The benefit of adjuvant radiotherapy on overall survival in resected stage I to II pancreatic cancer: A propensity-adjusted analysis

Background The survival time of patients with early pancreatic cancer (PC) is still disappointing, even after surgical resection. PC has an extremely poor prognosis. Herein, we aimed to investigate the survival effect of postoperative radiotherapy (PORT) on resected stage I to II PC. Material and methods A large eligible sample of patients was identified from 2010 to 2015 from the Surveillance, Epidemiology, and End Results (SEER) registry. Survival analysis was conducted to evaluate the efficiency of PORT. Propensity score matching (PSM) analysis was used to reduce selection bias and to make the groups comparable. Results A total of 3219 patients with resected stage I to II PC was included after rigid screening. The median overall survival (OS) was 26 months with PORT (n = 1055) versus 21 months with non-PORT (n = 2164) before matching (p<0.001). By multivariable analysis, PORT remained a favorable prognostic predictor for OS. In PSM analysis, receiving PORT was associated with improved OS (median, 26 months vs. 23 months; at 2 years, 51.7% vs. 46.7%; at 5 years, 23.3% vs. 17.4% (P = 0.006). After further meticulous exploration, only the stage IIB subgroup benefited from PORT (p<0.001). This result was due to the positive lymph node state (N+), whose mortality risk was cut by 23.4% (p<0.001) by PORT. Conclusion Addition of PORT to the treatment of patients with resected stage I to II PC conveys a survival benefit, particularly among those with N-positive or stage IIB disease.

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Outcome analysis of chemotherapy duration for resected stage I-II and unresected stage III pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.4_suppl.375 ◽

2019 ◽

Vol 37 (4_suppl) ◽

pp. 375-375

Author(s):

Sung Jun Ma ◽

Austin J Iovoli ◽

Kavitha M Prezzano ◽

Gregory Hermann ◽

Lucas M Serra ◽

...

Keyword(s):

Pancreatic Cancer ◽

Propensity Score ◽

Propensity Score Matching ◽

Locally Advanced ◽

Multivariable Analysis ◽

Advanced Pancreatic Cancer ◽

Stage I ◽

Stage Iii ◽

Outcome Analysis ◽

Resected Stage

375 Background: For resected early-stage pancreatic cancer, RTOG 9704 has evaluated the outcome of 3 weeks of adjuvant chemotherapy (C) followed by chemoradiation (CRT) and post-CRT C. For locally advanced pancreatic cancer, a recent literature review showed that the typical duration for induction C is between 1 and 6 months prior to CRT. The ideal duration of C prior to CRT remains unclear. This National Cancer Database (NCDB) study was performed to identify the optimal duration of C prior to CRT in patients with pancreatic cancer. Methods: The NCDB was queried for primary stage I-II, cT1-3N0-1M0, resected and stage III, cT4N0-1M0, unresected pancreatic adenocarcinoma treated with C+CRT (2004-2015). Cohorts I-II and III included stage I-II and stage III cases, respectively. In each cohort, the patients were stratified by the short (short C) and long duration (long C) of chemotherapy based on their median durations (70 and 90 days between the onset of chemotherapy and radiation for cohorts I-II and III, respectively). Baseline patient, tumor, and treatment characteristics were examined. The primary endpoint was overall survival (OS). Kaplan-Meier analysis, multivariable Cox proportional hazards method, and propensity score matching were used. Results: Among 1,577 patients, cohort I-II had 839 patients (n = 409 with short C, n = 430 with long C) and cohort III had 738 patients (n = 360 with short C, n = 378 with long C). Median follow-up was 39.5 months and 24.3 months for cohorts I-II and III, respectively. The long C group showed improved OS in the multivariable analysis in both cohort I-II (HR 0.72, p < 0.001) and cohort III (HR 0.83, p = 0.025). Using 1:1 propensity score matching, a total of 610 patients for cohort I-II and 542 patients for cohort III were matched. After matching, long C remained statistically significant for improved OS compared with short C in both cohort I-II (median OS 26.1 vs 21.9 months, p = 0.003) and cohort III (median OS 16.7 vs 14.2 months, p = 0.021). Conclusions: Our NCDB study using propensity score matched analysis showed a survival benefit in the use of longer duration chemotherapy compared to shorter duration chemotherapy for both resected stage I-II and unresected stage III pancreatic cancer.

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Cathepsin D Expression and Gemcitabine Resistance in Pancreatic Cancer

JNCI Cancer Spectrum ◽

10.1093/jncics/pkz060 ◽

2019 ◽

Vol 4 (1) ◽

Cited By ~ 1

Author(s):

Ujjwal M Mahajan ◽

Elisabetta Goni ◽

Enno Langhoff ◽

Qi Li ◽

Eithne Costello ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Cathepsin D ◽

Median Overall Survival ◽

Validation Cohort ◽

Multivariable Analysis ◽

Predictive Marker ◽

Acid Sphingomyelinase ◽

Ductal Adenocarcinoma ◽

Gemcitabine Resistance

Abstract Background Cathepsin-D (CatD), owing to its dual role as a proteolytic enzyme and as a ligand, has been implicated in cancer progression. The role of CatD in pancreatic ductal adenocarcinoma is unknown. Methods CatD expression quantified by immunohistochemistry of tumor-tissue microarrays of 403 resected pancreatic cancer patients from the ESPAC-Tplus trial, a translational study within the ESPAC (European Study Group for Pancreatic Cancer) trials, was dichotomously distributed to low and high H scores (cut off 22.35) for survival and multivariable analysis. The validation cohort (n = 69) was recruited based on the hazard ratio of CatD from ESPAC-Tplus. 5-fluorouracil-, and gemcitabine-resistant pancreatic cancer cell lines were employed for mechanistic experiments. All statistical tests were two-sided. Results Median overall survival was 23.75 months and median overall survival for patients with high CatD expression was 21.09 (95% confidence interval [CI] = 17.31 to 24.80) months vs 27.20 (95% CI = 23.75 to 31.90) months for low CatD expression (χ2LR, 1DF = 4.00; P = .04). Multivariable analysis revealed CatD expression as a predictive marker in gemcitabine-treated (z stat = 2.33; P = .02) but not in 5-fluorouracil-treated (z stat = 0.21; P = .82) patients. An independent validation cohort confirmed CatD as a negative predictive marker for survival (χ2LR, 1DF = 6.80; P = .009) and as an independent predictive marker in gemcitabine-treated patients with a hazard ratio of 3.38 (95% CI = 1.36 to 8.38, P = .008). Overexpression of CatD was associated with a concomitant suppression of the acid sphingomyelinase, and silencing of CatD resulted in upregulation of acid sphingomyelinase with rescue of gemcitabine resistance. Conclusions Adjuvant gemcitabine is less effective in pancreatic ductal adenocarcinoma with high CatD expression, and thus CatD could serve as a marker for biomarker-driven therapy.

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Comparison of adjuvant chemotherapy, chemoradiation, and chemotherapy followed by chemoradiation for resected stage I-II pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.4_suppl.372 ◽

2019 ◽

Vol 37 (4_suppl) ◽

pp. 372-372

Author(s):

Sung Jun Ma ◽

Gregory Hermann ◽

Kavitha M Prezzano ◽

Lucas M Serra ◽

Austin J Iovoli ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Adjuvant Chemotherapy ◽

Propensity Score ◽

Propensity Score Matching ◽

Multivariable Analysis ◽

Cox Proportional Hazards ◽

Stage I ◽

Concurrent Chemoradiation ◽

Forest Plot

372 Background: Prior National Cancer Database (NCDB) studies have demonstrated an overall survival (OS) benefit for adjuvant concurrent chemoradiation (CRT) compared to chemotherapy alone. Given the more recent adoption of postoperative chemotherapy followed by concurrent chemoradiation (C+CRT), this NCDB analysis evaluates the clinical outcomes of C+CRT compared to CRT alone or adjuvant chemotherapy alone (C) for resected pancreatic cancer. Methods: The NCDB was queried for primary stage I-II, cT1-3N0-1M0, resected pancreatic adenocarcinoma treated with adjuvant C, CRT, or C+CRT (2004-2015). Patients treated with C+CRT were compared with those treated with C (cohort C) or with CRT (cohort CRT). The primary endpoint was overall survival (OS). Baseline patient, tumor, and treatment characteristics were examined. Kaplan-Meier analysis, multivariable Cox proportional hazards method, forest plot, and propensity score matching were used. Results: Among 5667 patients (n = 3031 for C, n = 1307 for CRT, n = 1329 for C+CRT), median follow-up was 34.7 months, 45.2 months, and 39.7 months for the C, CRT, and C+CRT cohorts, respectively. In the multivariable analysis for all patients, C (HR 1.31, p < 0.001) and CRT (HR 1.24, p < 0.001) were associated with worse mortality compared to C+CRT. Treatment interactions were seen among pathologically node positive disease. C+CRT was favored in 1-3 (HR 0.74, p < 0.001) and 4+ (HR 0.75, p < 0.001) positive lymph node disease when compared to C or CRT alone, but none of the treatment options were significantly favored in node negative disease (HR 0.96, p = 0.67). Using 1:1 propensity score matching, 2152 patients for cohort C and 1774 patients for cohort CRT were matched. C+CRT remained significant for improved OS for both cohort C (median OS 23.3 vs 20.0 months, p < 0.001) and cohort CRT (median OS 23.4 vs 20.8 months, p < 0.001). Conclusions: This NCDB study using propensity score matched analysis demonstrates an OS benefit for C+CRT compared to C or CRT alone following surgical resection of pancreatic cancer. Most of this benefit is in patients with positive lymph nodes.

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Analysis of radiotherapy impact on survival in resected stage I/II pancreatic cancer patients: a population-based study

BMC Cancer ◽

10.1186/s12885-021-08288-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Dong Han ◽

Fei Gao ◽

Jin Long Liu ◽

Hao Wang ◽

Qi Fu ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Survival Time ◽

Median Survival ◽

Median Survival Time ◽

Population Based ◽

Stage I ◽

Stage Ii ◽

Resected Stage ◽

Risk Of Cancer

Abstract Background The application of radiotherapy (RT) in pancreatic cancer remains controversial. Aim The aim of the study was to evaluate the efficacy of radiotherapy (neoadjuvant and adjuvant radiotherapy) for resectable I/II pancreatic cancer. Methods Fourteen thousand nine hundred seventy-seven patients with pancreatic cancer were identified from SEER database from 2004 to 2015. Multivariate analyses were performed to determine factors including RT on overall survival. Overall survival and overall mortality among the different groups were evaluated using the Kaplan-Meier method and Gray’s test. Results Patients were divided into groups according to whether they received radiotherapy or not. The median survival time of all 14,977 patients without RT was 20 months, neoadjuvant RT was 24 months and adjuvant RT was 23 months (p < 0.0001). Median survival time of 2089 stage I patients without RT was 56 months, significantly longer than those with RT regardless of neoadjuvant or adjuvant RT (no RT: 56 months vs adjuvant RT: 37 months vs neoadjuvant RT: 27 months, P = 0.0039). Median survival time of 12,888 stage II patients with neoadjuvant RT was 24 months, adjuvant RT 22 months, significantly prolonged than those without radiotherapy (neoadjuvant RT: 24 months vs adjuvant RT: 22 months vs no RT: 17 months, P<0.0001). Neoadjuvant RT (HR = 1.434, P = 0.023, 95% CI: 1.051–1.957) was independent risk factors for prognosis of stage I patients, and adjuvant RT (HR = 0.904, P < 0.001, 95% CI: 0.861–0.950) predicted better outcomes for prognosis of stage II patients by multivariate analysis. The risk of cancer-related death caused by neoadjuvant RT in stage I and no-RT in stage II patients were significantly higher. Conclusions The study identified a significant survival advantage for the use of adjuvant RT over surgery alone or neoadjuvant RT in treating stage II pancreatic cancer. RT was not associated with survival benifit in stage I patients.

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Analysis of radiotherapy impact on survival in resected stage I/II pancreatic cancer patients: a population-based study

10.21203/rs.3.rs-126795/v2 ◽

2021 ◽

Author(s):

Dong Han ◽

Fei Gao ◽

JinLong Liu ◽

Hao Wang ◽

Qi Fu

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Survival Time ◽

Median Survival ◽

Median Survival Time ◽

Population Based ◽

Stage I ◽

Stage Ii ◽

Resected Stage ◽

Risk Of Cancer

Abstract Background: The application of radiotherapy (RT) in pancreatic cancer remains controversial. Aim: The aim of the study was to evaluate the efficacy of radiotherapy (neoadjuvant and adjuvant radiotherapy) for resectable I/II pancreatic cancer. Methods: 14977 patients with pancreatic cancer were identified from SEER database from 2004 to 2015. Multivariate analyses were performed to determine factors including RT on overall survival. Overall survival and overall mortality among the different groups were evaluated using the Kaplan-Meier method and Gray’s test. Results: Patients were divided into groups according to whether they received radiotherapy or not. The median survival time of all 14977 patients without RT was 20 months, neoadjuvant RT was 24 months and adjuvant RT was 23 months (p < 0.0001) . Median survival time of 2089 stage I patients without RT was 56 months, significantly longer than those with RT regardless of neoadjuvant or adjuvant RT (no RT: 56 months vs adjuvant RT: 37 months vs neoadjuvant RT: 27 months, P=0.0039). Median survival time of 12888 stage II patients with neoadjuvant RT was 24 months, adjuvant RT 22 months, significantly prolonged than those without radiotherapy(neoadjuvant RT: 24 months vs adjuvant RT: 22 months vs no RT: 17 months, P＜0.0001). Neoadjuvant RT (HR=1.434, P=0.023, 95% CI: 1.051-1.957) was independent risk factors for prognosis of stage I patients, and adjuvant RT (HR=0.904, P < 0.001, 95% CI: 0.861-0.950) predicted better outcomes for prognosis of stage II patients by multivariate analysis. The risk of cancer-related death caused by neoadjuvant RT in stage I and no-RT in stage II patients were significantly higher. Conclusions: The study identified a significant survival advantage for the use of adjuvant RT over surgery alone or neoadjuvant RT in treating stage II pancreatic cancer. RT was not associated with survival benefit in stage I patients.

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Analysis of Radiotherapy Impact on Survival in Resected Stage I/ii Pancreatic Cancer Patients: A Population-based Study

10.21203/rs.3.rs-126795/v1 ◽

2020 ◽

Author(s):

Dong Han ◽

Fei Gao ◽

JinLong Liu ◽

Hao Wang ◽

Qi Fu

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Survival Time ◽

Median Survival ◽

Median Survival Time ◽

Population Based ◽

Stage I ◽

Stage Ii ◽

Resected Stage ◽

Risk Of Cancer

Abstract Background: The application of radiotherapy (RT) in pancreatic cancer remains controversial. The aim of the study was to evaluate the efficacy of radiotherapy (neoadjuvant and adjuvant radiotherapy) for resectable I/II pancreatic cancer. Methods: 14977 patients with pancreatic cancer were identified from SEER database from 2004 to 2015. Multivariate analyses were performed to determine factors including RT on overall survival. Overall survival and overall mortality among the different groups were evaluated using the Kaplan-Meier method and Gray’s test. Results: Patients were divided into groups according to whether they received radiotherapy or not. The median survival time of all 14977 patients without RT was 20 months, neoadjuvant RT was 24 months and adjuvant RT was 23 months (p < 0.0001) . Median survival time of 2089 stage I patients without RT was 56 months, significantly longer than those with RT regardless of neoadjuvant or adjuvant RT (no RT: 56 months vs adjuvant RT: 37 months vs neoadjuvant RT: 27 months, P=0.0039). Median survival time of 12888 stage II patients with neoadjuvant RT was 24 months, adjuvant RT 22 months, significantly prolonged than those without radiotherapy(neoadjuvant RT: 24 months vs adjuvant RT: 22 months vs no RT: 17 months, P＜0.0001). Neoadjuvant RT (HR=1.434, P=0.023, 95% CI: 1.051-1.957) was independent risk factors for prognosis of stage I patients, and adjuvant RT (HR=0.904, P < 0.001, 95% CI: 0.861-0.950) predicted better outcomes for prognosis of stage II patients by multivariate analysis. The risk of cancer-related death caused by neoadjuvant RT in stage I and no-RT in stage II patients were significantly higher. Conclusions: The study identified a significant survival advantage for the use of adjuvant RT over surgery alone or neoadjuvant RT in treating stage II pancreatic cancer. RT was not associated with survival benifit in stage I patients.

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Use of nab-paclitaxel and gemcitabine in pancreatic cancer without granulocyte colony-stimulating factor: A multicenter real-world experience

Journal of Oncology Pharmacy Practice ◽

10.1177/10781552211038677 ◽

2021 ◽

pp. 107815522110386

Author(s):

Angela Chen ◽

Vincent H Ha ◽

Sunita Ghosh ◽

Carole R Chambers ◽

Michael B Sawyer

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Median Overall Survival ◽

Progression Free Survival ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Free Survival ◽

Colony Stimulating Factors ◽

Median Progression Free Survival ◽

Stimulating Factor

Introduction The metastatic pancreatic adenocarcinoma clinical trial (MPACT) trial established gemcitabine (gem) and nab-paclitaxel (nab) as a standard treatment for pancreatic cancer utilizing granulocyte colony-stimulating factors to manage neutropenia. This was a challenge for jurisdictions that do not use granulocyte colony-stimulating factors in palliative settings. We developed dosage guidelines to dose modify gem and nab without granulocyte colony-stimulating factors. We undertook a retrospective review to determine the efficacy and safety of these dose adjustment guidelines in the real world. Methods A multi-centered, retrospective chart review was performed on pancreatic patients between December 1, 2014, and August 21, 2018. Provincial electronic medical health records were reviewed. Using Log-rank statistics we determined the patient's progression-free survival and overall survival. Results Of 248 patients, 209 met patient selection criteria. Patients were excluded if they were lost to follow-up, on gem alone prior to nab/gem combination therapy or did not receive nab or gem. Patients who received nab/gem as first-line therapy had a median progression-free survival of 6.3 months (95% CI, 5.1–7.4), and median overall survival of 11.1 months (95% CI, 9.5–12.8). Those who received gem/nab in the second line had a median progression-free survival of 4.6 months (95% CI, 2.8–6.5), and median overall survival of 19.3 months (95% CI, 12.6–26.0). Conclusions The patient’s progression-free survival and overall survival taking nab/gem using our dose modification algorithm were equivalent or superior to the MPACT trial's progression-free survival and overall survival. Gem/nab can be given by our dose modification scheme without granulocyte colony-stimulating factor.

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The Role of Nanoliposomal Irinotecan Plus Fluorouracil and Folinic Acid as Second-Line Treatment Option in Patients With Metastatic Pancreatic Ductal Adenocarcinoma

10.21203/rs.3.rs-489414/v1 ◽

2021 ◽

Author(s):

Se Jun Park ◽

Hyunho Kim ◽

Kabsoo Shin ◽

Tae Ho Hong ◽

Ja Hee Suh ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Adverse Events ◽

Pancreatic Ductal Adenocarcinoma ◽

Real World ◽

Median Overall Survival ◽

Ductal Adenocarcinoma ◽

Nanoliposomal Irinotecan ◽

Previously Treated ◽

Grade 3

Abstract BackgroundAccording to the NAPOLI-1 trial, nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (5-FU/LV) showed improved overall survival compared to fluorouracil alone for patients with metastatic pancreatic cancer who previously treated gemcitabine-based therapy. In that trial, Asian patients had frequent dose modification due to hematological toxicity. There has been limited information on the clinical benefit and toxicity of this regimen in a real-world setting. Herein, we assessed real-world experience of nal-IRI plus 5-FU/LV in patients with advanced pancreatic cancer after gemcitabine failure.MethodsWe conducted a single institution retrospective analysis of response, survival and safety in patients who had been treated with nal-IRI with 5-FU/LV. Patients with metastatic pancreatic ductal adenocarcinoma previously treated with gemcitabine-based therapy received nal-IRI (80mg/m2) with 5-FU/LV every 2 weeks. ResultsFifty-one patients received nal-IRI plus 5-FU/LV between January 2015 and December 2020. The median age was 67 years, and males were 58.8%. A total of 40 (78.4%) and 11 (21.6%) patients had received one and two lines of prior chemotherapy before enrollment, respectively. Median progression-free survival was 2.8 months (95% confidence interval [CI] 1.8-3.7) and median overall survival was 7.0 months (95% CI 6.0-7.9). Chemotherapy doses were reduced or delayed in 33 (64.7%) patients during the first 6 weeks and median relative dose intensity was 0.87. Thirty-six (70.6%) patients experienced any grade 3 or 4 adverse events. Most common grade 3 or 4 adverse event was neutropenia (58.8%) and most non-hematologic adverse events were under grade 2. Since the start of first-line chemotherapy, median overall survival was 16.3 months (95% CI 14.1-18.4).ConclusionsNal-IRI plus 5-FU/LV seems to be effective, with manageable toxicities, after gemcitabine-based treatment in patients with metastatic pancreatic ductal adenocarcinoma. Trial registration Retrospectively registered

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Results of Postoperative Radiotherapy in the Treatment of 29 Uterine Sarcoma Patients

Tumori Journal ◽

10.1177/030089160308900215 ◽

2003 ◽

Vol 89 (2) ◽

pp. 183-188 ◽

Cited By ~ 3

Author(s):

Durmuş Etiz ◽

Melahat Garipağaoğrlu ◽

Emine Elmas Etiz ◽

Faruk M Köse ◽

Fulya Kayikçioğrlu ◽

...

Keyword(s):

Overall Survival ◽

Postoperative Radiotherapy ◽

Menopausal Status ◽

Disease Free Survival ◽

Uterine Sarcoma ◽

Stage I ◽

Primary Tumors ◽

Local Recurrences ◽

Number Of Patients ◽

Disease Free

Aims and background The objective of this study was to evaluate the results of surgery combined with postoperative radiotherapy (RT) in patients with uterine sarcoma in order to describe the patterns of relapse and to define prognostic factors. Methods We report on 29 patients with uterine sarcoma (US) treated from 1980 to 1995; 18 patients with primary tumors were treated with surgery and adjuvant irradiation, while 11 patients with local recurrences (LR) after previous surgical resection received only radiotherapy. We evaluated the influence of stage, histology, grade, menopausal status, total radiation dose and brachytherapy on survival. Histological diagnosis was leiomyosarcoma in 13 patients (44.8%), endometrial stromal sarcoma in 10 patients (34.5%), and mixed mesodermal tumors in six patients (20.7%). Fifteen patients presented with stage I-II disease, three with stage III, and 11 with local recurrences. External pelvic RT was administered to all patients, in five patients combined with brachytherapy. The mean total dose was 54 Gy (SE 1.78). Univariate and multivariate analyses were carried out. Results Overall survival (OS) for the stage I-III group was 61.1% at two years and 33.3% at five years (median 29 months, SE 13.79). Disease-free survival (DFS) was 55.6% at two years and 33.3% at five years. Median DFS was 26 months (SE 14.85). In LR cases, median OS was only 10 months (SE 4.5). Multivariate analysis demonstrated that stage was the only prognostic factor after RT for US. Conclusions These data suggest that postoperative and/or salvage RT has a questionable impact on disease-free and overall survival because of the lack of homogeneity of stages in the series reported in the literature; it has, however, acceptable late side effects. Prospective multicenter trials including a statistically evaluable number of patients are necessary to further clarify the role of RT treatment programs for US.

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