Impact of an inter-professional clinic on pancreatic cancer outcomes: The Princess Margaret Cancer Centre (PM) experience.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 444-444
Author(s):  
Hamzeh Albaba ◽  
Anna Dodd ◽  
Rebecca M. Prince ◽  
Kyaw Lwin Aung ◽  
David W. Hedley ◽  
...  

444 Background: Patients with pancreatic ductal adenocarcinoma (PDAC) have limited treatment options. Management of complex symptoms and psychosocial implications requires an interprofessional approach as prognosis is often measured in months. A multidisciplinary approach has been associated with improvement in clinical outcomes including survival. We aimed to evaluate the impact of an inter-professional approach for PDAC patients at the Wallace McCain Centre for Pancreatic Cancer (WMCPC) at PM on their management and clinical outcomes. Methods: We undertook retrospective review of all patients with PDAC seen at PM two years before (July ‘12 – June ‘14) and two years after (July ‘14 – June ‘16) establishment of the WMCPC. Standard therapies (surgical approach, chemotherapy, radiation therapy) were the same during both time periods. Comparison of overall survival (OS), stage at diagnosis, surgical outcomes, waiting times, and proportion seen by social worker, dietician and clinical nurse specialist (CNS) was explored with descriptive statistic and survival analysis. Results: A total of 993 patients were reviewed; 482 patients pre- and 511 patients post-WMCPC. Age (median 67 yrs), sex (54% men) and stage III/IV (52%) were similar in both groups. There was a trend to improved OS in the post-WMCPC group (9.6 vs. 10.9 m; p = 0.055); multivariable analysis found a significant improvement in OS after adjustment for performance status and stage (p = 0.023; HR 0.84, 95% CI 0.72-0.98). Rate of R0 versus R1/R2 resection for curative surgery (n = 264, 28%) was similar in both groups. Time from referral to first clinic visit significantly decreased from 13.4 to 8.8 days in the post-WMCPC group (p < 0.001) as did time from first clinic appointment to diagnostic biopsy (25.9 vs. 16.9 days, p = 0.022). Patients in the post-WMCPC were more frequently seen by a social worker, dietician or CNS (8% vs. 38%, 9% vs. 35% and 31% vs. 50% respectively, p < 0.001). Conclusions: Establishment of an interprofessional clinic for the treatment of PDAC patients at PM has streamlined diagnosis, aided symptom management and improved overall survival. This has implications for planning care delivery models and proves the value of this intervention.

2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Ujjwal M Mahajan ◽  
Elisabetta Goni ◽  
Enno Langhoff ◽  
Qi Li ◽  
Eithne Costello ◽  
...  

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.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19121-e19121
Author(s):  
Ravi Parikh ◽  
Angel Cronin ◽  
David E. Kozono ◽  
Geoffrey R. Oxnard ◽  
Raymond H. Mak ◽  
...  

e19121 Background: Although palliative chemotherapy is the standard of care for metastatic NSCLC, somepatients with oligometastatic disease may benefit from aggressive local therapy. We investigated factors associated with greater survival among patients diagnosed with a solitary metastatic lesion. Methods: We identified patients diagnosed with stage IV NSCLC who presented with a solitary metastatic lesion based on PET and MRI and who were prospectively consented and enrolled in our institutional database from 2002-2011. Univariable and multivariable Cox proportional hazards models were used to analyze factors associated with overall survival among this cohort. Results: We identified 110 patients (10.7% of stage IV patients) meeting our inclusion criteria. Median age at diagnosis was 61 years, 50% of patients were female, 66% had adenocarcinoma histology, and 35% had N0-1 disease. Median survival from diagnosis was 18.7 months, with a median followup of 31.5 months. On univariable analysis, greater overall survival was associated with ECOG performance status 0-1 vs 2+ (median 21.5 months vs 12.6 months, HR 0.32, p<0.01); weight loss <2 vs >2 kg (22.4 vs 13.8, HR 0.56, p=0.03); and N stage 0-1 vs 2-3 (32.0 vs 17.6, HR 0.52, p=0.02). Adenocarcinoma vs non-adenocarcinoma histology (22.9 vs 13.8, HR 0.65, p=0.07) was borderline significant. Age, gender, race, current smoking, size of primary tumor, and metastatic organ were not significantly associated with survival. On multivariable analysis, adenocarcinoma histology (HR= 0.58, p=0.06); N stage 0-1 (HR= 0.43, p=0.01); and weight loss <2 kg (HR 0.53, p=0.03) were associated with greater overall survival. Conclusions: Select patient and tumor characteristics may predict for improved survival among patients with oligometastatic NSCLC. Future studies will evaluate the impact of aggressive local therapy in these patients.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4126-4126
Author(s):  
Pranav Murthy ◽  
Mazen S Zenati ◽  
Samer S. AlMasri ◽  
Aatur D. Singhi ◽  
Annissa DeSilva ◽  
...  

4126 Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by chronic inflammation and a tolerogenic immune response. Neutropenia is a common side effect of cytotoxic chemotherapy, managed with administration of recombinant granulocyte-colony stimulating factor (G-CSF, Filgrastim). The interleukin 17 – G-CSF – neutrophil extracellular trap (NET) axis promotes oncogenesis and progression of PDAC, inhibiting adaptive immunity. We evaluated the impact of G-CSF administration during neoadjuvant therapy (NAT) on oncologic outcomes in patients with operable pancreatic cancer. Methods: A retrospective review of all patients with localized PDAC treated with NAT prior to pancreatic resection between 2014 – 2020 was completed at a single institution. G-CSF administration, type, and dose were collected from inpatient and outpatient medical records. Results: Of 351 patients treated, 138 (39%) received G-CSF during NAT with a median follow-up of 45.8 months. Patients who received G-CSF were younger (64.0 vs 66.7, p = 0.008), had lower BMI (26.5 vs 27.9, p = 0.021), and were more likely to receive 5-FU based chemotherapy (42% vs 28.2%, p < 0.0001), NAT dose reduction (40.6% vs 25.4%, p = 0.003), or experience febrile neutropenia (8.7% vs 3.3%, p = 0.029). No differences were observed in baseline or pathologic tumor staging. In patients who received G-CSF, 130 (94%) received Pegfilgrastim with a median cumulative dose of 12 mg (IQR 6-12). Patients who received G-CSF were more likely to have an elevated post-NAT neutrophil to lymphocyte ratio (45% vs 29.6%, p = 0.004) and systemic immune-inflammation index (39.5% vs 29.6%, p = 0.061). Receiving G-CSF was an independent predictor of perineural invasion (HR 2.4, 95 CI [1.08, 5.5], p = 0.031) and margin positive resection (HR 1.69, 95 CI [1.01, 2.83], p = 0.043). Patients who received G-CSF had decreased overall survival compared to patients who did not receive G-CSF (median OS: 29.2 vs 38.7 months, p = 0.0001). Receiving G-CSF during NAT was an independent negative predictor of progression free (HR 1.38, 95 CI [1.04, 1.83], p = 0.022) and overall survival (HR 2.02, 95 CI [1.45, 2.79], p < 0.0001). In a subset of patients with available pre- and post-NAT serum specimens (n = 28), G-CSF administration resulted in an increased number of citrullinated histone H3 complexes following NAT (+1378±1502 vs -300.7±1147 pg/ml, p = 0.007), indicative of enhanced peripheral NET formation. Conclusions: In patients with localized PDAC receiving NAT prior to surgical extirpation, G-CSF administration is associated with worse oncologic outcomes and should be administered with caution. Prospective randomized as well as confirmatory clinical studies are in order.


2020 ◽  
Vol 14 ◽  
pp. 117955492091940
Author(s):  
Basem Azab ◽  
Francisco Igor Macedo ◽  
David Chang ◽  
Caroline Ripat ◽  
Dido Franceschi ◽  
...  

Background: We aimed to study the impact of neoadjuvant chemotherapy to surgery (NCT-S) interval and neoadjuvant radiotherapy (NRT) on pathological complete response (pCR) and overall survival (OS) in pancreatic cancer (pancreatic ductal adenocarcinoma [PDAC]). Methods: National Cancer Data Base (NCDB)–pancreatectomy patients who underwent NCT/NRT were included. The NCT-S interval was divided into time quintiles in weeks: 8 to 11, 12 to 14, 15 to 19, 20 to 29, and >29 weeks. Results: A total of 2093 patients with NCT were included with median follow-up of 74 months and 71% NRT. The pCR rate was 2.1% with higher median OS compared with non-pCR (41 vs 19 months, P = .03). The pCR rate increased with longer NCT-S interval (quintiles: 1%, 1.6%, 1.7%, 3%, and 6%, P < .001, respectively). In logistic regression, NRT (odds ratio [OR] = 2.5, 95% confidence interval [CI]: 1.1-6.1, P = .03) and NCT-S >29 weeks (OR = 6.1, 95% CI = 2.02-18.50, P < .001) were predictive of increased pCR. The prolonged NCT-S interval and pCR were independent predictors of OS, whereas NRT was not. Conclusions: Longer NCT-S interval and pCR were independent predictors of improved OS in patients with PDAC. The NRT predicted increased pCR but not OS.


2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 303-303 ◽  
Author(s):  
Mairead Geraldine McNamara ◽  
Priya Aneja ◽  
Lisa W Le ◽  
Anne M Horgan ◽  
Elizabeth McKeever ◽  
...  

303 Background: BTCs include intrahepatic (IHC), hilar, distal bile duct (DBD), and gallbladder carcinoma (GBC). Statins, aspirin and metformin may have antineoplastic properties. The impact of their use on overall survival and the recurrence free survival of patients who had curative resection of BTC has not been evaluated. Methods: Baseline demographics and use of statins, aspirin or metformin at diagnosis were evaluated in 913 patients with BTC from 01/87 - 07/13 treated at Princess Margaret Cancer Center, Toronto. Their prognostic significance for recurrence free and overall survival was determined using a Cox proportional hazards model. Results: The median age at diagnosis for the entire cohort was 65.7 years (range 23.7-93.7). 795 patients had a performance status < 2 and 461 (50.5%) were male. The primary site was GBC in 310 (34%) patients, DBD in 212 (23%), IHC in 200 (22%) and hilar in 191 (21%). Curative surgical resection was performed in 355 (39%) patients. Among the entire cohort of 913 patients, 151 (16.5%) reported statin use at diagnosis. Atorvastatin was the statin used in 55% of patients. 146 (16%) reported aspirin use and 81 (9%) reported metformin use at diagnosis. Age (p=0.05, p<0.01), and stage (p<0.001, p<0.001) were prognostic on multivariable analysis for recurrence free and overall survival respectively. GBC (p=0.01), DBD (p<0.01) primary and performance status ≥ 2 (p < 0.0001) were also prognostic for overall survival. Recurrence free and overall survival among statin users and nonusers was similar (Hazard Ratio (HR) 1.07, 95% confidence interval (CI) 0.78-1.48, p=0.68) and (HR 0.84 (95% CI 0.67-1.05, p=0.12) respectively. Recurrence free and overall survival among aspirin users and nonusers was similar (HR 0.91, 95% CI 0.64-1.29, P=0.58) and (HR 0.98 (95% CI 0.80-1.22, P=0.88) respectively. Recurrence free and overall survival among metformin users and nonusers was also similar (HR 0.71, 95% CI 0.43-1.17, p=0.18) and (HR 0.81 (95% CI 0.60-1.08, p=0.14) respectively. Conclusions: In this large retrospective cohort of BTC patients, statin, aspirin or metformin use was not associated with improved recurrence free or overall survival.


Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1451
Author(s):  
Michele Da Broi ◽  
Paola Borrelli ◽  
Torstein R. Meling

Background: Although gross total resection (GTR) is the goal in meningioma surgery, this can sometimes be difficult to achieve in skull base meningiomas. We analyzed clinical outcomes and predictors of survival for subtotally resected benign meningiomas. Methods: A total of 212 consecutive patients who underwent subtotal resection (STR) for benign skull base meningioma between 1990–2010 were investigated. Results: Median age was 57.7 [IQR 18.8] years, median preoperative Karnofsky performance status (KPS) was 80.0 [IQR 20.0], 75 patients (35.4%) had posterior fossa meningioma. After a median follow-up of 6.2 [IQR 7.9] years, retreatment (either radiotherapy or repeated surgery) rate was 16% at 1-year, 27% at 3-years, 34% at 5-years, and 38% at 10-years. Ten patients (4.7%) died perioperatively, 9 (3.5%) had postoperative hematomas, and 2 (0.8%) had postoperative infections. Neurological outcome at final visit was improved/stable in 122 patients (70%). Multivariable analysis identified advanced age and preoperative KPS < 70 as negative predictors for overall survival (OS). Patients who underwent retreatment had no significant reduction of OS. Conclusions: Advanced age and preoperative KPS were independent predictors of OS. Retreatments did not prolong nor shorten the OS. Clinical outcomes in STR skull base meningiomas were generally worse compared to cohorts with high rates of GTR.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dominic O’Connor ◽  
Malcolm Brown ◽  
Martin Eatock ◽  
Richard C. Turkington ◽  
Gillian Prue

Abstract Background Surgical resection remains the only curative treatment for pancreatic cancer and is associated with significant post-operative morbidity and mortality. Patients eligible for surgery, increasingly receive neo-adjuvant therapy before surgery or adjuvant therapy afterward, inherently exposing them to toxicity. As such, optimizing physical function through exercise during treatment remains imperative to optimize quality of life either before surgery or during rehabilitation. However, current exercise efficacy and prescription in pancreatic cancer is unknown. Therefore, this study aims to summarise the published literature on exercise studies conducted in patients with pancreatic cancer undergoing treatment with a focus on determining the current prescription and progression patterns being used in this population. Methods A systematic review of four databases identified studies evaluating the effects of exercise on aerobic fitness, muscle strength, physical function, body composition, fatigue and quality of life in participants with pancreatic cancer undergoing treatment, published up to 24 July 2020. Two reviewers independently reviewed and appraised the methodological quality of each study. Results Twelve studies with a total of 300 participants were included. Heterogeneity of the literature prevented meta-analysis. Exercise was associated with improvements in outcomes; however, study quality was variable with the majority of studies receiving a weak rating. Conclusions High quality evidence regarding the efficacy and prescription of exercise in pancreatic cancer is lacking. Well-designed trials, which have received feedback and input from key stakeholders prior to implementation, are required to examine the impact of exercise in pancreatic cancer on key cancer related health outcomes.


Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1489
Author(s):  
John M. Rieth ◽  
Umang Swami ◽  
Sarah L. Mott ◽  
Mario Zanaty ◽  
Michael D. Henry ◽  
...  

Brain metastases commonly develop in melanoma and are associated with poor overall survival of about five to nine months. Fortunately, new therapies, including immune checkpoint inhibitors and BRAF/MEK inhibitors, have been developed. The aim of this study was to identify outcomes of different treatment strategies in patients with melanoma brain metastases in the era of checkpoint inhibitors. Patients with brain metastases secondary to melanoma were identified at a single institution. Univariate and multivariable analyses were performed to identify baseline and treatment factors, which correlated with progression-free and overall survival. A total of 209 patients with melanoma brain metastases were identified. The median overall survival of the cohort was 5.3 months. On multivariable analysis, the presence of non-cranial metastatic disease, poor performance status (ECOG 2–4), whole-brain radiation therapy, and older age at diagnosis of brain metastasis were associated with poorer overall survival. Craniotomy (HR 0.66, 95% CI 0.45–0.97) and treatment with a CTLA-4 checkpoint inhibitor (HR 0.55, 95% CI 0.32–0.94) were the only interventions associated with improved overall survival. Further studies with novel agents are needed to extend lifespan in patients with brain metastases in melanoma.


Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1612
Author(s):  
Julie Earl ◽  
Emma Barreto ◽  
María E. Castillo ◽  
Raquel Fuentes ◽  
Mercedes Rodríguez-Garrote ◽  
...  

Pancreatic ductal adenocarcinoma (PDAC) presents many challenges in the clinic and there are many areas for improvement in diagnostics and patient management. The five-year survival rate is around 7.2% as the majority of patients present with advanced disease at diagnosis that is treatment resistant. Approximately 10–15% of PDAC cases have a hereditary basis or Familial Pancreatic Cancer (FPC). Here we demonstrate the use of circulating free DNA (cfDNA) in plasma as a prognostic biomarker in PDAC. The levels of cfDNA correlated with disease status, disease stage, and overall survival. Furthermore, we show for the first time via BEAMing that the majority of hereditary or familial PDAC cases (around 84%) are negative for a KRAS somatic mutation. In addition, KRAS mutation negative cases harbor somatic mutations in potentially druggable genes such as KIT, PDGFR, MET, BRAF, and PIK3CA that could be exploited in the clinic. Finally, familial or hereditary cases have a longer overall survival compared to sporadic cases (10.2 vs. 21.7 months, respectively). Currently, all patients are treated the same in the clinic with cytotoxic agents, although here we demonstrate that there are different subtypes of tumors at the genetic level that could pave the way to personalized treatment.


2021 ◽  
Vol 22 (1) ◽  
pp. 118-121
Author(s):  
V. U. Rayn ◽  
◽  
M. A. Persidskiy ◽  
E. V. Malakhova ◽  
I. V. Anuchina ◽  
...  

Aim. To establish the association between pancreatic cancer precursor lesions and chronic opisthorchiasis. Materials and methods. A single center case-control study was conducted at a low-volume pancreatic surgery center in Khanty-Mansiysk. We retrospectively collected morphological data from 47 pancreatoduodenectomies performed for pancreatic ductal adenocarcinoma. The study group included 23 cases of pancreatic ductal adenocarcinoma with concomitant chronic Opisthorchis felineus invasion which were compared to 24 controls consisting of “pure” cancer. Qualitative analysis was performed using χ2 Pearson criterion. Exact Fisher test was used for small samples. Time to progression and overall survival rates were calculated using Kaplan-Meier survival analysis. Data were collected and analyzed in Statistica 7.0. Results. PanINs were seen in 41,7% pancreata resected for ductal adenocarcinoma of the head and in 95,7% cases of pancreatic cancer in background of chronic opisthorchiasis (р = 0,000; 95% CI 3,5-268). PanIN high grade were observed only in opisthorchiasis group. In mixed pathology invasive cancer component tended to be more dedifferentiated and advanced when compared to pure cancer group (p = 0,029). Median disease free survival was 9 mo. in both groups and overall survival was 13 mo. in non-opisthorchiasis group and 15,3 mo. in opisthorchiasis group (р = 0,437). Conclusion. Chronic opisthorchiasis is associated with pancreatic intraepithelial neoplasia. Pancreatic ductal adenocarcinoma in background of opisthorchiasis with preneoplastic lesions tend to be more advanced in stage and poorly differentiated. Disease free and overall survival have no statistically significant differences in patients with and without Opisthorchis felineus invasion.


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