Racial Disparities in the Outcomes of Patients With Stage IV Pancreatic Adenocarcinoma Are Mediated by Chemotherapy Utilization

Objectives: To evaluate the role of stereotactic body radiotherapy (SBRT) as a local ablative treatment (LAT) in oligometastatic pancreatic cancer. Methods: Patients affected by histologically confirmed stage IV pancreatic adenocarcinoma were included in this analysis. Endpoints are local control (LC), progression-free survival (PFS), and overall survival (OS). Results: From 2013 to 2017, a total of 41 patients were treated with SBRT on 64 metastases. Most common sites of disease were lung (29.3%) and liver (56.1%). LC at 1 and 2 years were 88.9% (95% CI 73.2–98.6) and 73.9% (95% CI 50–87.5), respectively. Median LC was 39.9 months (95% CI 23.3—not reached). PFS rates at 1 and 2 years were 21.9% (95% CI 10.8–35.4) and 10.9% (95% CI 3.4–23.4), respectively. Median PFS was 5.4 months (95%CI 3.1–11.3). OS rates at 1 and 2 years were 79.9% (95% CI 63.7–89.4) and 46.7% (95% CI 29.6–62.2). Median OS was 23 months (95%CI 14.1–31.8). Conclusions: Our results, although based on a retrospective analysis of a small number of patients, show that patients with oligometastatic pancreatic cancer may benefit from local treatment with SBRT. Larger studies are warranted to confirm these results. Advances in knowledge: Selected patients affected by oligometastatic pancreatic adenocarcinoma can benefit from local ablative approaches, like SBRT

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Abstract B110: Racial disparities in pancreatic adenocarcinoma survival. Do they exist for patients who already survived their first year?

10.1158/1538-7755.disp19-b110 ◽

2020 ◽

Author(s):

Anas M Saad ◽

Maha AT Elsebaie ◽

Mohamed Amgad ◽

Muneer J Al-Husseini ◽

Kyrillus S Shohdy ◽

...

Keyword(s):

Racial Disparities ◽

Pancreatic Adenocarcinoma ◽

First Year

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Influence of post-resection time to chemotherapy in pancreatic adenocarcinoma on overall survival.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e15791 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e15791-e15791

Author(s):

Stephen Abel ◽

Richard White ◽

Suzanne Schiffman ◽

Kenneth Williams ◽

Shyam Thakkar ◽

...

Keyword(s):

Overall Survival ◽

Adjuvant Chemotherapy ◽

Pancreatic Adenocarcinoma ◽

Stage Iv ◽

Past Research ◽

Multivariable Logistic Regression Analysis ◽

Before And After ◽

Receiver Operator Curve Analysis ◽

Distant Spread ◽

Stage 1

e15791 Background: Pancreatic adenocarcinoma is an aggressive malignancy with a high propensity for distant spread. To date, surgery remains the only potentially curative treatment option; which has traditionally been followed by adjuvant chemotherapy. Past research from the pancreatic literature as well as other disease sites has shown conflicting outcomes as it relates to timely delivery of adjuvant chemotherapy. We thus used the National Cancer Database (NCDB) to evaluate time to initiation of chemotherapy following pancreatic resection and if there was any correlate with outcome. Methods: We identified patients diagnosed with stage 1-3 pancreatic adenocarcinoma in the NCDB, excluding those with stage IV disease, those treated nonoperatively, with adjuvant or neoadjuvant chemotherapy or radiotherapy and those with unknown or inadequate ( < 3 months) follow-up. Receiver operator curve analysis identified an interval of 66 days as associated with outcome. Multivariable logistic regression analysis identified variables associated with increased time to chemotherapy postoperatively ( > 66 days). Propensity matching was done to account for indication bias. Overall survival (OS) was compared between both propensity-matched groups receiving earlier and postponed chemotherapy post-resection, with an additional breakdown by stage. Results: In total, 6,873 and 3,348 patients received chemotherapy before and after the 66 day cutoff, respectively. Predictors of expedited chemotherapy included lower comorbidity, treatment outside a community program in an urban location, having insurance, Caucasian race and treatment after 2009. Median overall survival was 21.8 months for all patients and of these, 6462 were stage 1. 5-year OS was 20% in patients receiving chemotherapy within 66 days and 18% in those not (p = 0.0266). In stage 1 patients, 5-year OS was 23% versus 21% (p = 0.0116) in favor of expedited chemotherapy. In stage 2 patients, 5-year OS was 16% in both arms (p = 0.7231). Higher stage and comorbidity score, treatment at a community cancer program, lower salary, increased time from surgical resection to chemotherapy, higher grade, positive margins, and more distant year of treatment were associated with worse prognosis. Conclusions: The present propensity-matched analysis showed a significant benefit to earlier delivery of chemotherapy in the adjuvant setting, with the largest benefit seen in stage 1 patients.

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Sa007 RACIAL DISPARITIES AMONG PATIENTS UNDERGOING PANCREATICODUODENECTOMY (WHIPPLE'S PROCEDURE) FOR PANCREATIC ADENOCARCINOMA OR CHOLANGIOCARCINOMA

Gastroenterology ◽

10.1016/s0016-5085(21)01638-3 ◽

2021 ◽

Vol 160 (6) ◽

pp. S-387

Author(s):

Ahmed Eltelbany ◽

Osama Hamid ◽

Abdul Mohammed ◽

George Khoudari ◽

Sushrut Trakroo ◽

...

Keyword(s):

Racial Disparities ◽

Pancreatic Adenocarcinoma ◽

Whipple’S Procedure

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Investigation of Racial Disparities in Early Supportive Medication Use and End-of-Life Care Among Medicare Beneficiaries With Stage IV Breast Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2015.64.8162 ◽

2016 ◽

Vol 34 (19) ◽

pp. 2265-2270 ◽

Cited By ~ 19

Author(s):

Devon K. Check ◽

Cleo A. Samuel ◽

Donald L. Rosenstein ◽

Stacie B. Dusetzina

Keyword(s):

Breast Cancer ◽

Racial Disparities ◽

End Of Life ◽

End Of Life Care ◽

White Women ◽

Medication Use ◽

Stage Iv ◽

Life Care ◽

Black And White ◽

Stage Iv Breast Cancer

Purpose Early supportive care may improve quality of life and end-of-life care among patients with cancer. We assessed racial disparities in early use of medications for common cancer symptoms (depression, anxiety, insomnia) and whether these potential disparities modify end-of-life care. Methods We used 2007 to 2012 SEER-Medicare data to evaluate use of supportive medications (opioid pain medications and nonopioid psychotropics, including antidepressants/anxiolytics and sleep aids) in the 90 days postdiagnosis among black and white women with stage IV breast cancer who died between 2007 and 2012. We used modified Poisson regression to assess the relationship between race and supportive treatment use and end-of-life care (hospice, intensive care unit, more than one emergency department visit or hospitalization 30 days before death, in-hospital death). Results The study included 752 white and 131 black women. We observed disparities in nonopioid psychotropic use between black and white women (adjusted risk ratio [aRR], 0.51; 95% CI, 0.35 to 0.74) but not in opioid pain medication use. There were also disparities in hospice use (aRR, 0.86; 95% CI, 0.74 to 0.99), intensive care unit admission or more than one emergency department visit or hospitalization 30 days before death (aRR, 1.28; 95% CI, 1.01 to 1.63), and risk of dying in the hospital (aRR, 1.59; 95% CI, 1.22 to 2.09). Supportive medication use did not attenuate end-of-life care disparities. Conclusion We observed racial disparities in early supportive medication use among patients with stage IV breast cancer. Although they did not clearly attenuate end-of-life care disparities, medication use disparities may be of concern if they point to disparities in adequacy of symptom management given the potential implications for quality of life.

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Validation of SFRP1 Promoter Hypermethylation in Plasma as a Prognostic Marker for Survival and Gemcitabine Effectiveness in Patients with Stage IV Pancreatic Adenocarcinoma

Cancers ◽

10.3390/cancers13225717 ◽

2021 ◽

Vol 13 (22) ◽

pp. 5717

Author(s):

Benjamin Emil Stubbe ◽

Stine Dam Henriksen ◽

Poul Henning Madsen ◽

Anders Christian Larsen ◽

Henrik Bygum Krarup ◽

...

Keyword(s):

Pancreatic Adenocarcinoma ◽

Prognostic Marker ◽

Cox Regression ◽

Stage Iv ◽

Promoter Hypermethylation ◽

Polymerase Chain Reaction Analysis ◽

Rank Test ◽

Independent Prognostic Marker ◽

Bisulfite Treatment ◽

Kaplan Meier

No reliable predictive blood-based biomarkers are available for determining survival from pancreatic adenocarcinoma (PDAC). This combined discovery and validation study examines promoter hypermethylation (ph) of secreted frizzled-related protein 1 (SFRP1) in plasma-derived cell-free DNA as an independent prognostic marker for survival and Gemcitabine effectiveness in patients with stage IV PDAC. We conducted methylation-specific polymerase chain reaction analysis of the promoter region of the SFRP1 gene, based on bisulfite treatment. Survival was analyzed with Kaplan–Meier curves, log-rank test, and Cox regression. The discovery cohort included 40 patients, 25 receiving Gem. Gem-treated patients with phSFRP1 had a shorter median overall survival (mOS) (4.4 months) than unmethylated patients (11.6 months). Adjusted Cox-regression yielded a hazard rate (HR) of 3.48 (1.39–8.70). The validation cohort included 58 Gem-treated patients. Patients with phSFRP1 had a shorter mOS (3.2 months) than unmethylated patients (6.3 months). Adjusted Cox regression yielded an HR of 3.53 (1.85–6.74). In both cohorts, phSFRP1 was associated with poorer survival in Gem-treated patients. This may indicate that tumors with phSFRP1 are more aggressive and less sensitive to Gem treatment. This knowledge may facilitate tailored treatment of patients with stage IV PDAC. Further studies are planned to examine phSFRP1 in more intensive chemotherapy regimens.

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A case of metastatic pancreatic adenocarcinoma confounded by complementary and alternative medicine therapies

BMJ Case Reports ◽

10.1136/bcr-2019-231356 ◽

2019 ◽

Vol 12 (10) ◽

pp. e231356 ◽

Cited By ~ 1

Author(s):

Ken M Stern ◽

Bryan S Benn

Keyword(s):

Alternative Medicine ◽

Complementary And Alternative Medicine ◽

Pancreatic Adenocarcinoma ◽

Pulmonary Metastasis ◽

Alternative Therapy ◽

Stage Iv ◽

Treatment Delays ◽

Metastatic Pancreatic Adenocarcinoma ◽

History Of ◽

Complementary And Alternative

The use of complementary and alternative medicine (CAM) among cancer patients is widespread. Using these therapies may lead to treatment delays or confound the clinical picture when problems arise. Inquiry regarding CAM therapies used is an important part of a thorough history for any cancer patient. A 48-year-old man with a history of stage IV pancreatic adenocarcinoma was referred for a second opinion for a worsening dry cough in the setting of cavitary ground-glass opacities and non-cavitating nodules found on chest CT. Previous workup was non-diagnostic and his CT findings were atypical for pulmonary metastasis. Due to his extensive alternative therapy use, he was diagnosed with interstitial lung disease (ILD). Flexible bronchoscopy with transbronchial cryobiopsies revealed adenocarcinoma with intestinal/pancreatobiliary differentiation, consistent with metastatic pancreatic cancer. Adjacent alveolar parenchyma was without evidence of ILD. Atypical CT patterns of pulmonary metastasis should lead to an investigation regarding other possible causes.

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Association of SNPs in ABCC1 gene with overall survival in stage IV pancreatic adenocarcinoma patients treated with gemcitabine monotherapy

Journal of Clinical Oncology ◽

10.1200/jco.2008.26.15_suppl.14504 ◽

2008 ◽

Vol 26 (15_suppl) ◽

pp. 14504-14504

Author(s):

H. Ueno ◽

Y. Sato ◽

T. Okusaka ◽

J. Furuse ◽

H. Ishii ◽

...

Keyword(s):

Overall Survival ◽

Pancreatic Adenocarcinoma ◽

Stage Iv

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Effect of MM-141 on gemcitabine and nab-paclitaxel potentiation in preclinical models of pancreatic cancer through induction of IGF-1R and ErbB3 degradation.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.289 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 289-289 ◽

Cited By ~ 3

Author(s):

Emily Pace ◽

Sharlene Adams ◽

Adam Camblin ◽

Michael Curley ◽

Victoria Rimkunas ◽

...

Keyword(s):

Pancreatic Cancer ◽

Pancreatic Adenocarcinoma ◽

Cell Lines ◽

Stage Iv ◽

Akt Signaling ◽

Preclinical Models ◽

Patient Response ◽

Receptor Complexes

289 Background: Gemcitabine, the first-line treatment for pancreatic cancer, has been improved by addition of nab-paclitaxel. However, patient response to this regimen is limited. Oncogenic insulin-like growth factor 1 (IGF-1) and heregulin (HRG) signaling are associated with increased cancer risk and decreased response to anti-metabolites and taxanes. Therefore, we explored MM-141, a novel bispecific antibody that blocks ErbB3 and IGF-1 receptor (IGF-1R) signaling, in combination with nab-paclitaxel and gemcitabine in preclinical models of pancreatic cancer. Methods: Combinations with MM-141, gemcitabine, and nab-paclitaxel were investigated in pancreatic cancer cell lines, in vitro and in vivo. The effects of MM-141, gemcitabine, and nab-paclitaxel on tumor growth and signaling were measured by 3D spheroid growth, ELISA, Western, and mouse xenograft experiments. Results: In vitro studies show that IGF-1 and HRG are potent activators of AKT signaling, leading to increased pancreatic tumor cell proliferation and decreased sensitivity to gemcitabine and nab-paclitaxel. MM-141 inhibits ligand-induced AKT activation, induces IGF-1R and ErbB3 degradation better than a mixture of IGF-1R and ErbB3 antibodies, and sensitizes cells to gemcitabine and nab-paclitaxel, in vitro. In vivo, MM-141 combines favorably with a nab-paclitaxel/gemcitabine regimen, leading to curative outcomes in a subset of treated mice. Conclusions: ErbB3 and IGF-1R co-inhibition is required to inhibit AKT signaling in pancreatic adenocarcinoma cell lines. These receptors are associated with chemoresistance to gemcitabine and nab-paclitaxel, which is abrogated by co-administration with MM-141. MM-141-induced degradation of oncogenic receptor complexes is likely essential to reverse chemoresistance and enhance effects of the nab-paclitaxel/gemcitabine regimen. These data, taken together with wide-spread expression of IGF-1R and ErbB3 in Stage IV pancreatic adenocarcinoma tissue, support clinical exploration of a MM-141/nab-paclitaxel/gemcitabine regimen in frontline metastatic pancreatic cancer. Preparations for a randomized Phase 2 study are underway.

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