Adjuvant chemoradiation for node-positive pancreatic adenocarcinoma: A propensity-matched analysis.

347 Background: American Society of Clinical Oncology guidelines recommend adjuvant chemoradiation (ACR) for margin-positive(R1) and/or node-positive (N+) pancreatic cancers. However, randomized trials and meta-analyses have have not shown superiority of ACR over AC. Methods: National Cancer Database (NCDB) was used to analyze patients with N+ and/or R1 pancreatic adenocarcinoma who underwent ACR or AC over a ten-year period (2004-2014). Patients who received neoadjuvant radiation, no adjuvant treatment or adjuvant radiation alone were excluded. Propensity score nearest-neighbor 1:1 matching (PSM) was performed between ACR and AC groups based on age, sex, race, insurance, comorbidities, T-stage, nodal status, margin status, grade, and neoadjuvant chemotherapy. Primary outcome was overall survival (OS). Results: A total of 9,732 patients were eligible. After PSM two well-balanced groups of 4000 patients each were analyzed. ACR resulted in superior OS in patients with N+ and/or R1 disease as compared to AC alone (HR: 0.83, 95% CI 0.78-0.87; Median OS 22 vs. 19 months, p<0.001). Subset analyses demonstrated overall survival benefit of ACR compared to AC in N+, margin-negative patients (HR: 0.82, 95% CI 0.77-0.88; Median OS 24 vs. 20 months, p<0.001), as well as N+, R1 patients (HR: 0.77, 95% CI 0.68-0.87; Median OS 17 vs. 15 months, p<0.001); but no benefit in node-negative, R1 patients (HR: 1.12, 95% CI 0.84-1.48; Median OS 18 vs. 22 months, p = 0.43). Conclusions: This is the largest study to date that shows superiority of ACR over AC in N+ patients irrespective of margin status. The study failed to show a survival benefit in R1, node-negative patients.

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Association of adjuvant chemotherapy with overall survival in resected pancreatic adenocarcinoma previously treated with neoadjuvant therapy.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.404 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 404-404 ◽

Cited By ~ 1

Author(s):

Douglas S. Swords ◽

Ignacio Garrido-Laguna ◽

Sean J. Mulvihill ◽

Gregory J. Stoddard ◽

Matthew A. Firpo ◽

...

Keyword(s):

Overall Survival ◽

Adjuvant Chemotherapy ◽

Neoadjuvant Chemotherapy ◽

Neoadjuvant Therapy ◽

Pancreatic Adenocarcinoma ◽

Survival Benefit ◽

Cox Regression ◽

Average Treatment Effect ◽

Adjuvant Radiation ◽

Average Survival

404 Background: Guidelines for adjuvant chemotherapy in patients with resected pancreatic adenocarcinoma (PDAC) who received neoadjuvant chemotherapy are equivocal. A lymph node ratio (LNR) ≥ 0.15 may predict lack of benefit, but conflicting results are reported. Methods: The National Cancer Database was searched to identify patients who were resected after neoadjuvant chemotherapy in 2006-2013. Exclusions: metastases at surgery, 90-day postoperative mortality, adjuvant radiation, and outlier interval from diagnosis to surgery (<2.5 or >10 months). The association between adjuvant chemotherapy and overall survival (OS) from diagnosis was examined using multivariable Cox regression and inverse propensity of treatment weighted (IPTW) Cox regression. An IPTW based estimator of the average treatment effect (ATE) was used to quantify the population average survival benefit of treatment. Outcomes were examined in all patients and in those with LNR < 0.15 and ≥ 0.15. Results: 681/2488 patients (27%) received adjuvant chemotherapy. In multivariable Cox regression, adjuvant chemotherapy was associated with improved OS in the overall cohort and in patients with LNR < 0.15. A trend towards improved OS was also observed for those with LNR ≥ 0.15. After accounting for indication bias using IPTW, a significant survival benefit for was observed only for patients with LNR < 0.15. The ATE among LNR < 0.15 patients was 3.3 (95% CI 1.0, 5.7) months, indicating that the average survival of the population would be 3.3 months longer if all received treatment. Conclusions: Adjuvant chemotherapy in resected PDAC patients who received neoadjuvant therapy appears to be beneficial in patients with negative lymph nodes or minimal nodal burden. High LNR after neoadjuvant therapy may be an indicator of adverse tumor biology that is less likely to derive a therapeutic benefit. [Table: see text]

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Abstract P2-10-23: Lymphovascular Invasion (LVI) and Overall Survival in Node-negative and Node-positive Breast Cancer Patients: A Meta-analysis.

10.1158/0008-5472.sabcs12-p2-10-23 ◽

2012 ◽

Author(s):

S Sahebjam ◽

I Diaz-Padilla ◽

A Ocana ◽

B Seruga ◽

E Amir

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Cancer Patients ◽

Lymphovascular Invasion ◽

Meta Analysis ◽

Breast Cancer Patients ◽

Node Negative ◽

Node Positive ◽

Positive Breast Cancer

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Pepsinogen C is a new prognostic marker in primary breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.1995.13.1.54 ◽

1995 ◽

Vol 13 (1) ◽

pp. 54-61 ◽

Cited By ~ 33

Author(s):

F Vizoso ◽

L M Sánchez ◽

I Díez-Itza ◽

A M Merino ◽

C López-Otín

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Multivariate Analysis ◽

Prognostic Value ◽

Survival Duration ◽

Relapse Free Survival ◽

Free Survival ◽

Node Negative ◽

Pepsinogen C ◽

Node Positive

PURPOSE Here we evaluate in breast cancer patients the prognostic value of pepsinogen C, a proteolytic enzyme involved in the digestion of proteins in the stomach that is also synthesized by a significant percentage of breast carcinomas. PATIENTS AND METHODS Pepsinogen C expression was examined by immunoperoxidase staining in a series of 243 breast cancer tissue sections, and results obtained were quantified using the HSCORE system, which considers both the intensity and the percentage of cells staining at each intensity. Evaluation of the prognostic value of pepsinogen C was performed retrospectively in corresponding patients by multivariate analysis that took into account conventional prognostic factors. The mean follow-up period was 48.5 months. RESULTS A total of 113 carcinomas (46.5%) stained positively for this proteinase, but there were clear differences among them with regard to the intensity and percentage of stained cells. Pepsinogen C values were significantly higher in well differentiated (grade I, 89.1) and moderately differentiated (grade II, 88.5) tumors than in poorly differentiated (grade III, 27.7) tumors (P < .001). Similarly, significant differences in pepsinogen C content were found between estrogen receptor (ER)-positive tumors and ER-negative tumors (85.9 v 41.2, respectively; P < .05). Moreover, results indicated that low pepsinogen C content predicted shorter relapse-free survival duration and overall survival duration (P < .0001). Separate Cox multivariate analysis for relapse-free survival and overall survival in subgroups of patients as defined by node status showed that pepsinogen C expression was the strongest factor to predict both relapse-free survival and overall survival in node-positive patients (P < .0001 for both) and node-negative patients (P < .005 and P < .01, respectively). CONCLUSION Pepsinogen C is a new prognostic factor for early recurrence and death in both node-positive and node-negative breast cancer. In addition, and in contrast to most studies that concern the prognostic significance of proteolytic enzymes in cancer, pepsinogen C production by breast cancer cells is associated with lesions of favorable evolution.

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NSABP B-47: A randomized phase III trial of adjuvant therapy comparing chemotherapy alone to chemotherapy plus trastuzumab in women with node-positive or high-risk node-negative HER2-low invasive breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.tps1139 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. TPS1139-TPS1139 ◽

Cited By ~ 2

Author(s):

Louis Fehrenbacher ◽

Jong-Hyeon Jeong ◽

Priya Rastogi ◽

Charles E. Geyer ◽

Soonmyung Paik ◽

...

Keyword(s):

Breast Cancer ◽

High Risk ◽

Statistical Power ◽

Disease Free Survival ◽

Phase Iii ◽

Adjuvant Radiation ◽

Weight Changes ◽

Node Negative ◽

Node Positive ◽

Her2 Breast Cancer

TPS1139 Background: Adjuvant trastuzumab trials in HER2+ breast cancer (BC) demonstrated a large reduction in recurrence and death. Central testing showed HER2 non-amplified participants derived similar benefit. Among HER2-amplified patients (pts), multiple studies showed no effect on benefit by degree of amplification. Blinded internal and external review confirmed the non-amplified nature of the HER2 normal group. Based on these findings, NSABP B-47, sponsored by the NCI, was activated January 2011 and is actively accruing. The study is NCI central IRB approved, open via the CTSU, and endorsed by SWOG, ECOG, and RTOG. Methods: Study: Chemotherapy treatment is by physician choice: The non-anthracycline regimen is TC (docetaxel 75 mg/m2, cyclophosphamide (C) 600 mg/m2) IV q 3 wks for 6 cycles; the anthracycline regimen is AC → WP (doxorubicin 60 mg/m2 and C 600 mg/m2 IV either q 3 wks or q 2 wks [investigator discretion] for 4 cycles → paclitaxel 80 mg/m2 IV wkly for 12 doses). Pts are randomly assigned to chemotherapy with or without trastuzumab for 1 year. Pts receive adjuvant radiation therapy and endocrine therapy, as clinically indicated. Detailed menstrual history, concurrent medications, weight changes, and biomarkers (estrogen, stress, inflammation), are being collected. Eligibility: Eligibility includes: node positive or high risk node negative BC pts; HER2 IHC 1+ or 2+ scores, but non amplified by FISH; normal cardiac, renal, and liver function. Detailed eligibility will be provided. Statistical Design: The primary aim is to determine whether the addition of trastuzumab to chemotherapy improves invasive disease-free survival (IDFS). 3,260 pts will be enrolled to provide statistical power of 0.9 to detect a 33% reduction in the hazard rate of IDFS using a one-sided alpha level of 0.025. Progress: Protocol was activated in January 2011. First pt was entered in February 2011. As of January 23, 2013, 1,416 of 3,260 (43.4 %) pts have been enrolled. Updated information on enrollment and study background will be provided. Support: NCI U10-12027, -37377, 69651, 69974, and Genentech, Inc. Clinical trial information: NCT01275677.

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The role for adjuvant radiotherapy in the treatment of hemangiopericytoma: a Surveillance, Epidemiology, and End Results analysis

Journal of Neurosurgery ◽

10.3171/2013.10.jns13113 ◽

2014 ◽

Vol 120 (2) ◽

pp. 300-308 ◽

Cited By ~ 33

Author(s):

Adam M. Sonabend ◽

Brad E. Zacharia ◽

Hannah Goldstein ◽

Samuel S. Bruce ◽

Dawn Hershman ◽

...

Keyword(s):

Overall Survival ◽

Multivariate Analysis ◽

Radiation Therapy ◽

Survival Data ◽

Survival Benefit ◽

Radiation Treatment ◽

Univariate Analysis ◽

Adjuvant Radiation ◽

Significant Difference ◽

End Results

Object Central nervous system (CNS) hemangiopericytomas are relatively uncommon and unique among CNS tumors as they can originate from or develop metastases outside of the CNS. Significant difference of opinion exists in the management of these lesions, as current treatment paradigms are based on limited clinical experience and single-institution series. Given these limitations and the absence of prospective clinical trials within the literature, nationwide registries have the potential to provide unique insight into the efficacy of various therapies. Methods The authors queried the Surveillance Epidemiology and End Results (SEER) database to investigate the clinical behavior and prognostic factors for hemangiopericytomas originating within the CNS during the years 2000–2009. The SEER survival data were adjusted for demographic factors including age, sex, and race. Univariate and multivariate analyses were performed to identify characteristics associated with overall survival. Results The authors identified 227 patients with a diagnosis of CNS hemangiopericytoma. The median length of follow-up was 34 months (interquartile range 11–63 months). Median survival was not reached, but the 5-year survival rate was 83%. Univariate analysis showed that age and radiation therapy were significantly associated with survival. Moreover, young age and supratentorial location were significantly associated with survival on multivariate analysis. Most importantly, multivariate analysis using the Cox proportional hazards model showed a statistically significant survival benefit for patients treated with gross-total resection (GTR) in combination with adjuvant radiation treatment (HR 0.31 [95% CI 0.01–0.95], p = 0.04), an effect not appreciated with GTR alone. Conclusions The authors describe the epidemiology of CNS hemangiopericytomas in a large, national cancer database, evaluating the effectiveness of various treatment paradigms used in clinical practice. In this study, an overall survival benefit was found when GTR was accomplished and combined with radiation therapy. This finding has not been appreciated in previous series of patients with CNS hemangiopericytoma and warrants future investigations into the role of upfront adjuvant radiation therapy.

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Stage I-II endometrial adenocarcinoma evolution of therapeutic paradigms: the role of surgery and adjuvant radiation

International Journal of Gynecological Cancer ◽

10.1136/ijgc-00009577-200205000-00002 ◽

2002 ◽

Vol 12 (3) ◽

pp. 237-249 ◽

Cited By ~ 1

Author(s):

K Look

Keyword(s):

Overall Survival ◽

Radiation Therapy ◽

Adjuvant Radiotherapy ◽

Survival Benefit ◽

Older Patients ◽

Endometrial Adenocarcinoma ◽

Stage I ◽

Surgical Staging ◽

Adjuvant Radiation

Abstract.Look K. Stage I-II endometrial adenocarcinoma evolution of therapeutic paradigms: the role of surgery and adjuvant radiation.The objective was to review the English-language literature regarding the utility of adjuvant radiation therapy following surgery for endometrial adenocarcinoma. An OVID software (Ovid Technologies, Inc., New York, NY) search of Medline articles from 1975 to 2001 was conducted using the keywords “endometrial neoplasm,”“surgery,” and “radiation therapy.” The papers were assessed with regard to (a) extent of surgical staging (b) type of adjuvant radiotherapy utilized: external vs. brachytherapy vs. combination therapy; and (c) whether the patients were treated as part of prospective trial or reported as a descriptive series reflecting an institution's practice pattern. Survival rates are excellent for patients with early stage disease treated in either paradigm of extended-surgical staging with more restricted use of the adjuvant therapy or simple hysterectomy bilateral salpingoophorectomy with more frequent use of adjvuant radiotherapy. All three prospecctive-randomized trials (PRCT) have shown an improvement in local control but no overall survival benefit for the entire accrued group. All three PRCTs have shown a higher risk of disease recurrence in older patients or those with grade 3 histology or deep invasion. Each suggests there may be a survival benefit for the subset of patients with such high-risk features, but at present there is no prospective data that demonstrates adjuvant radiotherapy will improve the overall survival for the highest-risk subset of older patients with high-grade deeply invasive disease.

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Patterns of Care and Outcomes of Adjuvant Chemoradiation for Node-Positive Pancreatic Adenocarcinoma

Journal of Gastrointestinal Cancer ◽

10.1007/s12029-019-00265-2 ◽

2019 ◽

Vol 51 (2) ◽

pp. 506-514

Author(s):

Nikita Malakhov ◽

Anna Lee ◽

Ashley Albert ◽

Ariel Lederman ◽

John Byun ◽

...

Keyword(s):

Pancreatic Adenocarcinoma ◽

Patterns Of Care ◽

Adjuvant Chemoradiation ◽

Node Positive

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HER-2/neu oncogene protein and prognosis in breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.1989.7.8.1120 ◽

1989 ◽

Vol 7 (8) ◽

pp. 1120-1128 ◽

Cited By ~ 385

Author(s):

A K Tandon ◽

G M Clark ◽

G C Chamness ◽

A Ullrich ◽

W L McGuire

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Clinical Outcome ◽

Node Negative ◽

Node Positive ◽

Her 2 ◽

Neu Oncogene ◽

Disease Free ◽

Oncogene Protein ◽

Positive Breast Cancer

Amplification of the HER-2/neu oncogene was recently reported to predict poor clinical outcome in node-positive breast cancer patients. Since expression of the oncogene as its protein product might be even more closely related than gene amplification to disease progression, we have now examined levels of the HER-2/neu oncogene protein for its prognostic potential in both node-positive and node-negative breast cancer. Using Western blot analysis, levels of this protein were determined in 728 primary human breast tumor specimens. We examined relationships between this protein and other established markers of prognosis, as well as clinical outcome. In node-negative patients (n = 378), the HER-2/neu protein failed to predict disease outcome. However, in node-positive patients (n = 350), those patients with higher HER-2/neu protein had statistically shorter disease-free (P = .0014) and overall survival (P less than .0001) than patients with lower levels of the protein. Higher HER-2/neu protein was found in tumors without estrogen receptor (ER) (P = .02) or progesterone receptor (PgR) (P = .0003), and in patients with more than three positive lymph nodes (P = .04). A significant correlation between levels of the HER-2/neu gene protein and amplification of the gene itself was also found (n = 48, P less than .001). Multivariate analyses in these patients showed that the HER-2/neu protein is a significant independent predictor of both the disease-free and the overall survival in node-positive breast cancer, even when other prognostic factors are considered.

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