Outcomes for patients with borderline resectable (BR) and locally advanced (LA) pancreatic cancer (PC) treated with induction FOLFIRINOX (FFX) +/- radiation (RT) followed by surgery compared to induction FFX followed by consolidative RT.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 437-437
Author(s):  
Michael Cecchini ◽  
Joseph Miccio ◽  
Jay Pahade ◽  
Jill Lacy ◽  
Ronald R Salem ◽  
...  

437 Background: Induction FFX for PC deemed either BR or LA at diagnosis provides an opportunity to downstage pts with the aim of an R0 surgery. The addition of RT after induction FFX may further downstage. However, there is a paucity of data regarding long-term survival for BR and LA patients successfully downstaged and resected. We performed a retrospective review of BR and LA PC treated with induction FFX +/- RT followed by surgery or consolidative RT at the Yale Cancer Center (YCC) to assess survival in these two cohorts. Methods: Clinical data was abstracted for pts with BR or LA PC who had surgery or received consolidative RT without surgery after induction FFX +/- RT at the YCC from 2010-2018. Surgical pts were re-reviewed by a radiologist to assess vascular involvement (BR vs. LA) using NCCN criteria. PFS and OS for surgery and consolidative RT were analyzed by the Kaplan-Meier method. Survival was compared via the log rank test. Results: 102 pts met inclusion criteria (BR=47, LA=55), 41 pts had surgery [BR=29/47 (62%) LA=12/55 (22%)] and 61 pts had consolidative RT [(BR= 18/47 (38%), LA= 43/55 (78%)] after induction FFX. 18 surgery pts received RT prior to resection and all surgery pts had R0 resection. Median follow up was 25 mo (range 5 – 97). Median PFS with surgery was 22 mo (95% CI 15 – 59) vs 14 mo (95% CI 10.9 – 20.1) with consolidative RT (p<0.001), while OS with surgery was 42 mo (95% CI 25-NR) vs 20 mo (95% CI 17-25) without surgery (p<0.001). For pts with ≥ 2 yr follow up, 12/22 (55%) surgery pts and 17/18 (94%) consolidative RT pts relapsed. For pts with ≥ 3 yr follow up, 6/12 (50%) surgery pts and 10/10 (100%) consolidative RT pts relapsed. 2 yr PFS and OS was 45% (95% CI 28-61) and 74% (95% CI 57 – 86) with surgery versus 15% (95% CI 7-27) and 40% (95% CI 26-53) with consolidative RT. Conclusions: Surgery was associated with a high R0 rate and prolonged PFS and OS compared to consolidative RT in pts with BR and LA PC after FFX +/- RT. However, survival benefit was not statistically significant when selecting only LA pts although numbers are limited.

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7529-7529
Author(s):  
B. Movsas ◽  
J. Moughan ◽  
C. Langer ◽  
M. Werner-Wasik ◽  
N. Nicolaou ◽  
...  

7529 Purpose: This analysis was conducted to address the potential antitumor effect of amifostine (AM) in NSCLC patients enrolled on RTOG-9801. The long-term survival results of RTOG-9801 are presented here. Methods: 243 patients (pts) with stage II/IIIAB NSCLC received induction paclitaxel (P) 225 mg/m2IV days 1, 22 and carboplatin (C) AUC 6 days 1, 22 and then concurrent weekly P (50 mg/m2) and C (AUC 2) and HRT (69.6 Gy at 1.2 Gy BID). Pts were randomly assigned to AM 500 mg IV 4x/week or no-AM during chemoradiation. Treatment differences for overall and disease-free survival (OS & DFS) were analyzed with the log-rank test; Gray's test was used for time to progression (TTP). Results: 118 pts were randomly assigned to receive AM and 121 to no-AM (4 pts were ineligible). The median follow-up for pts still alive is 52.3 months (mo) for the AM-arm and 58.3 mo for the no-AM arm (16.6 vs 17.9 for all pts). There are no significant differences in OS, DFS or TTP between arms. The median survival, 3-yr, and 5-yr OS are 17.1 mo, 27% and 17% (AM-arm) vs 18.4 mo, 28% and 16% (no-AM arm) (p=0.97). Grade 3/4/5 late-RT toxicities are similar (11%/3%/2% AM-arm vs 14%/4%/2% no-AM arm). Conclusion: While an earlier publication reported that amifostine did not reduce objective measures of severe esophagitis in RTOG-9801, patient-reported outcome analyses suggested a possible advantage to AM with decreased pain and swallowing symptoms (J Clin Oncol 23:2145–2154, 2005). This long-term follow-up analysis on survival shows no evidence of tumor radioprotection due to amifostine. The promising 5-yr OS suggests that induction paclitaxel/carboplatin (P/C) followed by concurrent RT and weekly low-dose P/C is comparable to other regimens using cisplatin doublets at higher dosages every 3–4 weeks. Research supported by NCI and Medimmune Oncology. No significant financial relationships to disclose.


2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 309-309
Author(s):  
Kinsey McCormick ◽  
Samuel H. Whiting ◽  
Grace Gyurkey ◽  
Wui-Jin Koh ◽  
Mika Sinanan ◽  
...  

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.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4046-4046 ◽  
Author(s):  
Megan Greally ◽  
Vivian E. Strong ◽  
Sam S. Yoon ◽  
Daniel G. Coit ◽  
Joanne F Chou ◽  
...  

4046 Background: Peri-op chemo (ctx) and surgery is a standard in the treatment of GC, based on the MAGIC (NEJM 2006; 355:11) and FLOT4 (J Clin Oncol 35:4004 [abstr]) studies. However, less than half of patients (pts) completed ctx in the MAGIC and FLOT4 studies, mainly from issues delivering post-op therapy. We assessed safety and feasibility of TNT, where all ctx is given pre-op. Methods: We reviewed GC pts who received TNT or peri-op ctx and had surgery; decision for TNT was by physician preference, based on clinical or radiographic benefit to justify completing ctx pre-op. Pt characteristics were compared using Fisher’s exact and Wilcoxon Rank Sum tests. Post-op length of stay (LOS) was calculated from date of surgery (DOS) to date of discharge and surgical morbidity was determined using the Clavien-Dindo classification. Progression free survival (PFS) and overall survival (OS) were calculated from DOS using Kaplan-Meier methods and compared between groups using the log-rank test. Results: 120 pts were identified, median age 63, 62.5% male, 98% ECOG 0/1. 93 pts (77.5%) received peri-op ctx and 27 (22.5%) received TNT. In peri-op pts, 19%, 43% and 38% received FLOT, platinum/fluropyrimidine (FP) and ECF/EOX respectively. In TNT pts, 56%, 37% and 7% received FLOT, platinum/FP and ECF/EOX respectively. 57% had subtotal gastrectomy. Surgical outcomes were similar between groups; median LOS was 6 and 7 days (p = 0.31) in peri-op and TNT pts respectively. There was no significant difference in Clavien Dindo grade I-II or III-IV morbidity between groups (p = 0.103). There were no deaths. TNT pts received higher proportions of planned treatment than peri-op ctx pts: 90% vs. 60% FP (0.001); 85% vs. 41% platinum ( < 0.001); 100% vs. 9% epirubicin (0.015) and 53% vs. 28% docetaxel (p = 0.169). At median follow-up of 19 months, median PFS and OS were not reached. There was no significant difference in PFS (p = 0.089) or OS (p = 0.59) between groups. Conclusions: TNT appears safe with no increase in post-op LOS or surgical morbidity observed. TNT pts had higher percentage drug delivery, suggesting potential benefit for administering all ctx before surgery. While longer survival follow-up is required, TNT may be considered in pts with locally advanced GC who are candidates for ctx.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4133-4133
Author(s):  
Grace E. Ryan ◽  
Janet E. Murphy ◽  
Christine A. Ulysse ◽  
Beow Y. Yeap ◽  
Jennifer Yon-Li Wo ◽  
...  

4133 Background: With the advent of FOLFIRINOX, the management of pancreatic cancer has undergone a profound change. There has been a shift to TNT with FOLFIRINOX followed by radiation and an attempt at surgical resection. Recent trials of TNT have demonstrated an ability to resect locally advanced (LA) and borderline resectable disease. There is a lack of prospective data demonstrating local and systemic recurrence rates after TNT. Methods: Two previously reported prospective clinical trials (Murphy JE, et al, JAMA Oncol 2018, 2019) of total neoadjuvant therapy were conducted between 2012 and 2018 for borderline and LA disease (NCT01591733, NCT01821729). Patients received FOLFIRINOX for 8 cycles. Upon restaging, patients with resolution of vascular involvement received short-course chemoradiotherapy (5 Gy x 5 with protons or 3 Gy x 10 w photons) with capecitabine (N=34). Patients with persistent vascular involvement received long-course chemoradiotherapy with capecitabine (N=56). All patients were considered for resection after TNT except for those patients with metastatic or unresectable disease. Results: 97 eligible patients were enrolled and started treatment on the borderline resectable (n = 48) and locally advanced (n= 49) study. 90 patients completed therapy. 80 patients were taken to the operating room. 61 patients had R0 resection and 5 patients had R1 resection. The table shows the distribution of local recurrences, local recurrences and metastatic disease, and metastatic disease alone. With a median follow-up of 5.2 years (range: 2.4-6.0), of the 61 R0 patients, 22 patients remained alive and free of disease, 7 patients had a local recurrence, 4 patients had locoregional and metastatic recurrence, and 24 patients had a metastatic recurrence. 3 patients who underwent R0 resection died of unrelated causes. Median survival for patients undergoing R0 resection is 43.8 months. Conclusions: Total neoadjuvant therapy for locally advanced and borderline resectable pancreatic cancer is potentially curable and may change the pattern of spread.[Table: see text]


2021 ◽  
Vol 14 (8) ◽  
pp. 705
Author(s):  
Hideki Houzen ◽  
Takahiro Kano ◽  
Kazuhiro Horiuchi ◽  
Masahiro Wakita ◽  
Azusa Nagai ◽  
...  

Reports on the long-term survival effect of edaravone, which was approved for the treatment of amyotrophic lateral sclerosis (ALS) in 2015 in Japan, are rare. Herein, we report our retrospective analysis of 45 consecutive patients with ALS who initially visited our hospital between 2013 and 2018. Of these, 22 patients were treated with edaravone for an average duration of 26.6 (range, 2–64) months, whereas the remaining patients were not treated with edaravone and comprised the control group. There were no differences in baseline demographics between the two groups. The primary endpoint was tracheostomy positive-pressure ventilation (TPPV) or death, and the follow-up period ended in December 2020. The survival rate was significantly better in the edaravone group than in the control group based on the Kaplan–Meier analysis, which revealed that the median survival durations were 49 (9–88) and 25 (8–41) months in the edaravone and control groups, respectively (p = 0.001, log-rank test). There were no serious edaravone-associated adverse effects during the study period. Overall, the findings of this single-center retrospective study suggest that edaravone might prolong survival in patients with ALS.


2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Xue-feng Leng ◽  
Kexun Li ◽  
Qifeng Wang ◽  
Wenwu He ◽  
Kun Liu ◽  
...  

Abstract   Esophageal cancer is the fourth primary cause of cancer-related death in the male in China.The cornerstone of treatment for resectable esophageal cancer is surgery. With the development of minimally invasive esophagectomy (MIE), it is gradually adopted as an alternative to open esophagectomy (OE) in real-world practice. The purpose of this study is to explore whether MIE vs. OE will bring survival benefits to patients with the advancement of treatment techniques and concepts. Methods Data were obtained from the Sichuan Cancer Hospital & Institute Esophageal Cancer Case Management Database (SCH-ECCM Database). We retrospective analyzed esophageal cancer patients who underwent esophagectomy from Jan. 2010 to Nov. 2017. Patients were divided into two groups: MIE and OE groups. Clinical outcome and survival data were compared using TNM stages of AJCC 8th edition. Results After 65.3 months of median follow-up time, 2958 patients who received esophagectomy were included. 1106 of 2958 patients (37.4%) were underwent MIE, 1533 of 2958 patients (51.8%) were underwent OE. More than half of the patients (56.7%, 1673/2958) were above stage III. The median overall survival (OS) of 2958 patients was 51.6 months (95% CI 45.2–58.1). The MIE group's median OS was 74.6 months compared to 42.4 months in the OE group (95% CI 1.23–1.54, P &lt; 0.001). The OS at 1, 3, and 5 years were 90%, 68%, 58% in the MIE group; 85%, 54%, 42% in the OE group,respectively (P&lt;0.001). Conclusion The nearly 8-year follow-up data from this single cancer center suggests that with the advancement of minimally invasive surgical technology, MIE can bring significant benefits to patients' long-term survival compared with OE. Following the continuous progression of minimally invasive surgery and establishing a mature surgical team, MIE should be encouraged.


2004 ◽  
Vol 22 (4) ◽  
pp. 640-647 ◽  
Author(s):  
Gunar K. Zagars ◽  
Matthew T. Ballo ◽  
Andrew K. Lee ◽  
Sara S. Strom

Purpose To determine the incidence of potentially treatment-related mortality in long-term survivors of testicular seminoma treated by orchiectomy and radiation therapy (XRT). Patients and Methods From all 477 men with stage I or II testicular seminoma treated at The University of Texas M.D. Anderson Cancer Center (Houston, TX) with postorchiectomy megavoltage XRT between 1951 and 1999, 453 never sustained relapse of their disease. Long-term survival for these 453 men was evaluated with the person-years method to determine the standardized mortality ratio (SMR). SMRs were calculated for all causes of death, cardiac deaths, and cancer deaths using standard US data for males. Results After a median follow-up of 13.3 years, the 10-, 20-, 30-, and 40-year actuarial survival rates were 93%, 79%, 59%, and 26%, respectively. The all-cause SMR over the entire observation interval was 1.59 (99% CI, 1.21 to 2.04). The SMR was not excessive for the first 15 years of follow-up: SMR, 1.30 (95% CI, 0.93 to 1.77); but beyond 15 years the SMR was 1.85 (99% CI, 1.30 to 2.55). The overall cardiac-specific SMR was 1.61 (95% CI, 1.21 to 2.24). The cardiac SMR was significantly elevated only beyond 15 years (P < .01). The overall cancer-specific SMR was 1.91 (99% CI, 1.14 to 2.98). The cancer SMR was also significant only after 15 years of follow-up (P < .01). An increased mortality was evident in patients treated with and without mediastinal XRT. Conclusion Long-term survivors of seminoma treated with postorchiectomy XRT are at significant excess risk of death as a result of cardiac disease or second cancer. Management strategies that minimize these risks but maintain the excellent hitherto observed cure rates need to be actively pursued.


2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Catherine Cheang ◽  
Pradeep Patil

Abstract   Circumferential resection margins (CRM) of an esophagectomy specimen for oesophageal cancer is a key prognostic factor of overall survival (OS). This retrospective study aims to compare OS of post-esophagectomy patients with CRM of &gt;1 mm (R0) and &lt; 1 mm (R1) with further subgroup analysis of locally advanced T3R0 vs T3R1 resection. Methods A total of 110 esophagectomies conducted between 2010 and 2020 were analysed. We recorded R stage based on pathological CRM &gt;1 mm (R0) or &lt; 1 mm (R1). OS was calculated from the day of surgery to day of death or otherwise censored. All patients underwent multimodal therapy including chemotherapy and similar pre-surgical and post-surgical management. 58 of these patients with pT3 stage esophageal cancer (EC) were selected and compared. Statistical analysis was carried out using SPSS. Results Of 110 patients, 78 (71.5%) patients had a R0 resection. Mean OS in R0 resections was 73 months (6 years) compared to 25.2 months (2 years) in R1 resection (p = 0.001). 58 of the 110 patients were pathological stage T3(pT3) despite downstaging with chemotherapy showing the burden of advanced disease. In patients with stage pT3 (n = 58), 32 patients were R0 resections, and 26 patients had R1 resections. Mean OS in T3R0 resections was 51.5 months compared to 28.5 months in T3R1 resection. OS comparison is significant (p = 0.011). Conclusion This study emphasizes the importance of clear CRM in all patients and especially in locally advanced pT3/T4a esophageal cancer in achieving long term survival. Techniques used to ensure a clear CRM such multimodality therapy combined with surgical radical resection concepts such as mesoesophagectomy should be employed.


2019 ◽  
Vol 104 (6) ◽  
pp. e4.3-e5
Author(s):  
V Gotta ◽  
A Atkinson ◽  
O Marsenic ◽  
M Pfister

BackgroundHemodialysis (HD) prescription significantly differs between pediatric and adult patients on maintenance HD, resulting in greater difference between prescribed and delivered HD dose.1,2 HD dose targets have formally not been evaluated for children, hence targets are mainly derived from adults (spKt/V >1.4; sp: single-pool model of urea distribution, K: urea clearance, t: duration of HD session, V: urea distribution volume). This analysis aimed to evaluate the relationship between delivered dialysis dose and survival in a large cohort of patients having started HD therapy in childhood.MethodsThis retrospective analysis included a cohort of patients < 30 years (y) on chronic HD treatment since childhood, having received thrice-weekly HD between 2004 and 2016 in outpatient DaVita dialysis centers. Survival while on HD (death from any cause) was investigated using Kaplan-Meier analysis stratified by age at start of HD (0–2, >2–6, >6–12, and >12–18 y), and three mean delivered dialysis dose levels (spKt/V < 1.4, 1.4–1.6, >1.6). Survival curves between subgroups were compared using the Log-rank test.Results1773 patients were included in the analysis, among n=34 having started HD at age of 0–2y, n=57 at >2–6y, n=244 at >6–12y, and n=1438 at >12–18y. Median follow-up on HD ranged between 1.5 (>2–6y) to 4.7 years (>6–12y) with maximal follow-up of 23 years. Death while on HD occurred in 1/34, 6/57, 26/244, and 101/1438 patients during recorded follow-up (p=0.075, n.s.). Patients with mean spKt/V < 1.4 had lower survival on HD than those with spKt/V >1.4–1.6 (p=0.019) and those with spKt/V >1.6 (p=0.035), with 10-year survival estimated to 75% (65.2–86.2%) versus 84.5% (78.5–90.9%) and 85.0% (80.8–89.5%), respectively.ConclusionsThis is the first study to report long term survival and its relationship with delivered HD dose in patients starting HD in childhood. Our results support targeting spKt/V(urea)>1.4 in children on chronic HD treatment.ReferencesGotta V, Marsenic O, Pfister M. Age- and weight-based differences in haemodialysis prescription and delivery in children, adolescents and young adults. Nephrol Dial Transplant 2018 Apr 18.Gotta V, Marsenic O, Pfister M. Understanding urea kinetic factors that enhance personalized hemodialysis prescription in children. ASAIO J 2019 Jan 14.Disclosure(s)M Pfister is a consultant at Quantitative Solutions a Certara Company. V Gotta has been supported for this project by the Research Fund for Junior Researchers, University of Basel, Switzerland. O Marsenic and A Atkinson declare no financial conflict of interest.


2019 ◽  
Vol 45 (2) ◽  
pp. 160-166 ◽  
Author(s):  
Farhad Farzaliyev ◽  
Hans-Ulrich Steinau ◽  
Halil-Ibrahim Karadag ◽  
Alexander Touma ◽  
Lars Erik Podleska

In this retrospective study, we analysed the long-term oncological and functional results after extended ray resection for sarcoma of the hand. Recurrence-free and overall survivals were calculated using the Kaplan–Meier method. The function of the operated hand was assessed with the Michigan Hand Questionnaire and compared with the contralateral side. Extended ray resection was performed in 25 out of 168 consecutive patients with soft-tissue and bony sarcomas of the hand. The overall 5- and 10-year, disease-specific survival rates were 86% and 81%, respectively. Local recurrences were observed in two patients. The Michigan Hand Questionnaire score for the affected hand at follow-up in nine patients was 82 points versus 95 for the healthy contralateral hands. We conclude that extended ray resection of osseous sarcomas breaking through the bone into the soft tissue or for soft tissue sarcomas invading bone is a preferable alternative to hand ablation when excision can be achieved with tumour-free margins. Level of evidence: III


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