Analysis of Fluorouracil-Based Adjuvant Chemotherapy and Radiation After Pancreaticoduodenectomy for Ductal Adenocarcinoma of the Pancreas: Results of a Large, Prospectively Collected Database at the Johns Hopkins Hospital

PurposeTo examine the efficacy of adjuvant chemoradiotherapy after pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma (PC) in patients undergoing resection at Johns Hopkins Hospital (JHH; Baltimore, MD).Patients and MethodsBetween August 30, 1993, and February 28, 2005, a total of 908 patients underwent PD for PC at JHH. A prospective database was reviewed to determine which patients received fluorouracil (FU) -based CRT. Excluded patients had metastatic disease, died 60 or fewer days after PD, received preoperative therapy, an experimental vaccine, adjuvant chemotherapy or radiation alone. The final cohort includes 616 patients.ResultsThe median follow-up was 17.8 months (interquartile range, 9.7 to 33.5 months). Overall median survival was 17.9 months (95% CI, 16.3 to 19.5 months). Groups were similar with respect to tumor size, nodal status, and margin status, but the CRT group was younger (P < .001), and less likely to present with a severe comorbid disease (P = .001). Patients with carcinomas larger than 3 cm (P = .001), grade 3 and 4 (P < .001), margin-positive resection (P = .001), and complications after surgery (P = .017) had poor long-term survival. Patients receiving CRT experienced an improved median (21.2 v 14.4 months; P < .001), 2-year (43.9% v 31.9%), and 5-year (20.1% v 15.4%) survival compared with no CRT. After controlling for high-risk features, CRT was still associated with improved survival (relative risk = 0.74; 95% CI, 0.62 to 0.89).ConclusionThese data suggest that adjuvant concurrent FU-based CRT significantly improves survival after PD for PC when compared with patients not receiving CRT. These data support the use of combined adjuvant CRT for PC.

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Long-term survival of patients receiving multimodality neoadjuvant therapy for resectable or borderline resectable pancreatic ductal adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.309 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 309-309

Author(s):

Kinsey McCormick ◽

Samuel H. Whiting ◽

Grace Gyurkey ◽

Wui-Jin Koh ◽

Mika Sinanan ◽

...

Keyword(s):

Neoadjuvant Therapy ◽

Survival Rates ◽

Ductal Adenocarcinoma ◽

Wound Complications ◽

R0 Resection ◽

Surgical Morbidity ◽

Borderline Resectable ◽

Term Survival

309 Background: While surgery offers the only chance for cure in localized PDA, outcomes remain poor for those who have undergone surgical resection (SR). Neoadjuvant therapy (NATx) has several advantages, including early treatment of micrometastatic disease, the potential for tumor downstaging, and improved selection of patients (pts) for surgery by excluding those with chemotherapy-refractory disease. Methods: We report long-term follow-up on consecutive pts with resectable or borderline resectable (R/BR) PDA treated at our institution with an off-protocol, but defined regimen of multi-modality NATx. Demographic, clinical and outcomes data were extracted from medical records. Overall survival (OS) and progression-free survival (PFS) were calculated by Kaplan-Meier analysis. Results: 16 pts with R/BR PDA were treated with NATx; median follow-up is now 41 months (mo) (7.9-91.5). The median age was 57, 50% were female, and all had an ECOG PS <2. Fourteen (88%) had BR disease, and 9 (56%) had radiographic evidence of nodal involvement. All pts received NA gemcitabine, docetaxel and capecitabine and 13 (81%) also received NA chemoradiotherapy with capecitabine +/- oxaliplatin. 14 pts (88%) underwent SR; of those, 11 (79%) received adjuvant chemotherapy. The median decline in CA19-9 over the course of NATx was 80%. An R0 resection was achieved in 11 pts (79%), and there were 2 pCR. To date, 12 pts have died, 4 are alive (including 2 with CA19-9 >1000 at dx), and 3 are without recurrence. The mPFS and mOS were 27.4 and 41 mo, respectively. 1- and 3-year survival rates were 94% and 56%, respectively. When analyses were restricted to pts who underwent SR, the mPFS and mOS were 29 mo and 47.8 mo, respectively. There were no surgery-related deaths. 3 pts had postoperative wound complications. Conclusions: In this series of mostly BR pancreatic cancer pts, treatment with multi-modality NATx resulted in an almost doubling of mOS when compared to historical controls. NATx was also safe, and did not increase surgical morbidity or mortality. Based on these encouraging results, a phase II protocol of multi-modality NATx for R/BR PDA was initiated and has now completed accrual.

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Impact of Lymph Node Involvement on Long-term Survival after R0 Pancreaticoduodenectomy for Ductal Adenocarcinoma of the Pancreas

Journal of Gastrointestinal Surgery ◽

10.1007/s11605-007-0113-3 ◽

2007 ◽

Vol 11 (3) ◽

pp. 350-356 ◽

Cited By ~ 50

Author(s):

Thomas Zacharias ◽

Daniel Jaeck ◽

Elie Oussoultzoglou ◽

Agnes Neuville ◽

Philippe Bachellier

Keyword(s):

Lymph Node ◽

Lymph Node Involvement ◽

Ductal Adenocarcinoma ◽

Term Survival ◽

Long Term Survival ◽

Node Involvement ◽

Adenocarcinoma Of The Pancreas

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Neoadjuvant and adjuvant, floxuridine, leucovorin, oxaliplatin, and docetaxel (FLOD) in patients with locally advanced operable gastroesophageal adenocarcinoma: A phase II study with pathologic responses and long term follow-up.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.4_suppl.124 ◽

2016 ◽

Vol 34 (4_suppl) ◽

pp. 124-124

Author(s):

Bach Ardalan ◽

Miriam Gombosh ◽

Dido Franceschi ◽

Eli Avisar ◽

Danny Yakoub ◽

...

Keyword(s):

Adjuvant Chemotherapy ◽

Neoadjuvant Therapy ◽

Residual Disease ◽

Locally Advanced ◽

Pathological Response ◽

Complete Pathological Response ◽

Term Survival ◽

Chemotherapy Patients

124 Background: A complete pathological response to neoadjuvant chemotherapy without the use of radiation has infrequently been reported in operable chemo-naïve stage III gastro esophageal adenocarcinoma patients. Methods: Twenty-nine patients were enrolled in this study. Neoadjuvant therapy consisted of Floxuridine, Leucovorin, Oxaliplatin, and Docetaxel and was administered in 2, four week cycles. Chemotherapy consisted on day one and day fifteen; Oxaliplatin, Docetaxel, FUDR, and Leucovorin. The latter two drugs were given concurrently over twenty four hours. On day eight, chemotherapy consisted of Docetaxel, FUDR, and Leucovorin. Following therapy, patients underwent surgical resection. Those patients having residual disease were offered adjuvant chemotherapy. Patients having a complete pathological response were not offered any further therapy. Results: Twenty-four out of twenty-nine patients completed neoadjuvant therapy and underwent esophagectomy. Two were declared inoperable after treatment. Three patients died prior to surgery. The median follow-up of all patients is now sixty months. The median overall survival has not been reached at sixty months. Five yr actual OS is 51%. Clinical response to neoadjuvant therapy was seen in (72.4%) patients. Complete pathological response to neoadjuvant therapy was seen in (16.7%) who are disease free at sixty month follow-ups. Seven out of twenty-four patients achieved partial pathological response (29.1%) and received adjuvant chemotherapy. They are all alive (100%). Eight patients achieved less than partial pathological response and received adjuvant chemotherapy, four out of eight are alive at sixty months (50%). Grade three and four toxicities were seen in sixteen out of twenty nine patients during neoadjuvant therapy. Grade three and four toxicities were seen in six out of fourteen patients during adjuvant therapy. Conclusions: Our chemotherapy regimen of Floxuridine, Leucovorin, Oxaliplatin and Docetaxel (FLOD) has resulted in long term survival in patients with adenocarcinoma of the esophagus. Clinical trial information: NCT00448760.

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The prognostic value of the lymph node ratio for local advanced gastric cancer patients with intensity-modulated radiation therapy and concurrent chemotherapy after radical gastrectomy in China

Radiation Oncology ◽

10.1186/s13014-020-01687-0 ◽

2020 ◽

Vol 15 (1) ◽

Author(s):

Yongqiang Yang ◽

Yifu Ma ◽

Xiaoyong Xiang ◽

Pengfei Xing ◽

Yongyou Wu ◽

...

Keyword(s):

Gastric Cancer ◽

Locoregional Recurrence ◽

Lymph Node Ratio ◽

Survival Rates ◽

Intensity Modulated Radiation Therapy ◽

Adjuvant Chemoradiotherapy ◽

Term Survival ◽

Node Ratio

Abstract Background Nearly 50% of new gastric cancer cases and gastric cancer-related deaths worldwide occur in China. No global consensus has been reached about the optimal management of locally advanced gastric cancer. Although the Guidelines for the Diagnosis and Treatment of Gastric Cancer from the National Health Commission of China, which has been updated three times since 2010, explicitly emphasize the necessity of adjuvant chemoradiation, few clinical institutions in China routinely adhere to the recommended radiotherapy guidelines. This study aimed to examine the efficacy, in terms of locoregional control and long-term survival, and the safety of adjuvant radiotherapy using intensity-modulated radiation therapy (IMRT) with concurrent and adjuvant fluoropyrimidine-based chemotherapy for gastric cancer. Methods This was a retrospective evaluation of 156 patients with high-risk gastric cancer who underwent adjuvant chemoradiotherapy between September 2008 and May 2019. The prescribed planning target volume median dose was 45 Gy in 1.8 Gy daily fractions, and all patients received concurrent and adjuvant fluoropyrimidine-based chemotherapy. Locoregional control, distant metastasis, and overall survival rates were estimated. Clinicopathological characteristics and patterns of failure were retrospectively reviewed to identify factors associated with survival and recurrence. Results The median follow-up duration was 56 months (range 3–130 months) for all patients. Of the patients, 11 (7.1%) were lost to follow-up, and 49 (31.4%) and 104 (66.7%) had stage II or III disease according to the eighth edition of the American Joint Committee on Cancer tumor-node-metastasis staging criteria. The frequencies of acute grade 3 or 4 gastrointestinal and hematological toxicity were 9.6% and 10.9%, respectively. In total, 152 patients (97.4%) completed the entire chemoradiation regimen. No toxicity-related deaths occurred. Nineteen patients (12.2%) had locoregional recurrence, 26 (16.7%) had distant metastases, and 12 (7.7%) had peritoneal metastasis. The overall survival (OS) rates were 83.5%, 65.0%, and 59.5%, while the disease-free survival rates were 75.1%, 61.0%, and 55.6% at 1, 3, and 5 years, respectively. In the multivariate analysis, age, pathological T stage and lymph node ratio (LNR) were found to be independent predictors of OS. Conclusion Postoperative concomitant IMRT and chemotherapy were well tolerated, with acceptable toxicities and encouraging locoregional tumor control and long-term survival. The LNR can be used as an important prognostic indicator for OS. Adjuvant chemoradiotherapy should be considered for all patients with a high risk of locoregional recurrence, especially in China.

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Nivolumab in patients with DNA mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) metastatic colorectal cancer (mCRC): Long-term survival according to prior line of treatment from CheckMate-142.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.554 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 554-554 ◽

Cited By ~ 13

Author(s):

Michael J. Overman ◽

Francesca Bergamo ◽

Raymond S. McDermott ◽

Massimo Aglietta ◽

Franklin Chen ◽

...

Keyword(s):

Term Survival ◽

Long Term Survival ◽

Dna Mismatch ◽

Long Term Follow Up ◽

Group A ◽

Grade 3 ◽

Group B ◽

Line Setting

554 Background: Nivolumab (NIVO) provided durable responses (ORR, 32% per central assessment) and disease control (DCR, 64%) in pre-treated pts with dMMR/MSI-H mCRC (NCT02060188; Overman MJ et al Lancet Oncol 2017). NIVO was approved in the US for pts with dMMR/MSI-H mCRC who progress after standard chemotherapy (SC) with a fluoropyrimidine (F), oxaliplatin (Ox), and irinotecan (Iri). Here we present long-term survival and outcomes by prior chemotherapy with NIVO in CheckMate-142. Methods: Pts with dMMR/MSI-H mCRC received NIVO 3 mg/kg Q2W. The primary endpoint was ORR per RECIST 1.1. Other endpoints were DCR, DOR, PFS, OS, and safety/tolerability. Results: Of 74 pts evaluated, 53 had received F, Ox and Iri (group A); 21 pts had ≤ 2 SC regimens (group B). Median follow-up was 21 mo. Efficacy by central assessment is shown in the Table. In the 74 pts, ORR was 34%; CRs increased from 3% in prior database lock (DBL) to 9%. Numerically higher responses were noted in group B vs group A (Table). Grade 3–4 TRAEs were reported in 20% (all pts), 25% (group A), and 10% (group B) of pts. No treatment-related deaths were reported. Conclusions: NIVO continued to provide clinically meaningful durable responses and long-term overall survival in pts with dMMR/MSI-H mCRC. Of note, CR rate increased with longer follow-up. No new safety signals were reported with long-term follow-up. Enhanced responses in pts with ≤ 2 SC regimens support ongoing evaluation of NIVO combinations in first-line setting. Clinical trial information: NCT02060188. [Table: see text]

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Pulmonary Adenocarcinoma Occurring 5 Years after Resection of a Primary Pancreatic Adenocarcinoma: A Relevant Differential Diagnosis

Case Reports in Oncological Medicine ◽

10.1155/2014/841907 ◽

2014 ◽

Vol 2014 ◽

pp. 1-4 ◽

Cited By ~ 1

Author(s):

R. F. Falkenstern-Ge ◽

M. Wohlleber ◽

M. Kimmich ◽

K. Huettl ◽

G. Friedel ◽

...

Keyword(s):

Pancreatic Adenocarcinoma ◽

Clinical Course ◽

Latency Period ◽

Pulmonary Adenocarcinoma ◽

Ductal Adenocarcinoma ◽

Term Survival ◽

Long Latency ◽

Localized Disease ◽

Adenocarcinoma Of The Pancreas

Ductal adenocarcinoma of the pancreas is a lethal disease. Surgical extirpation only offers the slim chance for long-term survival in localized disease. We report on a 73 year old female patient who initially underwent successful resection of pancreatic adenocarcinoma in May 2005. She was treated with adjuvant chemotherapy with gemcitabine. In October 2010 the patient noticed increasing dyspnea with haemoptysis. She was soon referred to our center. After the diagnosis of pulmonary adenocarcinoma with widespread metastasis, she was treated with systemic chemotherapy. For a period of next three years, she was treated with different chemotherapy regimens due to repeated episodes of tumor progression. To the best of our knowledge after reviewing the literature, this case represents an unusually clinical course with metachronous pulmonary adenocarcinoma arising after treatment of a primary pancreatic cancer after a long latency period.

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Intravascular lymphomatosis: a clinicopathologic study of 10 cases and assessment of response to chemotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.1994.12.12.2573 ◽

1994 ◽

Vol 12 (12) ◽

pp. 2573-2579 ◽

Cited By ~ 205

Author(s):

J A DiGiuseppe ◽

W G Nelson ◽

E J Seifter ◽

J K Boitnott ◽

R B Mann

Keyword(s):

Combination Chemotherapy ◽

Survival Duration ◽

Johns Hopkins Hospital ◽

Term Survival ◽

Long Term Survival ◽

Intravascular Lymphomatosis ◽

Clinicopathologic Study ◽

Response To Chemotherapy

PURPOSE We report a clinicopathologic study of 10 cases of intravascular lymphomatosis (IVL) seen at a single institution, and assess the response to chemotherapy in these patients, as well as those collected from a literature review. PATIENTS AND METHODS The clinical, pathologic, and immunophenotypic features of 10 cases of IVL diagnosed at the Johns Hopkins Hospital since 1977 were studied. Follow-up information was obtained in each case by consultation with the treating physician. In addition, cases of IVL reported previously in which patients were treated with chemotherapy and for which follow-up data were available at the time of publication were reviewed. RESULTS In the present series of 10 cases, the most common clinical features were fever of unknown origin (FUO), mental status changes, and rash. Diagnostic specimens were obtained from a variety of sources, including brain, skin, prostate, liver, kidney, and gallbladder. All of the four patients treated with combination chemotherapy are alive and two have achieved long-term survival (48 and 45 months, respectively); the remaining two are alive and in complete remission (CR) after short follow-up duration of 6 months. Among 35 patients reported in the literature who received chemotherapy (including four from this series), 43% attained a CR and were free of disease at the time of publication. None of the three patients in our series who received localized therapy (surgery with or without radiation therapy) is alive (mean survival duration, 9 months). For the three patients diagnosed at postmortem examination, the mean interval between onset of symptoms and death was 3 months, and disease was widespread. CONCLUSION These findings suggest that IVL represents a high-grade non-Hodgkin's lymphoma (NHL) with a propensity for systemic dissemination, and that CR and long-term survival may result in patients treated with aggressive combination chemotherapy.

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The actual 5-year survivors of pancreatic ductal adenocarcinoma based on real-world data

Scientific Reports ◽

10.1038/s41598-020-73525-y ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 1

Author(s):

Axel Bengtsson ◽

Roland Andersson ◽

Daniel Ansari

Keyword(s):

Pancreatic Cancer ◽

Pancreatic Ductal Adenocarcinoma ◽

Survival Data ◽

Multivariable Analysis ◽

Tnm Stage ◽

Ductal Adenocarcinoma ◽

Term Survival ◽

Long Term Survival

Abstract Survival data for pancreatic cancer are usually based on actuarial calculations and actual long-term survival rates are rarely reported. Here we use population-level data from the Surveillance, Epidemiology, and End Results program for patients with microscopically confirmed pancreatic ductal adenocarcinoma diagnosed from 1975 to 2011. A total of 84,275 patients with at least 5 years of follow-up were evaluated (follow-up cutoff date: December 31, 2016). Actual 5-year survival for pancreatic cancer increased from 0.9% in 1975 to 4.2% in 2011 in patients of all stages (p < 0.001), while in surgically resected patients, it rose from 1.5% to 17.4% (p < 0.001). In non-resected patients, the actual 5-year survival remained unchanged over the same time period (0.8% vs 0.9%; p = 0.121). Multivariable analysis of surgically resected patients diagnosed in the recent time era (2004–2011) showed that age, gender, grade, tumour size, TNM-stage and chemotherapy were significant independent predictors of actual 5-year survival, while age, grade and TNM-stage were significant independent predictors in non-resected patients. However, unfavourable clinicopathological factors did not preclude long-term survival. Collectively, our findings indicate that actual 5-year survival for pancreatic cancer is still below 5% despite improvement of survival for the subset of patients undergoing surgical resection.

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