment in these cases, improving survival and quality of life. However, treatment can lose effectiveness due to primary or acquired endocrine resistance. Analysis of mechanisms of ET resistance has led to the development of a new generation of targeted therapies for advanced breast cancer. In addition to anti-estrogen therapy with selective estrogen receptor modulators, aromatase inhibitors, and/or selective estrogen receptor degraders, combinations with cyclin dependent kinase (CDK) 4/6 inhibitors have led to substantial progression free survival (PFS) improvements in the first and second line settings. While the PI3K/AKT/mTOR pathway is known to be an important growth pathway in HR positive breast cancer, PI3K inhibitors have been disappointing due to modest effect sizes and significant toxicity. The mTOR inhibitor everolimus significantly improves progression free survival when added to ET, and recent studies have improved supportive care allowing less toxicity. While these combination targeted therapies improve outcomes and often delay initiation of chemotherapy, long term overall survival data are lacking and data for the ideal strategy for sequencing these agents remains unclear. Ongoing research evaluating potential biomarkers and mechanisms of resistance is anticipated to continue to improve outcomes for patients with HR positive metastatic breast cancer. In this review, we will discuss management and ongoing challenges in the treatment of advanced HR positive, HER2 negative breast cancer, highlighting single agent and combination endocrine therapies, targeted therapies including palbociclib, ribociclib, abemaciclib, and everolimus, and sequencing of therapies in the clinic.

Risk Factors for Delays in Adjuvant Chemotherapy following Immediate Breast Reconstruction.

Concerns exist that immediate breast reconstruction may delay adjuvant chemotherapy initiation, impacting oncologic outcomes. Here, the authors determine how postoperative complications impact chemotherapy timing, and identify factors associated with greater risk for delays. Retrospective chart review identified patients undergoing immediate breast reconstruction and adjuvant chemotherapy at a single institution from 2010 to 2015. Patients were analyzed based on occurrence of postoperative complications and time to chemotherapy. A total of 182 patients (244 breast reconstructions) were included in the study; 210 (86 percent) reconstructions did not experience postoperative complications, and 34 (13.9 percent) did. Patients who experienced postoperative complications had an older mean age (53.6 years versus 48.1 years; p = 0.002) and higher rates of diabetes (23.5 percent versus 3.8 percent; p < 0.001). The complication group had delays in initiation of chemotherapy (56 versus 45 days; p = 0.017). Patients who initiated chemotherapy more than 48.5 days after reconstruction were of older mean age (55.9 years versus 50.7 years; p = 0.074) and had increased rates of diabetes (36.8 percent versus 6.7 percent; p = 0.053) and immediate autologous reconstruction (31.6 percent versus 0 percent; p = 0.027). A predictive model determined that patients with at least one of these three risk factors have a 74 percent chance of experiencing prolonged times to chemotherapy initiation. Risk factors for delayed chemotherapy in the context of postoperative complications are age older than 51.7 years, diabetes, and autologous reconstruction. Reconstructive candidates who fit this profile are at highest risk and merit extra consideration. Risk, III.

Reducing Wait Time Between Admission and Chemotherapy Initiation.

Reducing the length of stay is a high-priority objective for all health care institutions. Delays in chemotherapy initiation for planned preadmissions lead to patient dissatisfaction and prolonged length of stay. A multidisciplinary team was formed as part of the ASCO Quality Training Program. We aimed to reduce the time to initiation of chemotherapy from patient arrival at Parkland Hospital from a median of 6.2 hours at baseline to 4 hours over a 6-month period (35% reduction). The team identified inconsistency in blood work requirements, poor communication, and nonstandard patient arrival times as key causes of delay in the process. Plan-Do-Study-Act (PDSA) cycles were implemented based on identified improvement opportunities. The outcome measure was time from arrival to chemotherapy start. Data were obtained from time stamps in the electronic health record. The first PDSA cycle included patient reminders to arrive at specific times, improved communication using a smartphone secure messaging application, and preadmission notes by oncology fellows detailing whether fresh blood work were needed on admission. Baseline data from 36 patients and postimplementation data from 28 patients were analyzed. Median time from admission to chemotherapy initiation preprocess change was 6.2 hours; it was 3.2 hours postchange. A sustained shift in the process was apparent on a control chart. Delays in initiation of chemotherapy can be prevented using classic quality improvement methodology and a multidisciplinary team. We aim to further refine our PDSA cycles and ensure sustainability of change.

Implementation of Surgeon-Initiated Gene Expression Profile Testing (Onco type DX) Among Patients With Early-Stage Breast Cancer to Reduce Delays in Chemotherapy Initiation.

Delays to adjuvant chemotherapy initiation in breast cancer may adversely affect clinical outcomes and patient satisfaction. We previously identified an association between genomic testing (Onco type DX) and delayed chemotherapy initiation. We sought to reduce the interval between surgery and adjuvant chemotherapy initiation by developing standardized criteria and workflows for Onco type DX testing. Criteria for surgeon-initiated reflex Onco type DX testing, workflows for communication between surgeons and medical oncologists, and a streamlined process for receiving and processing Onco type DX requests in pathology were established by multidisciplinary consensus. Criteria for surgeon-initiated testing included patients ≤ 65 years old with T1cN0 (grade 2 or 3), T2N0 (grade 1 or 2), or T1/T2N1 (grade 1 or 2) breast cancer on final surgical pathology. Medical oncologists could elect to initiate Onco type testing for cases falling outside the criteria. We then examined 720 consecutive patients with breast cancer who underwent Onco type DX testing postoperatively between January 1, 2014 and November 28, 2016 and measured intervals between date of surgery, Onco type DX order date, result received date, and chemotherapy initiation date (if applicable) before and after intervention implementation. The introduction of standardized criteria and workflows reduced time between surgery and Onco type DX ordering, and time from surgery to receipt of result, by 7.3 days ( P < .001) and 6.3 days ( P < .001), respectively. The mean number of days between surgery and initiation of chemotherapy was also reduced by 6.4 days ( P = .004). Developing consensus on Onco type DX testing criteria and implementing streamlined workflows has led to clinically significant reductions in wait times to chemotherapy decision making and initiation.

Factors Associated With Delays in Chemotherapy Initiation Among Patients With Breast Cancer at a Comprehensive Cancer Center.

National guidelines endorse time-dependent quality metrics for breast cancer care. We examined factors associated with delays in chemotherapy initiation at an NCI-Designated Comprehensive Cancer Center. We identified 523 patients who received postoperative adjuvant chemotherapy between January 2011 and December 2013 at our center. We defined 28 days from last definitive surgery (LDS) to chemotherapy as the target time frame, and an unacceptable delay in chemotherapy initiation (UCD) as greater than 42 days from LDS. Multivariate regression models were used to identify factors associated with UCD and the impact of Oncotype DX testing in patients with hormone receptor (HR)-positive breast cancer. Median days between LDS and chemotherapy initiation was 34 (interquartile range, 15), with 30% of patients starting within 28 days of LDS and 26.9% having UCD. Tumor characteristics such as subtype and stage affected UCD; patients with HR-positive or HER2-positive tumors were more likely to be delayed compared with those with triple-negative breast cancer. Patients with stage I disease, those undergoing mastectomy with or without immediate reconstruction, and those whose pathology sign-out was greater than 10 days postoperatively were more likely to be delayed. A higher proportion of UCD was found in HR-positive patients (31%) for whom Oncotype DX testing was ordered compared with those in whom it was not ordered (20%). This study provides insight into subpopulations that may be at risk to experience delays in chemotherapy initiation, directing interventions to improve the timeliness of care.

Preoperative predictors of delay in initiation of adjuvant chemotherapy in patients undergoing primary debulking surgery for ovarian cancer

ObjectiveThe objective of this study was to identify preoperative characteristics of patients that experience a delay in initiation of adjuvant chemotherapy after primary debulking surgery for ovarian cancer. Materials/methodsWe performed a retrospective review of patients with Stage II to IV high-grade epithelial ovarian, tubal, and peritoneal carcinoma who underwent primary debulking surgery followed by adjuvant chemotherapy from 2005 to 2013. Patients were divided into 2 groups: Control (those who received their first cycle of chemotherapy within 6weeks of debulking surgery) vs. chemotherapy delay (those who received their first cycle of chemotherapy at an interval >6weeks from primary debulking surgery). Relevant clinical variables and survival outcomes were compared between the 2 groups using standard statistical methods. ResultsA total of 221 patients were included in the analyses – 169 (76.5%) were in the control group and 52 (23.5%) were in the chemo delay group. On multi-variate analysis, risk factors that were significantly associated with a delay in initiation in chemotherapy included: age >65, albumin <3.5, and high age-adjusted Charlson Comorbidity Index score. Delay in chemotherapy initiation was associated with a shorter progression-free (p=0.014) but not overall survival (p=0.19). ConclusionsDelay in initiation of chemotherapy affected 23.5% of patients in our study population. Easily identifiable risk factors for chemotherapy delay exist that can help us pre-operatively identify patients for which neoadjuvant chemotherapy may be a better treatment option. Further study into prospective modeling with these identified risk factors is warranted.

Delayed Initiation of Adjuvant Chemotherapy Among Patients With Breast Cancer.

Adjuvant chemotherapy improves outcomes of patients with breast cancer. However, the optimal timing of chemotherapy initiation is unknown. Delayed administration can decrease the benefit of cytotoxic systemic therapies. To identify the determinants in delayed chemotherapy initiation and to determine the relationship between time to chemotherapy (TTC) and outcome according to breast cancer subtype. We hypothesized that prolonged TTC would be associated with adverse outcomes. In an observational, population-based investigation using data from the California Cancer Registry, we studied a total of 24 843 patients with stage I to III invasive breast cancer diagnosed between January 1, 2005, and December 31, 2010, and treated with adjuvant chemotherapy. Data analysis was performed between August 2014 and August 2015. Time to chemotherapy was defined as the number of days between surgery and the first dose of chemotherapy, and delayed TTC was defined as 91 or more days from surgery to the first dose of adjuvant chemotherapy. We evaluated overall survival and breast cancer-specific survival. Logistic regression and Cox proportional hazard models were used. In all, 24 843 patients were included. Median age at diagnosis was 53 years, and median was TTC was 46 days. Factors associated with delays in TTC included low socioeconomic status, breast reconstruction, nonprivate insurance, and Hispanic ethnicity or non-Hispanic black race. Compared with patients receiving chemotherapy within 31 days from surgery, there was no evidence of adverse outcomes among those with TTC of 31 to 60 or 60 to 90 days. Patients treated 91 or more days from surgery experienced worse overall survival (hazard ratio [HR], 1.34; 95% CI, 1.15-1.57) and worse breast cancer-specific survival (HR, 1.27; 95% CI, 1.05-1.53). In a subgroup analysis according to subtype, longer TTC caused patients with triple-negative breast cancer to have worse overall survival (HR, 1.53; 95% CI, 1.17-2.00) and worse breast cancer-specific survival (HR, 1.53; 95% CI 1.17-2.07). For patients with breast cancer, adverse outcomes are associated with delaying initiation of adjuvant chemotherapy 91 or more days. Delayed TTC was particularly detrimental among patients with triple-negative breast cancer. The determinants of delays in chemotherapy initiation appeared to be sociodemographic, and clinicians should provide timelier care to all patients.

Abstract P1-12-08: Factors associated with delays in chemotherapy initiation among patients with breast cancer

Abstract Background: National guidelines endorse time-dependent quality metrics for breast cancer care. We examined factors associated with delays in chemotherapy initiation at an NCI designated comprehensive cancer center. Methods: We identified 523 patients who received post-operative adjuvant chemotherapy between January 2011 and December 2013 at our center. We defined 28 days from last definitive surgery (LDS) to chemotherapy as the target timeframe, and unacceptable delay in chemotherapy initiation (UCD) as more than 42 days from LDS. Multivariate regression models were used to identify factors associated with UCD and the impact of Oncotype testing in HR+ patients. Results: Median days between LDS and chemotherapy initiation was 34 (IQR 15), with 30% of patients starting within 28 days of LDS and 23% having UCD (Table 1). Tumor characteristics such as subtype and stage affected UCD; patients with HR+ or HER2+ tumors were more likely to be delayed compared to those with TNBC. Patients with stage I disease were more likely to be delayed as well as patients undergoing mastectomy or mastectomy with reconstruction. Patients whose pathology sign-out was more than 10 days post-operatively were more likely to be delayed. A higher proportion of UCD was found in HR+ patients (31%) who received an Oncotype recurrence score compared to those who did not (20%). Table 1: Factors associated with delays in chemotherapy initiation N% DelayOdds Ratio95% CITotal52323 Age&amp;lt;4068191.00.5-2.340 to 49165161.0--50 to 59150252.01.1-3.660 to 69113282.51.3-5.070+27374.11.4-12.3RaceWhite424221.0--Non-White79271.50.8-2.7Missing20251.10.4-3.3InsurancePrivate419211.0--Public104321.60.8-2.9StageI208211.0--II243281.30.8-2.1III72110.30.1-0.7Tumor SubtypeHER2-/HR-105151.0--HR+HER2-264242.11.1-4.2HER2+154272.01.0-3.9Surgery TypeLumpectomy265161.0--Mastectomy89292.51.3-4.5Mastectomy with Immediate Reconstruction169313.31.9-5.6Pathology Sign-Out (&amp;gt;10 days)No331191.0--Yes192322.01.3-3.2Post-Op ComplicationsNo506221.0--Yes17412.20.7-6.6Clinical trial considerationNo435231.0--Yes88240.90.5-17 Conclusions: This study provides insight into populations that may be at risk to experience delays in chemotherapy initiation, directing interventions to improve the timeliness of care. Citation Format: Losk K, Vaz Duarte Luis I, Camuso K, Lloyd M, Kadish S, Hirshfield-Bartek J, Cutone L, Golshan M, Lin N, Bunnell C. Factors associated with delays in chemotherapy initiation among patients with breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-12-08.

Abstract P1-12-07: Delayed initiation of adjuvant chemotherapy among breast cancer patients: A population-based study

Abstract BACKGROUND: Adjuvant chemotherapy improves outcomes of breast cancer patients; however the optimal timing to initiation of chemotherapy remains unknown. No study has evaluated the relationship between time to chemotherapy (TTC) and outcome in a population-based study of patients treated with contemporary regimens according to tumor subtype. In this large study we identified the determinants associated with a delay in the initiation of chemotherapy and determined whether TTC is related to outcome. METHODS: Breast cancer patients diagnosed with stage I-III breast cancer between 2005-2010 and treated with adjuvant chemotherapy were identified in the California Cancer Registry. TTC was defined as number of days between surgery and the day the first dose of adjuvant chemotherapy was administered. Delayed TTC was defined as &amp;gt;91 days. Logistic regression and Cox-proportional hazard modeling were used. RESULTS: A total of 24,843 patients were included. Factors associated with delays in TTC included low socioeconomic status, reconstructive surgical procedure, non-private insurance and Hispanic or non-Hispanic black race/ethnicity. Compared to patients receiving chemotherapy within 31 days from surgery, there was no evidence of adverse outcome among those with TTC of 31-60 or 60-90 days. To the contrary, patients treated &amp;gt;91 days from surgery experienced statistically significant worse overall survival (OS) (HR=1.34; 95%CI 1.15-1.57) and worse breast cancer specific survival (BCSS) (HR=1.27; 95%CI 1.05-1.53). In a subgroup analysis according to breast cancer subtype, TTC &amp;gt;91 days had a statistically significant detrimental impact among patients with triple negative breast cancer (TNBC) in terms of both OS (HR=1.53; 95%CI 1.17-2.00) and BCSS (HR=1.53; 95%CI 1.17-2.07). CONCLUSIONS: In this large cohort of breast cancer patients treated with contemporary regimens, a delaying in the initiation of adjuvant chemotherapy &amp;gt;91 days was associated with adverse outcomes. A delay in TTC is particularly detrimental among patients with TNBC. The majority of the determinants of delays in chemotherapy initiation are socio-demographic in nature. As medical providers we must make every effort to provide timely care to all our patients so they can receive the full benefit of our current treatments. Citation Format: Chavez-MacGregor M, Clark CA, Lichetensztajn DY, Giordano SH. Delayed initiation of adjuvant chemotherapy among breast cancer patients: A population-based study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-12-07.

Time from Hospital Admission to Induction Chemotherapy Adversely Affects Outcomes in Patients with Acute Myeloid Leukemia

Background:The duration of time from the diagnosis of acute myeloid leukemia (AML) to the initiation of chemotherapy is dependent on multiple factors. Previous studies suggest that delays in the time from diagnosis to treatment do not impact overall survival (OS) and complete remission (CR). As a result, awaiting laboratory analysis of molecular targets for therapy, specifically FLT3, has become more commonly adopted by clinicians. However, this strategy can lead to significant delays in initiation of chemotherapy. The aim of this study is to analyze the impact of delaying chemotherapy on OS and CR in AML patients.Methods:We performed a retrospective analysis on adult patients with AML who were treated with induction chemotherapy at The University of Oklahoma Health Sciences Center from January 2000 to June 2012. Time from admission to treatment (TAT) was calculated from the date of admission to the date of initiation of chemotherapy. In addition, we analyzed the admission day of the week and its association with TAT (days). Association between CR and TAT was assessed using ANOVA and Chi-Square tests. Kaplan-Meier estimates of median OS were calculated for groups defined by categorical variables. A Cox Proportional Hazards model on OS was implemented using TAT, age, risk status (favorable, intermediate and unfavorable risks), day of admission, distance to hospital, and white blood cell (WBC) count. Interaction was assessed and a backward selection procedure was used to find the covariates associated with OS. Statistical analysis was performed using SAS 9.3 software.Results:A total of 160 patients with AML received induction chemotherapy at our institution during the defined time, with 137 meeting inclusion criteria. The median age at diagnosis was 51 years with 63.7% being male and 36.3% being female. Of these patients, 77.0% were white, 10.6% African American, 6.2% Native American and 3.7% Hispanic. The median TAT for all patients was 3.0 days. There were 116 (84.7%) patients treated within 0-4 days (Group 1) and 21 (15.3%) patients treated beyond 4 days (Group 2). Patients in Group 1 had a median survival of 252.5 days compared to those in Group 2 of 188.5 days (p = 0.0958) when analyzed univariately. Multivariable analysis demonstrated TAT of 0-4 days was independently related to OS with a hazard ratio of .604 (95% CI 0.369-0.990, p = 0.0451). The CR rate for Group 1 was 69.8% compared to Group 2 of 54.6% (p = 0.0692). In addition, patients admitted on a weekday (Monday-Friday) were more likely to initiate chemotherapy within 0-4 days as compared to patients admitted on the weekend (Saturday-Sunday) with a p = 0.0102.Conclusion:AML patients treated more than 4 days following admission have decreased OS and a trend toward decreased rate of CR as compared to patients treated within 0-4 days. This finding is independent of age, risk status, WBC count, and distance to hospital. Also, patients admitted on the weekend were more likely to experience delays in initiating chemotherapy compared to those admitted on the weekday. Although a larger sample size and testing in other clinic settings needs to be done to confirm this relationship, this study suggests treating AML patients within 4 days of hospital admission may be associated with improved outcomes. DisclosuresNo relevant conflicts of interest to declare.

The impact of delayed chemotherapy on its completion and survival outcomes in stage II colon cancer patients.

BackgroundDelayed chemotherapy is associated with inferior survival in stage III colon and stage II/III rectal cancer patients, but similar studies have not been performed in stage II colon cancer patients. We investigate the association between delayed and incomplete chemotherapy, and the association of delayed chemotherapy with survival in stage II colon cancer patients.Patients and MethodsPatients (age ≥66) diagnosed as stage II colon cancer and received chemotherapy from 1992 to 2005 were identified from the linked SEER–Medicare database. The association between delayed and incomplete chemotherapy was assessed using unconditional and conditional logistic regressions. Survival outcomes were assessed using stratified Cox regression based on propensity score matched samples.Results4,209 stage II colon cancer patients were included, of whom 73.0% had chemotherapy initiated timely (≤2 months after surgery), 14.7% had chemotherapy initiated with moderate delay (2–3 months), and 12.3% had delayed chemotherapy (≥3 months). Delayed chemotherapy was associated with not completing chemotherapy (adjusted odds ratio (OR): 1.33 (95% confidence interval: 1.11, 1.59) for moderately delayed group, adjusted OR: 2.60 (2.09, 3.24) for delayed group). Delayed chemotherapy was associated with worse survival outcomes (hazard ratio (HR): 1.75 (1.29, 2.37) for overall survival; HR: 4.23 (2.19, 8.20) for cancer-specific survival).ConclusionAlthough the benefit of chemotherapy is unclear in stage II colon cancer patients, delay in initiation of chemotherapy is associated with an incomplete chemotherapy course and poorer survival, especially cancer-specific survival. Causal inference in the association between delayed initiation of chemotherapy and inferior survival requires further investigation.

Mo1072 Optimizing the Utilization of Adjuvant Chemotherapy Following Surgical Resection of Colon Cancer: A Comparison of Laparoscopic Versus Open Approach

Purpose Previous research has demonstrated that laparoscopic approach to colon cancer resection is a safe and potentially beneficial alternative to open surgery. Open colon cancer surgery has higher complication rates than laparoscopic surgery, whichmay delay chemotherapy for stage-specific tumors. Omission or delay in chemotherapy is known to significantly impact overall survival. In this study, we examine the use of appropriate adjuvant chemotherapy following open and laparoscopic surgery for colon cancer in a large national cancer registry. Methods The National Cancer Data Base (NCDB) captures over 70% of cancer cases in the United States and provides detailed information on patient, tumor, and treatment characteristics. Cases of colon cancer undergoing segmental or hemicolectomy with node positive disease in the NCDB from 2010-2011 were included in the analysis. Primary outcomes were use of any adjuvant chemotherapy and use of adjuvant chemotherapy within 90 days of surgery. To adjust for non-random treatment selection, propensity adjustment with inverse probability weighting (IPW) was performed. Patient and tumor characteristics before and after IPW adjustment were compared. Weighted logistic regression after IPW was used to compare the association of laparoscopic and open surgery with the use of adjuvant chemotherapy. Results From 2010-2011, 19,531 patients with colon cancer and positive lymph nodes undergoing surgery were identified in the NCDB, with 12,088 patients (61.9%) undergoing open surgery and 7,443 (38.1%) treated laparoscopically. Patients undergoing open surgery tended to have more comorbidities, larger tumors, higher clinical T and N staging, and were more likely to be treated at community cancer programs (as opposed to comprehensive cancer centers or academic research programs); however, these differences were minimized after IPW adjustment (Table). Before IPW, rates of adjuvant chemotherapy use were 62.3% for patients after open surgical resection, compared to 70.6% after laparoscopic surgery (p<0.001). After IPW, odds ratio (OR) for adjuvant chemotherapy use was 1.27 (95% CI: 1.19-1.36) for laparoscopic versus open surgery, indicating that patients undergoing laparoscopic surgery were more likely to receive adjuvant therapy. For adjuvant chemotherapy within 90 days of surgery, OR was 1.28 (1.20-1.36), again favoring a laparoscopic approach (Figure). Conclusion Patients undergoing laparoscopic surgery for pathologic stage III colon cancer had higher rates of adjuvant chemotherapy use and lower rates of delay in chemotherapy initiation compared to those treated with open procedures, likely due to reduced complications from laparoscopic surgery. Further research will need to examine long-term outcomes in this population in order to understand the impact on disease recurrence and long-term survival. Table. Preoperative patient characteristics by surgical approach before and after IPW adjustment

Time from diagnosis to intensive chemotherapy initiation does not adversely impact the outcome of patients with acute myeloid leukemia

AbstractIn acute myeloid leukemia (AML), new strategies assess the potential benefit of genetically targeted therapy at diagnosis. This implies waiting for laboratory tests and therefore a delay in initiation of chemotherapy. We studied the impact of time from diagnosis to treatment (TDT) on overall survival, early death, and response rate in a retrospective series of 599 newly diagnosed AML patients treated by induction chemotherapy between 2000 and 2009. The effect of TDT was assessed using multivariate analysis. TDT was analyzed as a continuous variable using a specific polynomial function to model the shape and form of the relationship. The median TDT was 8 days (interquartile range, 4-16) and was significantly longer in patients with a white blood cell count (WBC) <50 Giga per liter (G/L) (P < .0001) and in older patients (P = .0004). In multivariate analysis, TDT had no impact on overall survival (P = .4095) compared with age >60 years, secondary AML, WBC >50 G/L, European LeukemiaNet risk groups, and Eastern Cooperative Oncology Group performance status. Furthermore, TDT was not associated with response rate and early death. Thus, waiting a short period of time for laboratory tests to characterize leukemias better and design adapted therapeutic strategies at diagnosis seems possible.

WS3-5 - Practice and Problems in Conducting HER2-Testing and Trastuzumab-Combined Chemotherapy for Advanced/Recurrent Gastric Cancer

ABSTRACT Background Approval of trastuzumab (Her) following ToGA trial was a milestone of chemotherapy for advanced/recurrent gastric cancer. In this presentation, we report the practice, in Kyushu Cancer Center, of HER2 screening, safety and efficacy of Her-combined chemotherapy, and discuss on the problems of clinical practice. Methods We examined HER2-immunohistochemistry (IHC) on 90 cases of advanced/recurrent gastric cancer which were under chemotherapy on March 2011 or initiated chemotherapy until January 2012 at Kyushu Cancer Center. HER2 fluorescent in situ hibridization (FISH) was tested when IHC result was 2+. Her-combined chemotherapy was planned to HER2-high cases (IHC 3+ or IHC2+ and FISH positive). Results IHC results of 90 cases were 3 + : 12, 2 + : 6, 1 + : 11 and 0: 61 cases, respectively. Five positive FISH results were obtained out of six IHC 2+ cases. We experienced 17 HER2-high cases (18.9%). Her-combined chemotherapy was planned as first-line therapy (11 cases) or subsequent lines (3 cases), gaining 6 PR. Only three cases were started initial therapy as Her-combined, and others were started with chemotherapy alone and added Her later. As adverse events, three infusion reactions and no cardiac toxicity was observed. Conclusions An equivalent HER2-high rate as previous reports was observed in our practice. Many cases did not allow delay in initiation of chemotherapy during HER2 testing, and chemotherapy was often started without HER2 results. Further practical experiences and new evidences were needed in the point of chemotherapy initiation. Her-combined chemotherapy was safely carried out, and its efficacy must be confirmed by further accumulation of trials and practical experiences.

“Watchful waiting” for metastatic colorectal cancer, antediluvian or an option to be considered again?

The role of chemotherapy in metastatic colorectal cancer (mCRC) is firmly established and the option of watchful waiting (WW) has become an alternative rarely considered. However, there may be a group of patients who are diagnosed with low volume and asymptomatic disease and who may be suitable for a WW plan. From the South Australian Cancer Registry for mCRC we examined cancer characteristics and outcomes of patients who were suitable for chemotherapy but had their treatment delayed by more than 3 months from diagnosis of metastatic disease. Data from 417 mCRC patients who received chemotherapy as first intervention have been entered in the Registry to date and 38 (9.1%) had chemotherapy commencement delayed by more than 3 months from diagnosis. Their median age was 76.7 years (range 38-85). Overall 87% of patients had metachronous metastatic cancer with a median time to recurrence of 2.1 years (range 0.53-7.71) and 65.5% had single organ metastasis. Median delay from the diagnosis of metastatic disease to chemotherapy was 5.03 months (range 3-28). The median survival has yet to be reached. The 2-year overall survival is 65%. We found that almost 10% of all patients with mCRC had a delay in the initiation of chemotherapy, with most due to a WW approach based on case note review. Patients with a delay in chemotherapy initiation are more likely to have a single organ site of metastatic disease and are older than those who do not. Despite the treatment delay, there is no evidence of a negative impact on survival.

Effect of Postoperative Complications on Survival of Patients Treated for Rectal Cancer

Introduction: Rectal cancer is a common and lethal disease. Surgical resection after chemoradiation remains the standard of care, and is followed by adjuvant chemotherapy in patients at high risk for recurrence. the rate of complications following surgery for rectal cancer remains unacceptably high. We wanted to evaluate the effect of complications on overall survival. We hypothesized that delay in initiation of chemotherapy following surgery for rectal cancer negatively impacts survival. Methods: From 1995-2010, 301 patients underwent surgical resection of rectal cancer at our institution.

Weekend Delay in Initiation of Chemotherapy for Acute Lymphoblastic Leukemia

The Friday afternoon admission of a child with a potential diagnosis of leukemia creates perceived delays in treatment initiation. Although generally not felt to affect prognosis, the effect of a few days delay in chemotherapy for children with acute lymphoblastic leukemia (ALL) has not been fully investigated. We retrospectively analyzed 207 patients consecutively diagnosed with ALL at Children's Hospital & Research Center Oakland from 1995 to 2007 to determine if delay in chemotherapy increased the risk of relapse, death, transfer to the intensive care unit, or bacteremia. Friday admission did not significantly delay chemotherapy initiation with treatment started at a mean of 4.13±2.40 days for Friday admits versus 3.72±1.57 days for all others (P=0.29). There was no significant association between treatment delay days and relapse (P=0.94) or death (P=0.55). In Cox regression analysis, treatment delay was not a predictor of time to relapse (P=0.80) or longer duration of hospitalization (corrected for delay, P=0.15). There were trends toward significant associations between treatment delay and bacteremia (P=0.07) and intensive care unit admissions (P=0.08), although both were associated with shorter, not longer, treatment delays.We were unable to demonstrate a significant effect of delay in chemotherapy initiation for pediatric patients with newly diagnosed ALL on the examined outcome variables.

Chimiothérapie et préservation de la fertilité féminine

Agressive chemotherapy can lead to premature ovarian failure and loss of fertility in women and children. Embryo cryopreservation is an established clinical procedure of fertility preservation but with several limitations. Others options are available. Cryopreservation ovarian cortex tissu have to be suggested in case of high gonadotoxic treatment. It doesn't require puberty and delay in initiation of chemotherapy. The first birth in France after orthotopic graft of ovarian tissu thawed have been recently described with a promising process. Oocyte cryopreservation is available for women without partner but the experience is limited. Gonadotrophin-releasing hormone (GnRH) agonist therapy as ovarian protectants seem interesting. Follicular growth and maturation in vitro are still experimental.