Impact of care fragmentation on the outcomes of patients receiving neoadjuvant and adjuvant therapy for pancreatic adenocarcinoma

Despite decades of advancement and research into the multimodal care of pancreatic cancer, mortality after the diagnosis of pancreatic ductal adenocarcinoma remains grim. The role of adjuvant therapy following surgical resection has been well established in the literature. However, adjuvant therapy is imperfect, and outside of a clinical trial, there are high rates of omission or delayed initiation of therapy. Neoadjuvant treatment strategies continue to be explored in the management of resectable, borderline-resectable, and locally advanced unresectable pancreatic adenocarcinoma. With improved resection rates and the possibility for tumor downstaging, neoadjuvant therapy has become standard for patients with borderline-resectable and locally advanced unresectable tumors. Additional benefits of neoadjuvant therapy in the treatment of resectable tumors include improved completion rates of systemic therapy and R0 resection rates. Future clinical trials, including the use of novel treatment agents and combination treatment strategies in both neoadjuvant and adjuvant regimens, will add value to the treatment of pancreatic adenocarcinoma. Key words: adjuvant therapy, borderline-resectable pancreatic cancer, locally advanced pancreatic cancer, neoadjuvant therapy, pancreatic adenocarcinoma, resectable disease

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Neoadjuvant Therapy Followed by Resection Versus Upfront Resection for Resectable Pancreatic Cancer: A Propensity Score Matched Analysis

Journal of Clinical Oncology ◽

10.1200/jco.2016.68.5081 ◽

2017 ◽

Vol 35 (5) ◽

pp. 515-522 ◽

Cited By ~ 154

Author(s):

Ali A. Mokdad ◽

Rebecca M. Minter ◽

Hong Zhu ◽

Mathew M. Augustine ◽

Matthew R. Porembka ◽

...

Keyword(s):

Overall Survival ◽

Propensity Score ◽

Adjuvant Therapy ◽

Neoadjuvant Therapy ◽

Pancreatic Adenocarcinoma ◽

Early Stage ◽

Clinical Stage ◽

Pancreatic Head ◽

Hazard Ratio ◽

Stage I

Purpose To compare overall survival between patients who received neoadjuvant therapy (NAT) followed by resection and those who received upfront resection (UR)—as well as a subgroup of UR patients who also received adjuvant therapy—for early-stage resectable pancreatic adenocarcinoma. Patients and Methods Adult patients with resected, clinical stage I or II adenocarcinoma of the head of the pancreas were identified in the National Cancer Database from 2006 to 2012. Patients who underwent NAT followed by curative-intent resection were matched by propensity score with patients whose tumors were resected upfront. Overall survival was compared by using a Cox proportional hazards regression model. Early postoperative and oncologic outcomes were evaluated. Results We identified 15,237 patients with clinical stage I or II resected pancreatic head adenocarcinoma. From the NAT group, 2,005 patients (95%) were matched with 6,015 patients who underwent UR. The NAT group was associated with improved survival compared with UR (median survival, 26 months v 21 months, respectively; stratified log-rank P < .01; hazard ratio, 0.72; 95% CI, 0.68 to 0.78). Patients in the UR group had higher pathologic T stage (pT3 and T4: 86% v 73%; P < .01), higher positive lymph nodes (73% v 48%; P < .01), and higher positive resection margin (24% v 17%; P < .01). Compared with a subset of UR patients who received adjuvant therapy, NAT patients had a better survival (adjusted hazard ratio, 0.83; 95% CI, 0.73 to 0.89). Conclusion NAT followed by resection has a significant survival benefit compared with UR in early-stage, resected pancreatic head adenocarcinoma. These findings support the use of NAT, particularly as a patient selection tool, in the management of resectable pancreatic adenocarcinoma.

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Factors affecting the administration of adjuvant therapy in patients with pancreatic adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e15087 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e15087-e15087

Author(s):

Pablo Emilio Serrano Aybar ◽

Peter Tae Wan Kim ◽

Kenneth Leung ◽

Sean P. Cleary ◽

Steven Gallinger ◽

...

Keyword(s):

Adjuvant Therapy ◽

Pancreatic Adenocarcinoma ◽

Multivariate Logistic Regression Analysis ◽

Major Complication ◽

High Volume ◽

Lower Probability ◽

Node Negative ◽

Factors Affecting ◽

Major Complications ◽

The Impact

e15087 Background: Adjuvant therapy for pancreatic adenocarcinoma is now considered standard of care. The proportion of patients receiving adjuvant therapy (ADT) following pancreatic resection is a good quality indicator of cancer care. The aim of this study was to evaluate factors associated with receiving ADT in patients with pancreatic cancer. Methods: Between years 2000-2010, all patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma at a single high-volume hepatotopancreatobiliary center were evaluated. The impact of demographic, peri-operative and pathological risk factors affecting the administration of ADT were analyzed using univariate and multivariate logistic regression analysis. Results: There were 258 patients identified. Median age was 65 (37-84) years, 54% were females. There was a 15% margin positivity rate, 14% pancreatic leak rate, 14.7% major complication rate, and 1.2% 90 day/in-hospital mortality rate. Overall, 160/258 (70%) of patients received adjuvant therapy. On multivariate analysis; age, presence of major complications, node-negative disease and earlier era (2000-2004) were significantly associated with a lower probability of receiving ADT. Reasons for not receiving ADT were; patient preference: 20/67 (32%), not recommended: 14/67 (23%), disease recurrence: 12/67 (9.5%) and being medically unfit for ADT: 18/67 (11.5%). None of these reasons were different between time-periods except for fewer patients being offered ADT from 2000-2005 (15.4% vs. 2.5%, p <0.001). Conclusions: Thirty percent of patients do not receive ADT following pancreatectomy. Those with advanced age; node-negative disease and those who had major complications after pancreaticoduodenectomy were less likely to receive ADT. The impact of these factors should be taken into account when considering the administration of ADT.

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Impact of timing of adjuvant chemotherapy initiation on survival in pancreatic adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.355 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 355-355 ◽

Cited By ~ 1

Author(s):

Sofia Palacio ◽

Caroline Ripat ◽

Heather Stuart ◽

Danny Yakoub ◽

Nipun B. Merchant

Keyword(s):

Adjuvant Chemotherapy ◽

Adjuvant Therapy ◽

Pancreatic Adenocarcinoma ◽

Surgical Resection ◽

Hazard Model ◽

Disease Stage ◽

Cox Proportional Hazard Model ◽

Proportional Hazard ◽

Proportional Hazard Model ◽

Cox Proportional Hazard

355 Background: Pancreatic adenocarcinoma (PDAC) is now the third leading cause of cancer death. Surgical resection followed by adjuvant chemotherapy has been the standard of care. Due to the significant risk of morbidity following pancreatic surgery, initiation of adjuvant chemotherapy is often delayed. Prior prospective adjuvant trials have suggested that adjuvant therapy can be initiated as late as 12 weeks without detriment, but data regarding the effectiveness of beginning adjuvant therapy beyond that time remains unknown. Methods: We retrospectivelyreviewed data from the National Cancer Data Base (2004-2014) and included adult patients (pts) with PDAC with pathologic stage I-IIB who underwent surgical resection with curative intent. The primary outcome was overall survival (OS) based on time to adjuvant chemotherapy post-surgery as defined by postoperative weeks. Data were analyzed using Cox proportional hazard model and Kaplan-Meier survival curves. Results: 5279 pts. had surgery alone and 4,537 pts. received adjuvant chemotherapy. The median age was 64 years. 52% were male, 88% were white, 46% were treated at comprehensive community cancer centers. The primary surgical approach was whipple procedure in 61% of pts. 63% pts. received single agent chemotherapy and the mean time from surgery to chemotherapy was 61 days. Adjuvant chemotherapy was associated with improved OS irrespective of disease stage compared to those undergoing surgery alone (median OS for surgery alone 14 months vs adjuvant chemotherapy 21 months, p < 0.001). Cox proportional hazard model controlling for stage, surgical technique, lymph node dissection and margin status revealed improved OS in pts. receiving adjuvant chemotherapy. No significant differences in OS were seen for pts. starting adjuvant chemotherapy at 3, 6, 9, 12, 16, 20 or 24 weeks after surgical resection. Conclusions: Current guidelines recommend initiation of adjuvant chemotherapy prior to 12 weeks after pancreatic resection. Initiating adjuvant chemotherapy even up to six months post-operatively improves OS compared to those undergoing surgery alone. Our data supports the use of adjuvant chemotherapy if indicated regardless of time of surgery.

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Survival outcomes of adjuvant chemotherapy combined with radiation versus chemotherapy alone following pancreatectomy for distal pancreatic adenocarcinoma: Single institution experience.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.388 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 388-388

Author(s):

Bhavina D O Batukbhai ◽

Joseph M. Herman ◽

Marianna Zahurak ◽

Daniel A. Laheru ◽

Dung T. Le ◽

...

Keyword(s):

Adjuvant Therapy ◽

Distal Pancreatectomy ◽

Pancreatic Adenocarcinoma ◽

Disease Free Survival ◽

The Body ◽

Survival Outcomes ◽

P Value ◽

Tumor Diameter ◽

Combined Modality ◽

Significant Difference

388 Background: There is limited data of survival following distal pancreatectomy and adjuvant therapy in patients with distal pancreatic adenocarcinoma. This study aimed to evaluate the survival following combined modality (chemo-radiation and chemotherapy) compared to chemotherapy alone following distal pancreatectomy (DP). Methods: Patients who underwent DP for adenocarcinoma of the body or tail of the pancreas between the years 2000 and 2015 at Johns Hopkins were included. Comparison analysis was performed between patients who received combined modality versus chemotherapy alone. Kaplan- Meier curve was used to estimate the median overall survival (OS) and the disease free survival (DFS) at 1, 3 and 5 years after pancreatectomy. Results: A total of 294 patients underwent DP at our institution. Patients were excluded if adjuvant therapy was not administered, developed metastasis prior to adjuvant therapy, had stage IV disease at the time of surgery, received neoadjuvant therapy or had inadequate follow up at our institution to assess survival outcomes. We included a total of 105 patients, of which 45 patients received chemotherapy alone and 60 patients received combined modality. The two groups were similar with respect to nodal and margin status. Patients treated with combined modality had larger > 3cm tumors (p = 0.02). Median OS with combined modality was 60.6 mo and 50.2 mo with chemotherapy only. DFS was 15.2 mo with combined modality and 17.6 mo with chemotherapy only. There was no significant difference between the groups for OS (p = 0.73) or DFS (p = 0.495). Further analysis showed a trend away from chemoradiation in the recent years. Thirty patients (29%) received multi-agent chemotherapy in the adjuvant setting. A tumor diameter > 3cm was a predictive factor for receiving chemoradiation (chi-square p value 0.02). Conclusions: There is no difference in survival with combined modality compared to chemotherapy alone as adjuvant therapy following DP. All patients in this study received adjuvant therapy. We report a higher survival than previously described which could suggest a different biology for distal tumors.

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Survival outcomes between surgery with adjuvant therapy compared to neoadjuvant therapy with surgery in stage I pancreatic adenocarcinoma: Results from a large national cancer database.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.4_suppl.335 ◽

2019 ◽

Vol 37 (4_suppl) ◽

pp. 335-335 ◽

Cited By ~ 2

Author(s):

Samit Kumar Datta ◽

Geoffrey Belini ◽

Maharaj Singh ◽

Wesley Allan Papenfuss ◽

Federico Augusto Sanchez ◽

...

Keyword(s):

Overall Survival ◽

Adjuvant Therapy ◽

Neoadjuvant Therapy ◽

Pancreatic Adenocarcinoma ◽

Reference Group ◽

Clinical Stage ◽

National Cancer Database ◽

Nccn Guidelines ◽

Significant Difference ◽

Stage 1

335 Background: There has been a paradigm shift in the treatment of stage 1 pancreatic adenocarcinoma (PAC) from surgery first followed by adjuvant therapy (AT) to Neoadjuvant therapy (NAT) first followed by surgery and this is reflected in the current NCCN guidelines as well. Data comparing these two modalities are limited. AIM: To compare long time survival between surgery vs Surgery + AT and NAT + Surgery in a large National Cancer Database. Methods: We identified patients with surgically resected AJCC clinical stage 1, 1A, and 1B PAC between 2004-2014. Patients were stratified into 3 groups to assess outcomes. Exclusion criteria: those with incomplete survival and sequence of therapy data. Hazard ratios (HR) were calculated for evaluation of survival, as well as for 30-Day and 90-Day Mortality between the 3 groups. Results were adjusted for age and Deyo-Charlson comorbidity index. Results: A total of 9684 pts with Clincal stage 1, 1A, 1B PAC between 2004-2014 were identified. Of these 2266 pts underwent surgery alone; 6222 had surgery followed by AT; and 1196 pts had neoadjuvant therapy followed by surgery. There was a HR of 0.995 (95% CI 0.935-1.058 p = 0.864) and 0.984 (95% CI 0.924-1.048, p = 0.617) for 30- and 90-Day mortality comparing upfront surgery to NAT, respectively. With AT as the reference group for survival, there was a HR of 1.362 (95% CI 1.286-1.443, p < 0.001) for surgery only and HR of 0.929 (95% CI 0.859-1.004, p = 0.064) for NAT. Conclusions: 1. Surgery alone had worse overall survival. 2. There was no significant difference in overall survival when comparing AT and NAT 3. A prospective randomized trial evaluating the differences in survival is needed.

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