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Reduced and Normalized Carbohydrate Antigen 19-9 Concentrations after Neoadjuvant Chemotherapy Have Comparable Prognostic Performance in Patients with Borderline Resectable and Locally Advanced Pancreatic Cancer.

ABSTRACT: BACKGROUND:The association between optimal carbohydrate antigen (CA) 19-9 concentration after neoadjuvant chemotherapy (NACT) and prognosis has not been confirmed in patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC). METHODS:This retrospective study included 122 patients with BRPC and 103 with LAPC who underwent surgery after NACT between 2012 and 2019 in a tertiary referral center. Prognostic models were established based on relative difference of the CA 19-9 (RDC), with their prognostic performance compared using C-index and Akaike information criterion (AIC). RESULTS:CA 19-9 concentrations of 37-1000 U/mL before NACT showed prognostic significance in patients with BRPC and LAPC (hazard ratio [HR]: 0.262; 95% confidence interval [CI]: 0.092-0.748; p = 0.012). Prognostic models in this subgroup showed that RDC was independently prognostic of better overall survival (HR: 0.262; 95% CI: 0.093-0.739; p = 0.011) and recurrence free survival (HR: 0.299; 95% CI: 0.140-0.642; p = 0.002). The prognostic performances of RDC (C-index: 0.653; AIC: 227.243), normalization of CA 19-9 after NACT (C-index: 0.625; AIC: 230.897) and surgery (C-index: 0.613; AIC: 233.114) showed no significant differences. CONCLUSION:RDC was independently associated with better prognosis after NACT in patients with BRPC or LAPC. Decreased CA19-9 after NACT was a prognostic indicator of better survival and recurrence, as was normalization of CA 19-9 after both NACT and surgery.

SUBMITTER: Lee W

PROVIDER: S-EPMC7291310 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Reduced and Normalized Carbohydrate Antigen 19-9 Concentrations after Neoadjuvant Chemotherapy Have Comparable Prognostic Performance in Patients with Borderline Resectable and Locally Advanced Pancreatic Cancer.

Lee Woohyung W Park Yejong Y Kwon Jae Woo JW Jun Eunsung E Song Ki Byung KB Lee Jae Hoon JH Hwang Dae Wook DW Yoo Changhoon C Kim Kyu-Pyo KP Jeong Jae Ho JH Chang Heung-Moon HM Ryoo Baek-Yeol BY Park Seo Young SY Kim Song Cheol SC

Journal of clinical medicine 20200514 5

<h4>Background</h4>The association between optimal carbohydrate antigen (CA) 19-9 concentration after neoadjuvant chemotherapy (NACT) and prognosis has not been confirmed in patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC).<h4>Methods</h4>This retrospective study included 122 patients with BRPC and 103 with LAPC who underwent surgery after NACT between 2012 and 2019 in a tertiary referral center. Prognostic models were established based on relative differe ...[more]

PMID: 32423123

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Project description:BackgroundThere is no agreed upon standard of care for borderline-resectable pancreatic cancer (BRPC) or locally-advanced pancreatic cancer (LAPC) patients regarding the benefit of chemotherapy or radiation alone or in combination.Patients and methodsWe completed a retrospective cohort analysis of BRPC and LAPC patients at a cancer center with expertise in multi-disciplinary pancreatic ductal adenocarcinoma (PDAC) treatment over a 5-year period from 03/01/2014 to 03/01/2019 (cut-off date). The total evaluable newly diagnosed, treatment naïve, BRPC, and LAPC patients with adequate organ function and ability to obtain treatment after multidisciplinary review was 52 patients. After analysis, patients were evaluated for rates of resection, extent of resection (R0 or R1), median progression-free survival (mPFS), and median overall survival (mOS).ResultsPatients were treated with chemotherapy alone (gemcitabine and nab-paclitaxel = 77% (20/26); FOLFIRINOX = 19% (5/26); single agent gemcitabine 3.8% (1/26)), or chemotherapy followed by chemoradiation (gemcitabine +5 Gy × 5 weeks), or chemoradiation alone prior to re-staging and potential resection. Of the 29% (15/52) of patients who went on to surgical resection, 73% (11/15) achieved R0 resection. An R0 resection was achieved in 35% (9/26) of patients treated with chemotherapy alone, 7.6% (1/13) in a patient treated with chemotherapy followed by radiation, and 7.6% (1/13) with concurrent chemoradiotherapy alone. Chemotherapy alone achieved a mPFS of 16.4 months (p < 0.0025) and mOS of 26.2 months (p < 0.0001), chemotherapy followed by chemoradiation was 13.0 months and 14.9 months respectively, while concurrent chemoradiotherapy was 6.9 months and 7.3 months.Conclusions and relevanceBRPC and LAPC patients capable of surgery after only receiving neoadjuvant treatment with chemotherapy had higher rates of R0 resection with prolonged median PFS and OS compared with any patient needing combination chemotherapy with radiotherapy.

Project description:BackgroundAs neoadjuvant therapy of borderline resectable pancreatic cancer (BRPC) is becoming more widely used, better indicators of progression are needed to help guide therapeutic decisions.Materials and methodsA retrospective review was performed on all patients with BRPC who received 24 weeks of neoadjuvant chemotherapy. Patients with chemotoxicity or medical comorbidities limiting treatment completion and nonexpressors of carbohydrate antigen 19-9 (CA19-9) were excluded. Serum CA19-9 response was analyzed as a predictor of disease progression, recurrence, and survival.ResultsOne hundred four patients were included; 39 (37%) progressed on treatment (18 local and 21 distant) and 65 (63%) were resected (68% R0). Multivariate logistic regression analysis determined that the percent decrease in CA19-9 from baseline to minimum value (odds ratio [OR] 0.947, p ≤ .0001) and the percent increase from minimum value to final restaging CA19-9 (OR 1.030, p ≤ .0001) were predictive of progression. A receiver operating characteristics curve analysis determined cutoff values predictive of progression, which were used to create four prognostic groups. CA19-9 responses were categorized as follows: (1) always normal (n = 6); (2) poor response (n = 31); (3) unsustained response (n = 19); and (4) sustained response (n = 48). Median overall survival for Groups 1-4 was 58, 16, 20, and 38 months, respectively (p ≤ .0001).ConclusionPatients with initially elevated CA19-9 levels who do not have a decline to a sustained low level are at risk for progression, recurrence, and poor survival. Alternative treatment strategies prior to an attempt at curative resection should be considered in this cohort.Implications for practiceThis study identified percent changes in carbohydrate antigen 19-9 blood levels while on chemotherapy that predict tumor growth in patients with advanced pancreas cancer. These changes could be used to better select patients who would benefit from surgical removal of their tumors and improve survival.

Project description:Pancreatic ductal adenocarcinoma (PDAC) is currently ranked fourth place of cancer related mortality. Only a minority of 10-20% of patients with PDAC have a primarily resectable disease, while 50-60% of the patients are diagnosed with irresectable disease. A certain group of patients is defined as "borderline resectable", which is mainly relied to contact of the tumor to major abdominal vessels. For preoperative evaluation of resectability CT and MRI is commonly used. Although CT-scanning, which is the standard preoperative imaging modality, has striking limitations concerning evaluation of lymph node status as well as vessel involvement and approximately 20% of the patients are staged incorrectly. A central part of modern therapy of locally advanced or not primarily resectable PDAC is neoadjuvant therapy. Especially neoadjuvant chemotherapy according to the FOLFIRINOX protocol resulted in high resection rates of initially not resectable patients. Furthermore, treatment with FOLFIRINOX was shown to be an independent predictor of improved prognosis and resection after neoadjuvant treatment with FOLFIRINOX was associated with improved survival. Neoadjuvant treatment was able to increases the rates of R0 resection, which depicts an independent prognostic factor and FOLFIRINOX outmatched other treatment regimes (e.g., gemcitabine-based radio-chemotherapy) concerning achievement of a R0 resection. While most evidence of neoadjuvant treatment of PDAC is conferred by retrospective analysis, there is growing data from randomized controlled trials, confirming the beneficial effects of neoadjuvant therapy on the prognosis of PDAC. Thus, patients with borderline resectable and locally advanced PDAC should be evaluated for neoadjuvant treatment. If there is no progression of the disease during neoadjuvant treatment exploration with the goal of R0 resection should be performed. If possible, patients should be included in well-designed randomized controlled trials at specialized pancreatic centers.

Project description:ImportanceChemotherapy is the recommended induction strategy in borderline resectable and locally advanced pancreatic ductal adenocarcinoma. However, the associated results on an intention-to-treat basis are poorly understood.ObjectiveTo investigate pragmatically the treatment compliance, conversion to surgery, and survival outcomes of patients with borderline resectable and locally advanced pancreatic ductal adenocarcinoma undergoing primary chemotherapy.Design, setting, and participantsThis prospective study took place in a national referral center for pancreatic diseases in Italy. Consecutive patients with borderline resectable and locally advanced pancreatic ductal adenocarcinoma were enrolled at the time of diagnosis (January 2013 through December 2015) and followed up to June 2018.ExposuresThe chemotherapy regimen, assigned based on multidisciplinary evaluation, was delivered either at a hub center or at spoke centers. By convention, primary chemotherapy was considered completed after 6 months. After restaging, surgical candidates were selected based on radiologic and biochemical response. All surgeries were carried out at the hub center.Main outcomes and measuresRates of receipt and completion of chemotherapy, rates of conversion to surgery, and disease-specific survival.ResultsOf 680 patients, 267 (39.3%) had borderline resectable and 413 (60.7%) had locally advanced pancreatic ductal adenocarcinoma. Overall, 66 patients (9.7%) were lost to follow-up. The rate of chemotherapy receipt was 92.9% (n = 570). The chemotherapeutic regimens most commonly used included FOLFIRINOX (fluorouracil, leucovorin, oxaliplatin, and irinotecan) (260 [45.6%]) and gemcitabine plus nanoparticle albumin-bound-paclitaxel (123 [21.6%]). Nineteen patients (3.3%) receiving chemotherapy died within 6 months, mainly for disease progression. The treatment completion rate was 71.6% (408 of 570). The overall rate of resection was 15.1% (93 of 614) (borderline resectable, 60 of 249 [24.1%]; locally advanced, 33 of 365 [9%]; resection:exploration ratio, 63.3%). Independent predictors of resection were age, borderline resectable disease, chemotherapy completion, radiologic response, and biochemical response. The median survival for the whole cohort was 12.8 (95% CI, 11.7-13.9) months. Factors independently associated with survival were completion of chemotherapy, receipt of complementary radiation therapy, and resection. In patients who underwent resection, the median survival was 35.4 (95% CI, 27.0-43.7) months for initially borderline resectable and 41.8 (95% CI, 27.5-56.1) months for initially locally advanced disease. No pretreatment and posttreatment factors were associated with survival after pancreatectomy.Conclusions and relevanceThis pragmatic observational cohort study with an intention-to-treat design provides real-world evidence of outcomes associated with the most current primary chemotherapy regimens used for borderline resectable and locally advanced pancreatic ductal adenocarcinoma.

Project description:Approximately 20% of pancreatic ductal adenocarcinoma (PDAC) patients have (borderline) resectable pancreatic cancer [(B)RPC] at diagnosis. Upfront resection with adjuvant chemotherapy has long been the standard of care for these patients. However, although surgical quality has improved, still about 50% of patients never receive adjuvant treatment. Therefore, recent developments have focused on a neoadjuvant approach. Directly comparing results from neoadjuvant and adjuvant regimens is challenging due to differences in patient populations that influence outcomes. Neoadjuvant trials include all patients who have (B)RPC on imaging, while adjuvant-only trials include patients who underwent a complete resection and recovered to a good performance status without any evidence of residual disease. Guidelines recommend neoadjuvant treatment for BRPC patients mainly to improve negative resection margin (R0) rates. For resectable PDAC, upfront resection is still considered the standard of care. However, theoretical advantages of neoadjuvant treatment, including the increased R0 resection rate, early delivery of systemic therapy to all patients, directly addressing occult metastatic disease, and improved patient selection for resection, may also apply to these patients. A systematic review by intention-to-treat showed a superior median overall survival (OS) for any neoadjuvant approach (19 months) compared to upfront surgery (15 months) in (B)RPC patients. A neoadjuvant approach was recently supported by three randomized controlled trials (RCTs). For resectable PDAC, neoadjuvant treatment was superior in a Japanese RCT of neoadjuvant gemcitabine with S-1 vs. upfront surgery, with adjuvant S-1 in both arms (median OS: 37 vs. 27 months, p = 0.015). A Korean trial of neoadjuvant gemcitabine-based chemoradiotherapy vs. upfront resection in BRPC patients was terminated early due to superiority of the neoadjuvant group (median OS: 21 vs. 12 months, p = 0.028; R0 resection: 52 vs. 26%, p = 0.004). The PREOPANC-1 trial for (B)RPC patients also showed favorable outcome for neoadjuvant gemcitabine-based chemoradiotherapy vs. upfront surgery (median OS: 17 vs. 14 months, p = 0.07; R0 resection: 63 vs. 31%, p < 0.001). FOLFIRINOX is likely a better neoadjuvant regimen, because of superiority compared to gemcitabine in both the metastatic and adjuvant setting. Currently, five RCTs evaluating neoadjuvant modified or fulldose FOLFIRINOX are accruing patients.

Dataset Information

Reduced and Normalized Carbohydrate Antigen 19-9 Concentrations after Neoadjuvant Chemotherapy Have Comparable Prognostic Performance in Patients with Borderline Resectable and Locally Advanced Pancreatic Cancer.

Publications

Reduced and Normalized Carbohydrate Antigen 19-9 Concentrations after Neoadjuvant Chemotherapy Have Comparable Prognostic Performance in Patients with Borderline Resectable and Locally Advanced Pancreatic Cancer.

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