Real-world outcomes in recurrent versus de novo metastatic pancreatic adenocarcinoma.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 387-387
Author(s):  
Laura Miotke ◽  
Christopher Duane Nevala-Plagemann ◽  
Jian Ying ◽  
Vaia Florou ◽  
Benjamin Haaland ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Proportional Hazards ◽  
De Novo ◽  
Recurrent Disease ◽  
Smoking Status ◽  
Single Agent ◽  
Clinic Visit ◽  
Cox Proportional Hazards ◽  
Ductal Adenocarcinoma ◽  
Significant Difference

387 Background: Optimal management of patients with recurrent pancreatic ductal adenocarcinoma (PDAC) is unknown. In the clinical trials that established a survival benefit with combination chemotherapy compared to single agent gemcitabine, patients with recurrent PDAC were either excluded (PRODIGE-4) or severely underrepresented (MPACT). In this study, we evaluated clinical outcomes of recurrent PDAC patients who receive systemic therapy and compared outcomes to patients with de novo advanced PDAC. Methods: Patients diagnosed with advanced PDAC between 2014 and October of 2019 were included using the nationwide Flatiron Health EHR-derived de-identified database. Patients without a clinic visit or initiation of treatment within 90 days of diagnosis were excluded. Patients were characterized as either de novo or recurrent PDAC based on stage at diagnosis and history of surgery. Patients with recurrent PDAC were further stratified based on time to recurrent disease. Overall survival (OS) was summarized within groups via Kaplan-Meier survival estimates, and compared between groups in the context of univariable and multivariable Cox proportional hazards models. The covariates adjusted for were gender, age, race, ECOG, smoking status, primary site, CA199, albumin, lymphocytes, neutrophils and monocytes. Results: We included 5170 patients with advanced PDAC, of which 1101 (21.3%) met criteria for recurrent disease. Patients with recurrent PDAC were more likely to have tumors in the head of the pancreas (71% vs 40%, p < 0.001) and had lower median CA19-9 (92.8 vs 617, p < 0.001), compared to the de novo PDAC patients. Median OS for the recurrent group was 10.8 m (95% CI = 9.9-11.7) vs. 7.3 m (95% CI = 7.0-7.7) in the de novo group (p < 0.001, both univariate and multivariable adjusted analyses). The most common first line palliative chemotherapy in patients with recurrent disease was Nab-paclitaxel plus gemcitabine (41%) or FOLFIRINOX (21%). Patients who recurred within six months of surgery (28%) had an OS of 10.0 m (95% CI = 8.7 -11) vs. 11.6 m (95% CI 10-12, p = 0.256) in those who recurred greater than six months from surgery. Conclusions: Our data suggest that patients with recurrent disease have significantly better survival outcomes compared to patients with de novo metastatic disease. We did not observe a significant difference in survival of patients who recurred within 6 months of resection compared to those who recurred greater than six months after surgery. These data support the inclusion of patients with recurrent PDAC in clinical trials, including those who develop recurrent disease within 6 months of surgery, with appropriate stratification for these variables.

No difference in reoperation rates for nonunions (operative nonunions) in posterior cervical fusions stopping at C7 versus T1/2: a cohort of 875 patients

2021 ◽  
pp. 1-7
Keyword(s):  
Proportional Hazards ◽  
Smoking Status ◽  
Incidence Rates ◽  
Cox Proportional Hazards ◽  
Adjacent Segment ◽  
Spine Registry ◽  
Age At Surgery ◽  
Significant Difference ◽  
Reoperation Rates

OBJECTIVE The challenges of posterior cervical fusions (PCFs) at the cervicothoracic junction (CTJ) are widely known, including the development of adjacent-segment disease by stopping fusions at C7. One solution has been to cross the CTJ (T1/T2) rather than stopping at C7. This approach may have undue consequences, including increased reoperations for symptomatic nonunion (operative nonunion). The authors sought to investigate if there is a difference in operative nonunion in PCFs that stop at C7 versus T1/T2. METHODS A retrospective analysis identified patients from the authors’ spine registry (Kaiser Permanente) who underwent PCFs with caudal fusion levels at C7 and T1/T2. Demographics, diagnoses, operative times, lengths of stay, and reoperations were extracted from the registry. Operative nonunion was adjudicated via chart review. Patients were followed until validated operative nonunion, membership termination, death, or end of study (March 31, 2020). Descriptive statistics and 2-year crude incidence rates and 95% confidence intervals for operative nonunion for PCFs stopping at C7 or T1/T2 were reported. Time-dependent crude and adjusted multivariable Cox proportional hazards models were used to evaluate operative nonunion rates. RESULTS The authors identified 875 patients with PCFs (beginning at C3, C4, C5, or C6) stopping at either C7 (n = 470) or T1/T2 (n = 405) with a mean follow-up time of 4.6 ± 3.3 years and a mean time to operative nonunion of 0.9 ± 0.6 years. There were 17 operative nonunions, and, after adjustment for age at surgery and smoking status, the cumulative incidence rates were similar between constructs stopping at C7 and those that extended to T1/T2 (C7: 1.91% [95% CI 0.88%–3.60%]; T1/T2: 1.98% [95% CI 0.86%–3.85%]). In the crude model and model adjusted for age at surgery and smoking status, no difference in risk for constructs extended to T1/T2 compared to those stopping at C7 was found (adjusted HR 1.09 [95% CI 0.42–2.84], p = 0.86). CONCLUSIONS In one of the largest cohort of patients with PCFs stopping at C7 or T1/T2 with an average follow-up of > 4 years, the authors found no statistically significant difference in reoperation rates for symptomatic nonunion (operative nonunion). This finding shows that there is no added risk of operative nonunion by extending PCFs to T1/T2 or stopping at C7.

scholarly journals Heterogeneous Definitions of Secondary Acute Myeloid Leukemia (AML) Yield Distinct Outcomes in Response to First-Line Treatment with Hypomethylating Agents (HMA) and Venetoclax (Ven)

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1216-1216
Author(s):  
Irena Tan ◽  
Matthew Schwede ◽  
Paul Phan ◽  
Raymond Yin ◽  
Tian Y Zhang ◽  
...  
Keyword(s):  
Real World ◽  
Proportional Hazards ◽  
De Novo ◽  
Hematologic Malignancy ◽  
Cox Proportional Hazards ◽  
Secondary Mutation ◽  
Mutation Profile ◽  
Significant Difference ◽  
De Novo Aml

Abstract Background: The combination of HMA and venetoclax is now standard of care for patients with AML who are not candidates for intensive chemotherapy. Elderly patients are more likely to have secondary AML (sAML), although the presence of an antecedent hematologic malignancy is often not apparent by history. Lindsley et al (Blood, 2015) showed that a somatic mutation in SRSF2, SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR, or STAG2 is &gt;95% specific for sAML and associated with worse outcomes. While outcomes with HMA/ven in patients meeting standard criteria for sAML have recently been reported (Pullarkat, ASCO 2021), we set out to conduct a real-world analysis of sAML patients receiving HMA/ven, including those with a secondary mutation profile (SMP) as described by Lindsley et al. We hypothesized that-when treated with HMA/ven-outcomes of patients with SMP may be most similar to those with de novo AML. Methods: Patients diagnosed with AML at Stanford Cancer Institute from 4/2017-3/2021 and treated with front-line HMA/ven were retrospectively reviewed. These included patients previously treated with HMA monotherapy for an antecedent hematologic malignancy and those who had previously received ≤ 3 cycles of HMA monotherapy for AML. Responses were classified per the modified International Working Group response criteria. Overall survival (OS) was assessed for all patients, and for patients who had a complete response (CR) or CR with incomplete hematologic recovery (CRi), duration of response (DoR) was also assessed. Statistical analyses were performed in R using the logrank test, with hazard ratios (HR) computed using the Cox proportional hazards model. For multivariate analyses, p-values for a specific variable were calculated using Cox proportional hazards regression. Results: 82 patients met criteria for inclusion; 78 had valid response assessments and 49 (62.8%) had achieved a CR or CRi at first response assessment. Median age was 72 years, with 3 patients younger than 60. 62 patients were male, median ECOG performance status (PS) was 1, median Charlson Comorbidity Index (CCI) was 6, median time to death or end of follow-up from the start of treatment was 366 days, and 58% of patients had adverse risk AML per ELN guidelines. Fig 1a demonstrates demographics for de novo, sAML (excluding SMP), and patients with SMP AML. 13 patients met criteria for AML-MRC, 23 patients had prior history of antecedent hematologic malignancy (18 with MDS or CMML, 5 with MDS/MPN overlap or MPN), 12 had tAML, and 20 patients possessed a SMP and did not meet criteria for the other three categories of sAML. 14 patients with de novo AML were characterized by the absence of any of the above factors. Patients with de novo AML were less likely to have adverse risk disease (29% vs. 64% in others) and had lower CCI scores (mean 5.1 vs. 6.2) but had no significant differences in age, gender, follow-up time, or PS. There was no statistically significant difference in rates of CR/CRi between the different subgroups or the different types of sAML; 69% of patients with de novo AML, 79% of SMP patients, and 57% of patients with other types of sAML achieved a CR or CRi. However, SMP patients had response durations and OS patterns similar to patients with de novo AML (Fig 1b and 1c), and when grouped with de novo patients, both DoR (HR = 3.5, p = 0.047, Fig 1d) and OS (HR = 2.1, p = 0.042, Fig 1e) were significantly longer than those of the sAML patients. Neither DoR nor OS were significantly longer when the SMP patients were grouped with sAML patients (respectively: HR = 3.3, p = 0.22, Fig 1f; HR = 1.5, p = 0.37, Fig 1g). In multivariate Cox proportional regression adjusting for age, ELN risk category, CCI, and PS, worse OS for sAML patients was maintained relative to the SMP and de novo patients (HR 2.9, p = 0.036), although the difference in DoR was no longer significant (HR 4.4, p= 0.10). Conclusions: Patients meeting standard definitions of sAML had worse outcomes than those with de novo AML when treated with HMA/ven in a retrospective, real-world analysis. Although a secondary mutation profile as described by Lindsley et al may be helpful in identifying patients with sAML, when treated with HMA/ven, patients with this profile have outcomes that align more closely with those of patients with de novo AML. Figure 1 Figure 1. Disclosures Mannis: Astex, Forty Seven Inc/Gilead, Glycomimetics, and Jazz Pharmaceuticals: Research Funding; AbbVie, Agios, Astellas Pharma, Bristol Myers Squibb, Genentech, MacroGenics, Pfizer, and Stemline: Consultancy.

scholarly journals Docetaxel vs. Novel Hormonal Agent for Upfront Management of De Novo Metastatic Hormone-Sensitive Prostate Cancer: A Comprehensive Report of a Single-Center Experience

2021 ◽  
Author(s):  
Sunny Guin ◽  
Bobby K. Liaw ◽  
Tomi Jun ◽  
Kristin Ayers ◽  
Bonny Patel ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prognostic Value ◽  
Proportional Hazards ◽  
De Novo ◽  
Standard Of Care ◽  
Cox Proportional Hazards ◽  
Post Treatment ◽  
Real World Data ◽  
Significant Difference ◽  
Hormone Sensitive

Abstract Background: Upfront docetaxel or novel hormonal agents (NHA) such as abiraterone and enzalutamide have become the standard of care for metastatic hormone sensitive prostate cancer (mHSPC). However, data comparing the efficacy of docetaxel and NHAs in this setting are limited.Patients and Methods: This was a retrospective cohort study of patients with de novo mHSPC treated with upfront docetaxel or an NHA between January 1, 2014 and April 30, 2019 within the Mount Sinai Health System. Clinical data were extracted from the medical record. The primary outcome was failure-free survival (FFS), defined as the time to next treatment. The primary predictor was treatment with docetaxel or NHA. FFS was compared between the two groups using the Kaplan Meier method and multivariable Cox proportional hazards models. We additionally assessed the prognostic value of post-treatment PSA.Results: We identified 94 de novo mHSPC patients; 52 and 42 treated with upfront docetaxel and NHAs, respectively. NHAs were associated with significantly longer FFS compared to docetaxel (20.7 vs. 10.1 months, p=0.023). In a multivariable model adjusting for demographics and clinical factors, docetaxel was independently associated with worse FFS compared to NHAs (HR 1.96, 95% CI 1.12−3.45, p=0.019). High metastasis burden patients had a significantly longer FFS with NHAs than docetaxel (25.12 vs. 9.63 months, p=0.014), while there was no significant difference in FFS among low metastasis burden patients (NHA 20.71 vs. Docetaxel 26.5 months, p=0.9). Regardless of treatment, lower post-treatment PSA levels were associated with improved FFS (58.95 vs. 11.57 vs. 9.4 months for PSA ≤0.2, 0.2-0.4, >0.4ng/ml, respectively; p<0.001) Conclusion: Comparative analysis of real-world data demonstrated longer FFS in de novo mHSPC treated with NHA compared to docetaxel. In addition, the depth of PSA response following combination treatment may hold prognostic value for mHSPC outcomes.

HENT1 tumor levels to predict survival of pancreatic ductal adenocarcinoma patients who received adjuvant gemcitabine and adjuvant 5FU on the ESPAC trials.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4006-4006 ◽  
Author(s):  
John P. Neoptolemos ◽  
William Greenhalf ◽  
Paula Ghaneh ◽  
Daniel H. Palmer ◽  
Trevor F. Cox ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Median Survival ◽  
Proportional Hazards ◽  
Predictive Marker ◽  
Tissue Microarrays ◽  
Cox Proportional Hazards ◽  
Ductal Adenocarcinoma ◽  
Nucleoside Transporter ◽  
Significant Difference ◽  
Group A

4006 Background: Some studies in patients with resected pancreatic cancer have suggested that expression of the human equilibrative nucleoside transporter (hENT1) may be predictive of improved survival from gemcitabine but these have either been based on retrospective non-randomized studies or in one study the principal treatment was chemoradiation. The samples collected from the adjuvant ESPAC1/3 randomized trials have provided a unique opportunity to assess to REMARK standards the therapeutic predictability of hENT1 in patients undergoing resection for pancreatic cancer. Methods: Tissue Microarrays (TMAs) were prepared using paraffin embedded tumor specimens from patients randomized to gemcitabine or 5FU/Folinic acid in the ESPAC-1 and -3 trials. Cores were given an H-Score depending on the level of staining with the 10D7G2 anti-hENT1 antibody. Groups were compared using Kaplan-Meier and Cox proportional hazards. Results: Scores were obtained for 176 gemcitabine treated and 176 5FU treated patients. The overall median H-Score was 48 and patients were classified as having high hENT1 if the mean score for their cores was above this. Median overall survival for gemcitabine treated patients was 23.4 (95% CI: 18.3, 26.0) months versus 23.5 (95% CI: 19.8, 27.3) months for 5FU treated patients (χ21 = 0.24, P = 0.623). In the gemcitabine group A significantly lower survival (χ21 = 9.87, P = 0.002) was noted with low hENT1 (median survival 17.1 (95% CI: 14.3, 23.8) versus 26.2 (95% CI: 21.2, 31.4) months). Median survival was 25.6 (95% CI: 20.1, 27.9) and 21.9 (95% CI: 16.0, 28.3) months respectively for high and low hENT1 in the 5FU group, a non-significant difference (χ21 = 0.83, P = 0.362). Multivariate analysis confirmed hENT1 expression as a predictive marker in gemcitabine (Wald χ2 = 7.10, P = 0.008) but not 5-fluorouracil (Wald χ2 =0.34, P = 0.560) groups. Conclusions: The study supports use of gemcitabine in patients with high tumor hENT1 expression and 5-fluorouracil in patients with low hENT1.

Bevacizumab beyond progression: Impact of subsequent bevacizumab retreatment in patients with ovarian, fallopian tube, and peritoneal cancer after progression.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5557-5557 ◽  
Author(s):  
Rebecca Ann Previs ◽  
Daniel Spinosa ◽  
Bryan M. Fellman ◽  
Amelia Lorenzo ◽  
Isabelle Mulder ◽  
...  
Keyword(s):  
Fallopian Tube ◽  
Proportional Hazards ◽  
Brca Mutation ◽  
Statistical Significance ◽  
Progression Free Survival ◽  
Clinic Visit ◽  
Cox Proportional Hazards ◽  
Peritoneal Cancer ◽  
Bevacizumab Treatment ◽  
Significant Difference

5557 Background: The Food and Drug Administration approved the use of bevacizumab for treatment of recurrent epithelial ovarian, fallopian tube, and primary peritoneal carcinoma (OC) in combination with chemotherapy. This study evaluates whether patients immediately retreated with bevacizumab derive benefit after progressing on a bevacizumab-containing regimen. Methods: This multi-institutional, retrospective study compared patients with high grade non-mucinous epithelial OC who received bevacizumab followed directly by another bevacizumab-containing treatment regimen to patients who received bevacizumab followed by a regimen that did not contain bevacizumab (or received no further treatment). All patient retreated with bevacizumab had stable or progressive disease on prior bevacizumab containing regimen. Progression free survival (PFS) and overall survival (OS) were estimated using Kaplan and Meier product-limit estimator and modeled via Cox proportional hazards regression. PFS was measured from the date of first bevacizumab treatment to the date of first progression, date of death or date of last clinic visit. OS was measured from the date of first bevacizumab treatment after progression to the date of death or date of last contact/clinic visit. Statistical significance was defined at the 0.05 level. Results: 275 patients received bevacizumab, of which 226 were evaluable; 102 received sequential treatment with bevacizumab and 124 received a bevacizumab containing regimen followed by a non-bevacizumab containing regimen at the time of progression. There was no significant difference between tumor grade, stage, or BRCA mutation. Median follow-up for all subjects was 17 months (range: 1.2-138.2 months). Median PFS was 10.21 months (95%CI: 8.05 - 11.79) and median OS was 22.14 months (95%CI: 17.1 – 27.4). Median PFS for patients who received bevacizumab without retreatment was 5.1 months (95%CI: 4.3 – 6.3) and 17.6 months (95%CI: 14.3 – 21.3) for patients who received sequential bevacizumab retreatment (p < 0.001). Median OS for patients who received bevacizumab without retreatment was 12.9 months (95%CI: 9.3 – 16.7) and 30.1 months (95%CI: 26.1 – 35.4) for patients who received sequential bevacizumab retreatment (p < 0.001). Conclusions: Our study shows OC patients treated with bevacizumab-containing regimens sequentially at the time of progression have significantly prolonged survival outcomes compared to those patients who received no re-treatment with bevacizumab.

Real-world overall survival of patients diagnosed with recurrent versus de novo metastatic pancreatic ductal adenocarcinoma (PDAC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16250-e16250
Author(s):  
Eileen Mary O'Reilly ◽  
Kenneth H. Yu ◽  
Neil Lamarre ◽  
Andy Surinach ◽  
Paul Cockrum
Keyword(s):  
Overall Survival ◽  
Real World ◽  
Proportional Hazards ◽  
De Novo ◽  
Relative Survival ◽  
Cox Proportional Hazards ◽  
Stage I ◽  
Ductal Adenocarcinoma ◽  
Similar Proportion ◽  
Metastatic Setting

e16250 Background: PDAC is a lethal malignancy which accounted for the third most cancer related deaths in 2020. Patients (pts) who are initially diagnosed with stage I-III PDAC have a 5-year relative survival of 13.3 – 39.4%; those with metastatic disease at diagnosis have a 5-year relative survival of 2.9%. Limited data are published comparing the outcomes of pts with stage I-III who develop metastases (recurrent) compared to pts with de novo mPDAC (de novo). This analysis seeks to compare demographic, clinical characteristics, and survival outcomes of pts with recurrent versus de novo mPDAC in a community oncology setting. Methods: Using the Flatiron Health database, a retrospective observational study was conducted abstracting deidentified data from ≥280 US cancer clinics. Pts with mPDAC diagnosed from 01/2016 to 08/2020 with a known stage at initial diagnosis were included. Pts were stratified based on initial stage at diagnosis. Median overall survival (OS) from time of metastasis was derived using Kaplan-Meier analysis. Unadjusted and multivariable Cox proportional hazards models were used to compare survival between recurrent and de novo cohorts. Results: N = 6,543 pts analyzed; 70.1% (n = 4,586) had de novo mPDAC and 29.9% (n = 1,957) had recurrent mPDAC. Median age at time of metastasis was similar for both cohorts: 69 years (IQR: 62 – 76). The most common site of primary tumor location was head for both cohorts (recurrent mPDAC: 69.8%; de novo mPDAC: 40.3%). Approximately 45% of pts with recurrent mPDAC underwent a Whipple procedure (pre diagnosis of metastasis). A similar proportion of pts in both cohorts received treatment in the metastatic setting (recurrent mPDAC: 74.3%; de novo mPDAC: 77.3%). Pts with recurrent mPDAC had a longer median OS compared to the de novo cohort: 8.0 months (95% CI: 7.5 – 8.6) versus 6.1 (95% CI: 5.7 – 6.4) [unadjusted hazard ratio (HR): 0.79 (95% CI: 0.74 – 0.84); adjusted HR: 0.73 (0.68 – 0.78), p < 0.0001]. Conclusions: The results of this real-world study indicate that pts with recurrent mPDAC are more likely to have a head primary and to experience longer OS from time of metastasis than those with de novo mPDAC. These data suggest stratification for clinical trial enrollment for recurrent vs de novo is necessitated.

scholarly journals Pulmonary Sclerosing Pneumocytoma and Mortality Risk

2021 ◽  
Author(s):  
So Jeong Kim ◽  
Hye-Rin Kang ◽  
Chun Geun Lee ◽  
Seung Ho Choi ◽  
Yeon Wook Kim ◽  
...  
Keyword(s):  
Literature Review ◽  
Surgical Resection ◽  
Mortality Risk ◽  
Proportional Hazards ◽  
Smoking Status ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Kaplan Meier ◽  
Significant Difference ◽  
All Cause Mortality

Abstract Background: Surgical resection is recommended in all patients with pulmonary sclerosing pneumocytoma (PSP). However, no comparative study has demonstrated that surgical resection leads to improved outcomes. We aimed to compare all-cause mortality between patients with PSP who underwent surgery or did not and those without PSP.Methods: Participants aged ≥18 years who had pathologically diagnosed PSP between 2001 to 2018, at 3 hospitals were included. Randomly selected (up to 1:5) age-, sex-, and smoking status-matched controls were included. Mortality was compared using Kaplan–Meier estimates and Cox proportional hazards regression models. Literature review of studies reporting PSP was also conducted.Results: This study included 107 patients with PSP (surgery:non-surgery, 80:27) and 520 matched controls. There were no cases of lymph node or distant metastasis, recurrence, or mortality from PSP. No significant difference in all-cause mortality risk was observed between the PSP surgery, PSP non-surgery, and non-PSP groups (log rank test P=0.78) (PSP surgery vs. non-PSP: adjusted hazards ratio [aHR], 1.80; 95% confidence interval [CI], 0.22-14.6; PSP non-surgery vs. non-PSP: aHR, 0.77; 95% CI, 0.15-3.86; PSP surgery vs. PSP non-surgery: aHR, 2.35; 95% CI, 0.20-28.2). In the literature review, we identified 3,469 patients with PSP from 355 studies. Only 1.33% of these patients reported metastasis, recurrence, or death.Conclusion: All-cause mortality did not differ between patients with PSP and those without, irrespective of undergoing surgery. Our study and the literature review suggest that PSP has less impact on increased mortality risk.

scholarly journals Drug Repurposing Opportunities in Pancreatic Ductal Adenocarcinoma

2021 ◽  
Vol 14 (3) ◽  
pp. 280
Author(s):  
Rita Rebelo ◽  
Bárbara Polónia ◽  
Lúcio Lara Santos ◽  
M. Helena Vasconcelos ◽  
Cristina P. R. Xavier
Keyword(s):  
Clinical Trials ◽  
Drug Development ◽  
Pancreatic Ductal Adenocarcinoma ◽  
De Novo ◽  
Drug Repurposing ◽  
Metastatic Tumor ◽  
Therapeutic Options ◽  
Ductal Adenocarcinoma ◽  
Clinical Indication ◽  
Novel Treatments

Pancreatic ductal adenocarcinoma (PDAC) is considered one of the deadliest tumors worldwide. The diagnosis is often possible only in the latter stages of the disease, with patients already presenting an advanced or metastatic tumor. It is also one of the cancers with poorest prognosis, presenting a five-year survival rate of around 5%. Treatment of PDAC is still a major challenge, with cytotoxic chemotherapy remaining the basis of systemic therapy. However, no major advances have been made recently, and therapeutic options are limited and highly toxic. Thus, novel therapeutic options are urgently needed. Drug repurposing is a strategy for the development of novel treatments using approved or investigational drugs outside the scope of the original clinical indication. Since repurposed drugs have already completed several stages of the drug development process, a broad range of data is already available. Thus, when compared with de novo drug development, drug repurposing is time-efficient, inexpensive and has less risk of failure in future clinical trials. Several repurposing candidates have been investigated in the past years for the treatment of PDAC, as single agents or in combination with conventional chemotherapy. This review gives an overview of the main drugs that have been investigated as repurposing candidates, for the potential treatment of PDAC, in preclinical studies and clinical trials.

scholarly journals Pre-diagnosis neutrophil-to-lymphocyte ratio and mortality in individuals who develop lung cancer

2021 ◽  
Author(s):  
Laurie Grieshober ◽  
Stefan Graw ◽  
Matt J. Barnett ◽  
Gary E. Goodman ◽  
Chu Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Proportional Hazards ◽  
Smoking Status ◽  
Cox Proportional Hazards ◽  
Neutrophil To Lymphocyte Ratio ◽  
Blood Draw ◽  
Lymphocyte Ratio ◽  
Cox Proportional Hazards Models ◽  
Inflammatory Profile ◽  
Heavy Smokers

Abstract Purpose The neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation that has been reported to be associated with survival after chronic disease diagnoses, including lung cancer. We hypothesized that the inflammatory profile reflected by pre-diagnosis NLR, rather than the well-studied pre-treatment NLR at diagnosis, may be associated with increased mortality after lung cancer is diagnosed in high-risk heavy smokers. Methods We examined associations between pre-diagnosis methylation-derived NLR (mdNLR) and lung cancer-specific and all-cause mortality in 279 non-small lung cancer (NSCLC) and 81 small cell lung cancer (SCLC) cases from the β-Carotene and Retinol Efficacy Trial (CARET). Cox proportional hazards models were adjusted for age, sex, smoking status, pack years, and time between blood draw and diagnosis, and stratified by stage of disease. Models were run separately by histotype. Results Among SCLC cases, those with pre-diagnosis mdNLR in the highest quartile had 2.5-fold increased mortality compared to those in the lowest quartile. For each unit increase in pre-diagnosis mdNLR, we observed 22–23% increased mortality (SCLC-specific hazard ratio [HR] = 1.23, 95% confidence interval [CI]: 1.02, 1.48; all-cause HR = 1.22, 95% CI 1.01, 1.46). SCLC associations were strongest for current smokers at blood draw (Interaction Ps = 0.03). Increasing mdNLR was not associated with mortality among NSCLC overall, nor within adenocarcinoma (N = 148) or squamous cell carcinoma (N = 115) case groups. Conclusion Our findings suggest that increased mdNLR, representing a systemic inflammatory profile on average 4.5 years before a SCLC diagnosis, may be associated with mortality in heavy smokers who go on to develop SCLC but not NSCLC.

scholarly journals Survival rates and prognostic factors in right- and left-sided colon cancer stage I–IV: an unselected retrospective single-center trial

2021 ◽  
Author(s):  
Claudius E. Degro ◽  
Richard Strozynski ◽  
Florian N. Loch ◽  
Christian Schineis ◽  
Fiona Speichinger ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Blood Level ◽  
Proportional Hazards ◽  
Survival Rates ◽  
Cox Proportional Hazards ◽  
Stage I ◽  
Cancer Stage ◽  
Single Center ◽  
Significant Difference

Abstract Purpose Colorectal cancer revealed over the last decades a remarkable shift with an increasing proportion of a right- compared to a left-sided tumor location. In the current study, we aimed to disclose clinicopathological differences between right- and left-sided colon cancer (rCC and lCC) with respect to mortality and outcome predictors. Methods In total, 417 patients with colon cancer stage I–IV were analyzed in the present retrospective single-center study. Survival rates were assessed using the Kaplan–Meier method and uni/multivariate analyses were performed with a Cox proportional hazards regression model. Results Our study showed no significant difference of the overall survival between rCC and lCC stage I–IV (p = 0.354). Multivariate analysis revealed in the rCC cohort the worst outcome for ASA (American Society of Anesthesiologists) score IV patients (hazard ratio [HR]: 16.0; CI 95%: 2.1–123.5), CEA (carcinoembryonic antigen) blood level > 100 µg/l (HR: 3.3; CI 95%: 1.2–9.0), increased lymph node ratio of 0.6–1.0 (HR: 5.3; CI 95%: 1.7–16.1), and grade 4 tumors (G4) (HR: 120.6; CI 95%: 6.7–2179.6) whereas in the lCC population, ASA score IV (HR: 8.9; CI 95%: 0.9–91.9), CEA blood level 20.1–100 µg/l (HR: 5.4; CI 95%: 2.4–12.4), conversion to laparotomy (HR: 14.1; CI 95%: 4.0–49.0), and severe surgical complications (Clavien-Dindo III–IV) (HR: 2.9; CI 95%: 1.5–5.5) were identified as predictors of a diminished overall survival. Conclusion Laterality disclosed no significant effect on the overall prognosis of colon cancer patients. However, group differences and distinct survival predictors could be identified in rCC and lCC patients.

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