Early initiation of adjuvant chemotherapy improves survival of patients with pancreatic carcinoma after surgical resection

Murakami, Yoshiaki; Uemura, Kenichiro; Sudo, Takeshi; Hashimoto, Yasushi; Kondo, Naru; Nakagawa, Noritoshi; Sasaki, Hayato; Sueda, Taijiro

doi:10.1007/s00280-012-2029-1

Cited by 54 publications

(60 citation statements)

References 35 publications

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“…13–20 including PC. 3 Postoperative complications have been associated with worse long-term outcomes in esophageal cancer, 24,25 colorectal cancer, 26–28 and PC. 4,22,29 However, the relationship between postoperative complications following PD for PC and receipt of adjuvant therapy is unclear.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have investigated the impact of postoperative complications on long-term survival in PC, 3,4,22,29 but only two have focused on TTA. 3,29 Murakami et al 3 reported median TTA for 104 patients was only 20 days and only postoperative complications related to longer TTA.…”

Section: Discussionmentioning

confidence: 99%

“…2–7 Several studies have demonstrated early initiation of adjuvant CT is associated with improved survival for colorectal 13–17 and breast cancers. 18–20 Murakami et al 3 reported starting adjuvant CT within 20 days of pancreatic resection improves 5-year OS (52 vs. 26 %; p = 0.013) and 5-year disease-free survival (53 vs. 22 %; p = 0.007).…”

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confidence: 99%

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The Impact of Postoperative Complications on the Administration of Adjuvant Therapy Following Pancreaticoduodenectomy for Adenocarcinoma

et al. 2014

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Background The impact of postoperative complications on the administration of adjuvant therapy following pancreaticoduodenectomy (PD) for adenocarcinoma is still unclear. Methods A retrospective review of all patients undergoing PD at our institution between 1995 and 2011 was performed. Clinicopathological data, including Clavien–Dindo complication grade, time to adjuvant therapy (TTA), and survival, were analyzed. Results A total of 1,144 patients underwent PD for adenocarcinoma between 1995 and 2011. The overall complication rate was 49.1 % and clinically severe complications (≥IIIb) occurred in 4.2 %. Overall, 621 patients (54.3 %) were known to have received adjuvant therapy. The median TTA was 60 days. Although the presence of a complication was associated with a delay in TTA (p = 0.002), the grade of complication was not (p = 0.112). On multivariate analysis, only age > 68 years (p < 0.001) and length of stay >9 days (p = 0.002) correlated with no adjuvant therapy. Patients with postoperative complications were more likely to receive single adjuvant chemotherapy or radiation therapy (31.4 %) than were patients without complications (17.1 %; p < 0.001). Patients without a complication had a longer median survival compared with patients who experienced complications (19.5 vs. 16.1 months; p = 0.001). Patients without complications who received adjuvant therapy had longer median survival than patients with complications who received no adjuvant therapy (22.5 vs. 10.7 months; p < 0.001). Multivariate analysis demonstrated that complications [hazard ratio (HR) 1.16; p = 0.023] and adjuvant therapy (HR 0.67; p <0.001) were related to survival. Conclusion Complications and no adjuvant therapy are common following PD for adenocarcinoma. Postoperative complications delay TTA and reduce the likelihood of multimodality adjuvant therapy. Identifying patients at increased risk for complications and those unlikely to receive adjuvant therapy warrants further investigation as they may benefit from a neoadjuvant approach.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The Impact of Postoperative Complications on the Administration of Adjuvant Therapy Following Pancreaticoduodenectomy for Adenocarcinoma

et al. 2014

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“…Recently, the ESPAC-4 trial reported 5-year survival rates of 15% to 30% in patients with margin negative resection (R0) and adjuvant chemotherapy with either gemcitabine alone or gemcitabine in combination with capecitabine [4]. Local recurrence of the tumor occurs in up to 86% of surgical cases despite adjuvant chemotherapy [3], [4], [5], [7], [8], [9], [10]. More efficient adjuvant therapy regimens are being actively sought.…”

Section: Introductionmentioning

confidence: 99%

Proteome Profiling of Primary Pancreatic Ductal Adenocarcinomas Undergoing Additive Chemoradiation Link ALDH1A1 to Early Local Recurrence and Chemoradiation Resistance

Oria

Bronsert

Thomsen

et al. 2018

Translational Oncology

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Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis with frequent post-surgical local recurrence. The combination of adjuvant chemotherapy with radiotherapy is under consideration to achieve a prolonged progression-free survival (PFS). To date, few studies have determined the proteome profiles associated with response to adjuvant chemoradiation. We herein analyzed the proteomes of primary PDAC tumors subjected to additive chemoradiation after surgical resection and achieving short PFS (median 6 months) versus prolonged PFS (median 28 months). Proteomic analysis revealed the overexpression of Aldehyde Dehydrogenase 1 Family Member A1 (ALDH1A1) and Monoamine Oxidase A (MAOA) in the short PFS cohort, which were corroborated by immunohistochemistry. In vitro, specific inhibition of ALDH1A1 by A37 in combination with gemcitabine, radiation, and chemoradiation lowered cell viability and augmented cell death in MiaPaCa-2 and Panc 05.04 cells. ALDH1A1 silencing in both cell lines dampened cell proliferation, cell metabolism, and colony formation. In MiaPaCa-2 cells, ALDH1A1 silencing sensitized cells towards treatment with gemcitabine, radiation or chemoradiation. In Panc 05.04, increased cell death was observed upon gemcitabine treatment only. These findings are in line with previous studies that have suggested a role of ALDH1A1 chemoradiation resistance, e.g., in esophageal cancer. In summary, we present one of the first proteome studies to investigate the responsiveness of PDAC to chemoradiation and provide further evidence for a role of ALDH1A1 in therapy resistance.

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“…Ретроспективно проанализированная база данных SEER показала, что эф-фективность химиотерапии при III стадии рака поджелу-дочной железы в случае ее начала в сроки, превышающие 12 недель после операции, имеет тенденцию к снижению [12]. Нецелесообразность длительной отсрочки начала адъювантной химиотерапии подчеркивается и результа-тами других анализов [13,14].…”

unclassified

Место Адъювантной Лучевой Терапии При Раке Поджелудочной Железы – В Клинических Исследованиях

Pokataev¹

2017

Zlokač. opuholi

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Early initiation of adjuvant chemotherapy improves survival of patients with pancreatic carcinoma after surgical resection

Abstract: Adjuvant chemotherapy for patients with resected pancreatic carcinoma should be initiated as soon as possible after surgical resection. Prevention of postoperative complication is needed to enable early initiation.

Cited by 54 publications

References 35 publications

The Impact of Postoperative Complications on the Administration of Adjuvant Therapy Following Pancreaticoduodenectomy for Adenocarcinoma

The Impact of Postoperative Complications on the Administration of Adjuvant Therapy Following Pancreaticoduodenectomy for Adenocarcinoma

Proteome Profiling of Primary Pancreatic Ductal Adenocarcinomas Undergoing Additive Chemoradiation Link ALDH1A1 to Early Local Recurrence and Chemoradiation Resistance

Место Адъювантной Лучевой Терапии При Раке Поджелудочной Железы – В Клинических Исследованиях

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