Utilization Of Adjuvant Therapy Research Articles

Adjuvant Therapy for Node Positive Esophageal Cancer at Surgery Does Not Improve Survival

Background: The current standard of care for the management of node positive (N) esophageal cancer is induction chemoradiation therapy followed by definite surgical therapy. The utility of adjuvant therapy in patients with persistent histologic evidence of N1 disease post resection is unclear. In this study, we compare survival rates in patients with postsurgical N disease who undergo adjuvant vs. no further therapy. Methods: Using an IRB-approved endoscopic ultrasound (EUS) database, we conducted a retrospective analysis of 77 patients (62 males, 15 females, mean age 60. 4 ± 9.9 years) with esophageal cancer and node positive (N) disease on EUS from2003 to 2010who subsequently underwent surgical resection. Outcomes of patients with surgical node-positive disease undergoing no further therapy were compared to those who underwent adjuvant therapy in terms of significant morbidity (as determined by hospital admissions) and mortality. Results: After neoadjuvant down-staging, a subgroup analysis of the 50 patients with persistent node positive disease on surgical specimen at esophagectomy was carried out. Of the 50 patients, 22 (44%) underwent adjuvant therapy, 24 (48%) did not undergo further chemotherapy and 4 (8%) were lost to follow-up. Morbidity rates were: 11/22 (50%) for those who underwent adjuvant chemotherapy and 7/24 (29%) for those who did not receive adjuvant therapy (p = 0.23, Fisher's Exact Test). Mortality rates were: 10/22 (45%) for those who underwent adjuvant chemotherapy and 13/24 (54%) for those who did not receive adjuvant therapy (p=0.77, Fisher's Exact Test). A KaplanMeier survival curve comparing adjuvant versus no post-operative therapy demonstrated no survival difference (p=0.83) (Figure 1). Conclusion: The addition of adjuvant therapy to surgical node-positive esophageal cancer did not confer a survival advantage. Morbidity was noted to be higher in the adjuvant therapy group however given the small numbers was not statistically significant. Further study into adjuvant therapy for node positive surgical disease is warranted.

Adjuvant medical therapy for prostate cancer

Importance of the field: Prostate cancer is a common cancer and the role of adjuvant medical therapy continues to be investigated. An understanding of the use of adjuvant medical therapy is essential for the appropriate care of prostate cancer patients, especially for those with locally advanced or high-risk disease.Areas covered in this review: This article reviews the role of adjuvant treatment of non-metastatic prostate cancer. To identify all pertinent publications, a literature search of the National Library of Medicine (PubMed) from inception to 22 June 2010 was conducted for ‘adjuvant prostate cancer’, with these results filtered for clinical trials and systematic reviews.What the reader will gain: This work reviews the uses of adjuvant androgen deprivation therapy and chemotherapy for prostate cancer. There is a clear benefit from the use of androgen deprivation therapy in conjunction with radiation therapy for selected patients, but the role of postoperative chemotherapy is poorly defined. Identifying appropriate patients for adjuvant therapy continues to be a challenge.Take home message: There is a complex literature describing the role of adjuvant medical therapy in prostate cancer, which is reviewed here. Continuing and future clinical trials will define the utility of adjuvant therapy in this setting and require the support of the clinical community.

Utilization of adjuvant therapy among completely resected non-small cell lung cancer (NSCLC) patients in the National Comprehensive Cancer Network (NCCN) Outcomes Database Project.

7017 Background: In recent years, adjuvant chemotherapy has become the standard of care for completely resected (R0) stage II and IIIA NSCLC patients, while the use of adjuvant therapy in stage IB remains controversial. We evaluated the use of adjuvant therapy among R0 stage IA-IIIA NSCLC patients in the NCCN Outcomes Database Project. Methods: Completely resected stage I-IIIA NSCLC patients who did not receive preoperative therapy were selected for analysis. Eligible patients received adjuvant treatment at 8 participating NCCN institutions between 01/2007 and 06/2009 and were at least 90 days postsurgery. Adjuvant therapy was defined as therapy initiated within 3 months of surgery. Analyses were done on 12/11/09. Results: A total of 498 patients met the inclusion criteria. Patient characteristics were: male 42%; median age 67 yrs; stage IA 39%, IB 35%, II 16%, IIIA 10%; lobectomy (uni or bi) 84% (N=416); adenocarcinoma 58% (N=289); performance status (PS) 0-1 54% (N=271), PS ≥2 3% (N=16), and undocumented PS 42% (N=211). Adjuvant treatment category is presented by stage in the Table. Of patients receiving adjuvant therapy, 5 (4%) did so on a clinical trial. The most common reason for not receiving adjuvant systemic therapy in stage II-IIIA was patient refusal (26%). Conclusions: Adjuvant therapy was commonly administered to stage II and IIIA patients. Radiation was most common among stage IIIA patients. While the majority of R0 NSCLC patients received treatment that follows NCCN guidelines, relatively few patients at these NCCN centers are participating in clinical trials. Adjuvant treatment category by stage Treatment category Stage IA (N=193) IB (N=174) II (N=79) IIIA (N=52) No treatment 190 (98%) 126 (72%) 25 (32%) 14 (27%) Chemotherapy 2 (1%) 43 (25%) 43 (54%) 20 (38%) Cisplatin-based 2 (100%) 25 (58%) 25 (58%) 10 (50%) Carboplatin-based 0 (0%) 14 (33%) 17 (40%) 8 (40%) Other 0 (0%) 4 (9%) 1 (2%) 2 (10%) Chemotherapy + targeted therapy 0 (0%) 2 (1%) 0 (0%) 0 (0%) Targeted therapy alone 0 (0%) 2 (1%) 2 (3%) 1 (2%) Sequential chemo/RT 1 (<1%) 0 (0%) 6 (8%) 13 (25%) Concurrent chemo/RT 0 (0%) 0 (0%) 1 (1%) 3 (6%) RT alone 0 (0%) 1 (<1%) 2 (3%) 1 (2%) Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abraxis BioScience

Impact of Selection Bias on the Utilization of Adjuvant Therapy for Pancreas Adenocarcinoma

Improved outcomes have been associated with the use of adjuvant therapy after resection of pancreas adenocarcinoma. However, the frequency with which patients receive adjuvant therapy and the factors impacting its use remain largely undefined. We hypothesized that nonutilization of adjuvant therapy was primarily associated with patient comorbidity and onset of postoperative complications. A prospectively maintained database was reviewed to identify patients who underwent potentially curative resection of histologically confirmed pancreas adenocarcinoma at our institution from January 1996 to May 2007. Clinicopathological data and postoperative treatment history were collected to identify variables associated with receipt of adjuvant therapy. Of 119 patients, 33% did not receive adjuvant therapy. The frequency with which patients underwent adjuvant therapy did not change over time. On multivariate analysis, patient age 70 years or greater, major postoperative complications, distal pancreatectomy, absence of nodal metastases, and absence of perineural invasion were associated with decreased utilization of adjuvant therapy. One-third of patients in this contemporary dataset of patients did not go on to receive adjuvant therapy. The likelihood of receiving adjuvant treatment is negatively impacted by the course of postoperative recovery. Moreover, the fact that adjuvant therapy was undertaken less often for older patients and patients with favorable pathological features highlights the selection bias impacting the decision to pursue postoperative therapy for this disease. This selective utilization of postoperative therapy for patients with adverse oncological characteristics is likely to bias any retrospective analysis attempting to measure the efficacy of adjuvant treatment for pancreas adenocarcinoma.

Intracranial tumors in first year of life: the CHEO experience

One seventh of pediatric brain tumors are diagnosed in the first year of life. With more widespread and accessible neuroimaging, these lesions are being diagnosed earlier, but there remains scant literature about their natural history. A retrospective review was performed of brain tumor patients presenting to the Children's Hospital of Eastern Ontario (CHEO) through the last 34 years. Patients presenting in the first year of life, including symptoms, management features, and functional outcome, were analyzed using ANOVA and chi (2) statistics. Eighteen cases of brain tumors in the first year of life were identified: 12 suptratentorial, eight with benign histology, and six infratentorial all with malignant histology. Median age of presentation differed by lesion location (p = 0.05) and glial tumors were most common. Raised intracranial pressure was more than twice as prevalent with posterior fossa lesions (p < 0.01) with equivalent likelihood of increasing head circumference (p = 0.74), whereas seizures were more frequent with supratentorial tumors (p = 0.04). Gross total resection was achieved in 47% of patients, cerebrospinal fluid diversion was more frequently necessary among infratentorial lesions (p = 0.02), and adjuvant therapy was more utilized for infratentorial lesions (p < 0.01). Among eight surviving infants, seven had supratentorial tumors, five survived to adulthood, and six are functionally independent. Brain tumors in the first year of life represent 4.8% of patients treated at CHEO. Mode of presentation, utilization of adjuvant therapy, and survival depend on tumor location and histology, with worse prognosis for infratentorial lesions. One third of patients had acceptable functional outcome requiring no special assistance.

A population based analysis of surgical and adjuvant therapy for resectable gastric adenocarcinoma

6596 Background: The utilization of adjuvant therapy after resection for gastric adenocarcinoma has become standard of care since the publication of the Intergroup 0116 data. The resection of at least 15 lymph nodes (LN) has been shown to improve staging accuracy. The aims of this study were: 1) to assess current practice patterns in the treatment of gastric cancer, 2) to determine the association between the use of chemoradiotherapy (CRT) and patient survival. Methods: Data from the Oregon State Cancer Registry were abstracted for demographics, disease stage, resection type, number of LNs resected, adjuvant CRT, and survival for the years 1996–2006. Only patients with resection for stage IB-III disease were selected for analysis. Patients were divided into those who received treatment through year 2001 (group 1) and after 2001 (group 2). The x2 test was used to compare the application of CRT between groups. Number of LNs sampled was evaluated with the Mann-Whitney U test. Univariate and multivariate analyses of survival were performed with the Kaplan-Meier log-rank test and the Cox proportional hazards model. Results: There were 313 patients who met study criteria. Adjuvant therapy was employed in 14.2% of cases in group 1 vs 33.3% in group 2 (p<0.001). The median number of LNs sampled in group 1 was 10 compared to 11 in group 2 (p=0.026). Thirty-five percent of patients had at least 15 nodes sampled irrespective of resection type. Survival analysis demonstrated a 5 month median survival advantage for patients that received CRT (Table). Conclusions: Although the proportion of patients who received adjuvant CRT increased after publication of Intergroup 0116 data, 66% of patients that were eligible did not receive CRT. Patients who received stage-appropriate adjuvant therapy demonstrated a trend toward improved survival. The number of LNs sampled did not appear to influence survival. Future efforts should focus on removing barriers to the receipt of adjuvant therapy following resection of gastric adenocarcinoma. Survival analysis for patients with resectable gastric adenocarcinoma Category Median Survival (months) P value Univariate P value Multivariate Hazard Ratio (95% CI) T Stage - 0.027 0.011 NA T1 47 NA NA T2 23 0.068 2.67 (0.93–7.67) T3 13 0.012 3.80 (1.34–10.77) T4 16 0.010 4.67 (1.45–15.00) N Stage - 0.071 0.020 NA N0 21 NA NA N1 16 0.008 1.64 (1.14–2.37) N2 13 0.038 1.59 (1.03–2.45) >15 Nodes Sampled - 0.868 0.738 0.94 (0.67–1.33) No 17 Yes 17 CRT - 0.300 0.099 0.71 (0.48–1.07) No 15 Yes 20 CRT, chemoradiotherapy; CI, confidence interval No significant financial relationships to disclose.

An Aggressive Approach to Extrahepatic Cholangiocarcinomas Is Warranted: Margin Status Does Not Impact Survival after Resection

With cholangiocarcinoma, the only hope of a cure is resection. This study was undertaken to determine the impact of margin status, stage, tumor location, and adjuvant therapy on survival after resection of extrahepatic cholangiocarcinoma. From 1985-2006, 91 patients underwent resections of cholangiocarcinomas. Margin status was codified as micro-/macroscopically negative, microscopically positive/ macroscopically negative, or micro-/macroscopically positive. Stage was determined using the AJCC classification (6th edition). Tumor location was classified as proximal, mid, or distal. Proximal tumors were resected by extrahepatic biliary resection with/without concomitant hepatic resection (n = 48), distal extrahepatic cholangiocarcinomas by pancreaticoduodenectomy (n = 35), and mid tumors by extrahepatic biliary resection alone (n = 8). Regression analysis and survival curve analysis were utilized. Data are presented as median, mean +/- standard deviation (SD). Overall survival after resection was 21 months, 38 +/- 46.0. Survival was not impacted by margin status (R0 20 months, 35 +/- 45.1 versus R1 32 months, 45 +/- 49.4). AJCC stage inversely correlated with survival (p = 0.004, Spearman regression analysis). Tumor location did not impact upon survival (p = 0.57, log-rank test). For proximal tumors, survival after biliary resection was significantly impacted by the need for concomitant hepatectomy (15 months, 27 +/- 31.4 versus 41 months, 67 +/- 17.1). Utilization of adjuvant therapy significantly improved survival (33 months, 56 +/- 63.1 versus 19 months, 33 +/- 40.0) (p = 0.046, Spearman regression). Survival after resection of extrahepatic cholangiocarcinoma is significantly impacted by AJCC stage, the use of adjuvant therapy, and in patients with proximal tumors, the need for concomitant hepatectomy. Margin status and tumor location do not impact survival. Cholangiocarcinomas should be aggressively resected irrespective of tumor location, even if resection might result in microscopically positive margins, and adjuvant therapy applied.

Chapter 2: Dissemination of Adjuvant Multiagent Chemotherapy and Tamoxifen for Breast Cancer in the United States Using Estrogen Receptor Information: 1975-1999

Clinical trials have shown tamoxifen to be effective only in women with estrogen receptor (ER)-positive tumors. In a previous model, trends in the utilization of adjuvant therapy were modeled only as a function of age and stage of the disease and not ER status. In this paper, we integrate this previous estimate on the use of adjuvant systemic therapy for breast cancer in the United States with information on ER status from the Patterns of Care (POC) data to estimate the dissemination of adjuvant therapy for women with different ER-status tumors. We also summarize efficacy of adjuvant systemic therapy reported in the overviews of early breast cancer clinical trials. These two inputs, dissemination and efficacy, are key pieces for models that investigate the effect of breast cancer adjuvant therapy on the decline of U.S. breast cancer mortality. The adjustments to the previous models are calculated using the POC data on 7116 women with breast cancer diagnosed from 1987 to 1991 and in 1995 who were randomly selected from the Surveillance, and Epidemiology, and End Results (SEER) program registries. The POC data provide more accurate information on treatment and clinical variables (e.g., ER status) than the SEER data because medical records are reabstracted and further verified with treating physicians. Use of multiagent chemotherapy is higher for younger women (<50 years) and for women whose tumors were shown to be ER negative or borderline. The use of tamoxifen is higher among older women and women with ER-positive tumors. After 1980 the combined use of multiagent chemotherapy and tamoxifen for women diagnosed with breast cancer at ages 69 or younger increased more for women whose tumors were ER status positive or unknown than ER status negative. Older women (>69 years) seem to receive almost exclusively tamoxifen irrespective of ER status, except for a small percentage of those with more advanced stages (II- and II+/IIIA) who also receive multiagent chemotherapy. The estimated dissemination trends by ER status, based on modeling the POC data, reveal that treatment strategies with demonstrated efficacy in clinical trials have been adopted into practice. The dissemination and efficacy are the two factors necessary to input into models to determine the population impact of these therapies on U.S. breast cancer mortality. The largest decline in mortality would be expected for younger women (<60 years) with ER-positive tumors or whose tumors are of unknown status because of the largest efficacy and dissemination of adjuvant therapy in this group.

Appropriate Utilization of Adjuvant Therapy Following Colorectal Cancer Diagnosis

Appropriate Utilization of Adjuvant Therapy Following Colorectal Cancer Diagnosis