Benefits of Conversion Surgery after Multimodal Treatment for Unresectable Pancreatic Ductal Adenocarcinoma

Background: Traditionally, the treatment options for unresectable locally advanced (UR-LA) and metastatic (UR-M) pancreatic ductal adenocarcinoma (PDAC) are palliative chemotherapy or chemoradiotherapy. The benefits of surgery for such patients remains unknown. The present study investigated clinical outcomes of patients undergoing conversion surgery (CS) after chemo(radiation)therapy for initially UR-PDAC. Methods: We recruited patients with UR-PDAC who underwent chemo(radiation)therapy for initially UR-PDAC between April 2006 and September 2017. We analyzed resectability of CS, predictive parameters for overall survival, and early recurrence (within six months). Results: A total of 468 patients (108 with UR-LA and 360 with UR-M PDAC) were enrolled in this study, of whom, 17 (15.7%) with UR-LA and 15 (4.2%) with UR-M underwent CS. The median survival time (MST) and five-year survival of patients who underwent CS was 37.2 months and 34%, respectively; significantly better than non-resected patients (nine months and 1%, respectively, p < 0.0001). MST did not differ according to UR-LA or UR-M (50.5 vs. 29.0 months, respectively, p = 0.53). Early recurrence after CS occurred in eight patients (18.8%). Lymph node metastasis, positive washing cytology, large tumor size (>35 mm), and lack of postoperative adjuvant chemotherapy were statistically significant predictive factors for early recurrence. Moreover, the site of pancreatic lesion and administration of postoperative adjuvant chemotherapy were statistically significant prognostic factors for overall survival in the patients undergoing CS. Conclusion: Conversion surgery offers benefits in terms of increase survival for initially UR-PDAC for patients who responded favorably to chemo(radiation)therapy when combined with postoperative adjuvant chemotherapy.

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Clinical Benefits of Conversion Surgery for Unresectable Pancreatic Ductal Adenocarcinoma: A Single-Institution, Retrospective Analysis

Cancers ◽

10.3390/cancers13051057 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1057

Author(s):

Yuko Mataki ◽

Hiroshi Kurahara ◽

Tetsuya Idichi ◽

Kiyonori Tanoue ◽

Yuto Hozaka ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factors ◽

Pancreatic Ductal Adenocarcinoma ◽

Multidisciplinary Treatment ◽

Locally Advanced ◽

Advanced Pancreatic Cancer ◽

Ductal Adenocarcinoma ◽

Conversion Surgery ◽

Clinical Benefits ◽

Resectable Cancer

Background: Unresectable pancreatic ductal adenocarcinoma (UR-PDAC) has a poor prognosis. Conversion surgery is considered a promising strategy for improving the prognosis of UR-PDAC. This study aimed to investigate the clinical benefits of conversion surgery in patients with UR-PDAC. Methods: We retrospectively evaluated patients with PDAC who were referred to our department for possible surgical resection between January 2006 and December 2019. Conversion surgery was performed only in patients with UR-PDAC who could expect R0 resection. We analyzed the prognostic factors for overall survival among patients who underwent conversion surgery. Results: Overall, 638 patients with advanced pancreatic cancer were enrolled in this study. According to resectability, resectable cancer (R) was present in 180 patients, borderline resectable cancer (BR) was present in 60 patients, unresectable locally advanced cancer (UR-LA) was present in 252 patients, and unresectable cancer with distant metastasis (UR-M) was present in 146 patients. Conversion surgery was performed in 20 of the 398 UR cases (5.1%). The median period between the initial therapy and conversion surgery was 15.5 months. According to the Response Evaluation Criteria in Solid Tumors (RECIST) evaluation, the treatment response was CR in one patient, PR in 13, SD in five, and PD in one. Downstaging was pathologically determined in all cases. According to the Evans grading system, grade I was observed in four patients (20%), grade IIb was observed in seven (35%), III was observed in seven (35%), and IV was observed in two (10%). We compared the overall survival period from initial treatment among patients undergoing conversion surgery; the median overall survival durations in the conversion surgery, R, BR, UR-LA, and UR-M groups were 73.7, 32.7, 22.7, 15.7, and 8.8 months, respectively. Multivariate analysis revealed that the presence or absence of chemoradiotherapy (CRT) and the RECIST partial response (PR)/complete response (CR) for the main tumor were statistically significant prognostic factors for overall survival among patients undergoing conversion surgery (p = 0.004 and 0.03, respectively). Conclusion: In UR-PDAC, it is important to perform multidisciplinary treatment, including CRT with conversion surgery.

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The predictors and patterns of the early recurrence of pancreatic ductal adenocarcinoma after pancreatectomy: the influence of pre- and post- operative adjuvant therapy

BMC Surgery ◽

10.1186/s12893-019-0644-z ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

Hironobu Suto ◽

Keiichi Okano ◽

Minoru Oshima ◽

Yasuhisa Ando ◽

Shigeo Takahashi ◽

...

Keyword(s):

Adjuvant Chemotherapy ◽

Local Recurrence ◽

Adjuvant Therapy ◽

Pancreatic Ductal Adenocarcinoma ◽

Preoperative Chemoradiotherapy ◽

Distant Recurrence ◽

Early Recurrence ◽

Ductal Adenocarcinoma ◽

Postoperative Adjuvant Chemotherapy ◽

Early Local Recurrence

Abstract Background The perioperative factors predicting or influencing early pancreatic ductal adenocarcinoma recurrence are unclear. This study attempted to identify the predictive factors for early pancreatic ductal adenocarcinoma recurrence post-pancreatectomy and the influence of pre- and post- operative adjuvant therapy. Methods One hundred and fifteen patients undergoing curative resection for pancreatic ductal adenocarcinoma between 2000 and 2016 at our institution were retrospectively analyzed. Patients were divided into two groups: those who did (n = 34) and did not (n = 81) experience a recurrence within 6 months postoperatively. Results Multivariate analyses demonstrated postoperative CA19–9 de-normalization, no postoperative adjuvant chemotherapy, and serosal invasion were independent risk factors for early recurrence (P < 0.001, P = 0.001, and P = 0.010, respectively). A subgroup analysis showed patients with (n = 51) and without (n = 64) preoperative chemoradiotherapy had different predictors. Although postoperative adjuvant chemotherapy was not a significant indicator in patients with preoperative chemoradiotherapy, CA19–9 de-normalization and no postoperative adjuvant chemotherapy were significant indicators in patients without preoperative chemotherapy. Preoperative chemotherapy strongly prevented early local recurrence while postoperative adjuvant chemotherapy prevented early distant recurrence. Conclusions CA19–9 de-normalization was an important predictor of early recurrence of pancreatic ductal adenocarcinoma. Although postoperative adjuvant chemotherapy was an important preventive measure against early recurrence, particularly for distant recurrence, preoperative chemoradiotherapy could strongly prevent the early local recurrence of pancreatic ductal adenocarcinoma. These perioperative adjuvant therapies could have a complementary relationship.

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Clinical Benefits of Conversion Surgery for Unresectable Pancreatic Ductal Adenocarcinoma: A Single-Institution, Retrospective Analysis

10.20944/preprints202102.0085.v1 ◽

2021 ◽

Author(s):

Yuko Mataki ◽

Hiroshi Kurahara ◽

Tetsuya Idichi ◽

Kiyonori Tanoue ◽

Yuto Hozaka ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factors ◽

Pancreatic Ductal Adenocarcinoma ◽

Multidisciplinary Treatment ◽

Locally Advanced ◽

Advanced Pancreatic Cancer ◽

Ductal Adenocarcinoma ◽

Conversion Surgery ◽

Clinical Benefits ◽

Resectable Cancer

BackgroundUnresectable pancreatic ductal adenocarcinoma (UR-PDAC) has a poor prognosis. Conversion surgery is considered a promising strategy for improving the prognosis of UR-PDAC. This study aimed to investigate the clinical benefits of conversion surgery in patients with UR-PDAC.Methods: We retrospectively evaluated patients with PDAC who were referred to our department for possible surgical resection between January 2006 and December 2019. Conversion surgery was performed only in patients with UR-PDAC who could expect R0 resection. We analyzed the prognostic factors for overall survival among patients who underwent conversion surgery. Results: Overall, 638 patients with advanced pancreatic cancer were enrolled in this study. According to resectability, resectable cancer (R) was present in 180 patients, borderline resectable cancer (BR) in 60, unresectable locally advanced cancer (UR-LA) in 252, and unresectable cancer with distant metastasis (UR-M) in 146. Conversion surgery was performed in 20 of the 398 UR cases (5.1%). The median period between the initial therapy and conversion surgery was 15.5 months. According to the RECIST evaluation, the treatment response was CR in one patient, PR in 13, SD in five, and PD in one. Downstaging was pathologically determined in all cases. According to the Evans grading system, grade I was observed in four patients (20%), grade IIb in seven (35%), III in seven (35%), and IV in two (10%). We compared the overall survival period from initial treatment among patients undergoing conversion surgery; the median overall survival durations in the conversion surgery, R, BR, UR-LA, and UR-M groups were 73.7, 32.7, 22.7, 15.7, and 8.8 months, respectively. Multivariate analysis revealed that the presence or absence of CRT and the RECIST PR/CR for the main tumor were statistically significant prognostic factors for overall survival among patients undergoing conversion surgery (p = 0.004 and 0.03, respectively).Conclusion: In UR-PDAC, it is important to perform multidisciplinary treatment, including CRT with conversion surgery.

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Clinical Benefits of Conversion Surgery for Unresectable Pancreatic Ductal Adenocarcinoma: A Single-Institution, Retrospective Analysis

10.20944/preprints202102.0085.v2 ◽

2021 ◽

Author(s):

Yuko Mataki ◽

Hiroshi Kurahara ◽

Tetsuya Idichi ◽

Kiyonori Tanoue ◽

Yuto Hozaka ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factors ◽

Pancreatic Ductal Adenocarcinoma ◽

Multidisciplinary Treatment ◽

Locally Advanced ◽

Advanced Pancreatic Cancer ◽

Ductal Adenocarcinoma ◽

Conversion Surgery ◽

Clinical Benefits ◽

Resectable Cancer

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The predictors and patterns of the early recurrence of pancreatic ductal adenocarcinoma after pancreatectomy: the influence of pre- and post- operative adjuvant therapy

10.21203/rs.2.11858/v3 ◽

2019 ◽

Author(s):

Hironobu Suto ◽

Keiichi Okano ◽

Minoru Oshima ◽

Yasuhisa Ando ◽

Shigeo Takahashi ◽

...

Keyword(s):

Adjuvant Chemotherapy ◽

Local Recurrence ◽

Adjuvant Therapy ◽

Pancreatic Ductal Adenocarcinoma ◽

Preoperative Chemoradiotherapy ◽

Distant Recurrence ◽

Early Recurrence ◽

Ductal Adenocarcinoma ◽

Postoperative Adjuvant Chemotherapy ◽

Early Local Recurrence

Abstract Background The perioperative factors predicting or influencing early pancreatic ductal adenocarcinoma recurrence are unclear. This study attempted to identify the predictive factors for early pancreatic ductal adenocarcinoma recurrence post-pancreatectomy and the influence of pre- and post- operative adjuvant therapy. Methods One hundred and fifteen patients undergoing curative resection for pancreatic ductal adenocarcinoma between 2000 and 2016 at our institution were retrospectively analyzed. Patients were divided into two groups: those who did (n=34) and did not (n=81) experience a recurrence within 6 months postoperatively. Results Multivariate analyses demonstrated postoperative CA19-9 de-normalization, no postoperative adjuvant chemotherapy, and serosal invasion were independent risk factors for early recurrence (P<0.001, P=0.001, and P=0.010, respectively). A subgroup analysis showed patients with (n=51) and without (n=64) preoperative chemoradiotherapy had different predictors. Although postoperative adjuvant chemotherapy was not a significant indicator in patients with preoperative chemoradiotherapy, CA19-9 de-normalization and no postoperative adjuvant chemotherapy were significant indicators in patients without preoperative chemotherapy. Preoperative chemotherapy strongly prevented early local recurrence while postoperative adjuvant chemotherapy prevented early distant recurrence. Conclusions CA19-9 de-normalization was an important predictor of early recurrence of pancreatic ductal adenocarcinoma. Although postoperative adjuvant chemotherapy was an important preventive measure against early recurrence, particularly for distant recurrence, preoperative chemoradiotherapy could strongly prevent the early local recurrence of pancreatic ductal adenocarcinoma. These perioperative adjuvant therapies could have a complementary relationship.

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The predictors and patterns of the early recurrence of pancreatic ductal adenocarcinoma after pancreatectomy: the influence of pre- and post- operative adjuvant therapy

10.21203/rs.2.11858/v2 ◽

2019 ◽

Author(s):

Hironobu Suto ◽

Keiichi Okano ◽

Minoru Oshima ◽

Yasuhisa Ando ◽

Shigeo Takahashi ◽

...

Keyword(s):

Adjuvant Chemotherapy ◽

Local Recurrence ◽

Adjuvant Therapy ◽

Pancreatic Ductal Adenocarcinoma ◽

Preoperative Chemoradiotherapy ◽

Distant Recurrence ◽

Early Recurrence ◽

Ductal Adenocarcinoma ◽

Postoperative Adjuvant Chemotherapy ◽

Early Local Recurrence

Abstract Background The perioperative factors predicting or influencing early pancreatic ductal adenocarcinoma recurrence are unclear. This study attempted to identify the predictive factors for early pancreatic ductal adenocarcinoma recurrence post-pancreatectomy and the influence of pre- and post- operative adjuvant therapy. Methods One hundred and fifteen patients undergoing curative resection for pancreatic ductal adenocarcinoma between 2000 and 2016 at our institution were retrospectively analyzed. Patients were divided into two groups: those who did (n=34) and did not (n=81) experience a recurrence within 6 months postoperatively. Results Multivariate analyses demonstrated postoperative CA19-9 de-normalization, no postoperative adjuvant chemotherapy, and serosal invasion were independent risk factors for early recurrence (P<0.001, P=0.001, and P=0.010, respectively). A subgroup analysis showed patients with (n=51) and without (n=64) preoperative chemoradiotherapy had different predictors. Although postoperative adjuvant chemotherapy was not a significant indicator in patients with preoperative chemoradiotherapy, CA19-9 de-normalization and no postoperative adjuvant chemotherapy were significant indicators in patients without preoperative chemotherapy. Preoperative chemotherapy strongly prevented early local recurrence while postoperative adjuvant chemotherapy prevented early distant recurrence. Conclusions CA19-9 de-normalization was an important predictor of early recurrence of pancreatic ductal adenocarcinoma. Although postoperative adjuvant chemotherapy was an important preventive measure against early recurrence, particularly for distant recurrence, preoperative chemoradiotherapy could strongly prevent the early local recurrence of pancreatic ductal adenocarcinoma. These perioperative adjuvant therapies could have a complementary relationship.

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The predictors and patterns of the early recurrence of pancreatic ductal adenocarcinoma after pancreatectomy: the influence of pre- and post- operative adjuvant therapy

10.21203/rs.2.11858/v4 ◽

2019 ◽

Author(s):

Hironobu Suto ◽

Keiichi Okano ◽

Minoru Oshima ◽

Yasuhisa Ando ◽

Shigeo Takahashi ◽

...

Keyword(s):

Adjuvant Chemotherapy ◽

Local Recurrence ◽

Adjuvant Therapy ◽

Pancreatic Ductal Adenocarcinoma ◽

Preoperative Chemoradiotherapy ◽

Distant Recurrence ◽

Early Recurrence ◽

Ductal Adenocarcinoma ◽

Postoperative Adjuvant Chemotherapy ◽

Early Local Recurrence

Abstract Background The perioperative factors predicting or influencing early pancreatic ductal adenocarcinoma recurrence are unclear. This study attempted to identify the predictive factors for early pancreatic ductal adenocarcinoma recurrence post-pancreatectomy and the influence of pre- and post- operative adjuvant therapy. Methods One hundred and fifteen patients undergoing curative resection for pancreatic ductal adenocarcinoma between 2000 and 2016 at our institution were retrospectively analyzed. Patients were divided into two groups: those who did (n=34) and did not (n=81) experience a recurrence within 6 months postoperatively. Results Multivariate analyses demonstrated postoperative CA19-9 de-normalization, no postoperative adjuvant chemotherapy, and serosal invasion were independent risk factors for early recurrence (P<0.001, P=0.001, and P=0.010, respectively). A subgroup analysis showed patients with (n=51) and without (n=64) preoperative chemoradiotherapy had different predictors. Although postoperative adjuvant chemotherapy was not a significant indicator in patients with preoperative chemoradiotherapy, CA19-9 de-normalization and no postoperative adjuvant chemotherapy were significant indicators in patients without preoperative chemotherapy. Preoperative chemotherapy strongly prevented early local recurrence while postoperative adjuvant chemotherapy prevented early distant recurrence. Conclusions CA19-9 de-normalization was an important predictor of early recurrence of pancreatic ductal adenocarcinoma. Although postoperative adjuvant chemotherapy was an important preventive measure against early recurrence, particularly for distant recurrence, preoperative chemoradiotherapy could strongly prevent the early local recurrence of pancreatic ductal adenocarcinoma. These perioperative adjuvant therapies could have a complementary relationship.

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Usefulness of FDG-PET in the evaluation of tumor response to proton beam therapy for locally advanced pancreatic ductal adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.4_suppl.271 ◽

2013 ◽

Vol 31 (4_suppl) ◽

pp. 271-271

Author(s):

Sachiyo Shirakawa ◽

Ippei Matsumoto ◽

Kazuki Terashima ◽

Makoto Shinzeki ◽

Sadaki Asari ◽

...

Keyword(s):

Radiation Therapy ◽

Pancreatic Ductal Adenocarcinoma ◽

Proton Beam ◽

Fdg Pet ◽

Tumor Response ◽

Locally Advanced ◽

Proton Beam Therapy ◽

Ductal Adenocarcinoma ◽

Local Tumor ◽

Functional Changes

271 Background: Evaluation of tumor response to radiation therapy in pancreatic ductal adenocarcinoma (PDA) using conventional radiological tests is difficult due to generally small size and inflammatory or fibrotic changes of radiated tissue. Although increasing evidence has shown that 18-F-fluorodeoxyglucose-positoron emission tomography (FDG-PET) can assess functional changes in various tumors, available data in PDA with radiation therapy is scarce. In this study, we investigated the role of FDG-PET in long-term monitoring tumor response to proton beam therapy (PBT) for PDA. Methods: Thirty-four locally advanced PDA patients with pre- and post-PBT FDG-PET data were included in this study. Local tumor responses by computed tomography (CT) and FDG-PET were defined as below: response group in CT (complete response: CR, partial response: PR, stable disease: SD, progressive disease: PD) was defined according to Response Evaluation Criteria in Solid Tumors, but only evaluation of primary tumor; and in FDG-PET, CR was defined as disappearance of FDG uptake, PR as decrease, SD as unchange, and PD as increase, compared to pre-PBT data. We evaluated tumor response at three different time points: 0-3, 3-6, and 6-12 months after PBT. Also serum CA19-9 values were evaluated. Results: Radiation doses were 50.4-70.2 GyE and 28 (82%) patients received concomitant chemotherapy. During the follow-up period (median 19 months), a total of 90 FDG-PET tests were performed. At the first time point, SD was noted in 90% (9/10) of patients by CT, whereas CR or PR in all by FDG-PET. At the second point, 39% (7/18) of patients demonstrated PR by CT, whereas 91% CR or PR by FDG-PET. Two patients with PD by FDG-PET were diagnosed as SD by CT, while one patient with PD by CT was diagnosed as PR by FDG-PET. At the third point, four patients with PD by FDG-PET were diagnosed as PR or SD by CT. Serum CA19-9 values supported FDG-PET findings. In four of 14 patients with serial FDG-PET, the maximum effects were noted at the second point. Conclusions: Serial FDG-PET can detect changes in local tumor response to PBT for PDA earlier and more sensitively than CT. Of note, there is the risk for false positive in early post-PBT FDG-PET.

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