The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference was held in Halifax, Nova Scotia, 20–22 September 2018. Experts in radiation oncology, medical oncology, surgical oncology, and pathology who are involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics in the management of pancreatic cancer, pancreatic neuroendocrine tumours, hepatocellular cancer, and rectal and colon cancer, including■ surgical management of pancreatic adenocarcinoma,■ adjuvant and metastatic systemic therapy options in pancreatic adenocarcinoma,■ the role of radiotherapy in the management of pancreatic adenocarcinoma,■ systemic therapy in pancreatic neuroendocrine tumours,■ updates in systemic therapy for patients with advanced hepatocellular carcinoma,■ optimum duration of adjuvant systemic therapy for colorectal cancer, and■ sequence of therapy in oligometastatic colorectal cancer.
(1) Background: The management of gastrointestinal stromal tumors (GIST) has significantly evolved over the last two decades, with the introduction of tyrosine kinase inhibitors (TKI). We aim to report 10 years of experience of GIST management at a regional cancer center in Canada. (2) Methods: We retrospectively analyzed the records of 248 consecutive patients diagnosed with GIST between 2011 and 2021. We describe the clinical and pathological data, management, and outcome, including survival. (3) Results: The most common GIST sites were the stomach 63% (156), followed by the small bowel 29% (73). At diagnosis, 83% (206) of patients had localized disease (stage I–III). According to the modified National Institutes of Health consensus criteria (NIH) for GIST, around 45% (90) had intermediate or high-risk disease. Most patients, 86% (213), underwent curative surgical resection. Forty-nine patients received adjuvant imatinib, while forty-three patients had advanced disease and received at least one line of TKI. With a median follow-up of 47 months, the 5-year recurrence-free survival (RFS) rates for very low and low risk were 100% and 94%, respectively, while those for intermediate and high risk were 84% and 51%, respectively. The 5-year overall survival (OS) rates for very low and low risk were 100% and 94%, while intermediate, high risk, and advanced were 91%, 88%, and 65%, respectively. Using the Kaplan–Meier method, there were statistically significant differences in RFS and OS between NIH risk groups, p < 0.0005. In univariate analysis, ECOG, site, mitosis, secondary malignancy, and size were predictors for OS. High mitosis and large size (>5 cm) were associated with worse RFS. (4) Conclusions: Curative surgical resection remains the gold standard management of GIST. Our results are comparable to the reported literature. Further research is needed to explore histology’s role in risk stratification and initiating adjuvant TKI.
(1) Aim: The prevalence and incidence of small bowel NETs have increased significantly over the past two decades. This study aims to report the 10-year experience of SB-NET management at a regional cancer center in Canada. (2) Materials and methods: We conducted a retrospective study of the clinical and pathological data of patients diagnosed with biopsy-proven SB-NET at The Ottawa Hospital (TOH), Ottawa, Canada between 2011 and 2021. We report the clinicopathological characteristics of these patients, as well as their outcomes data, including survival rates. (3) Results: Between 2011 and 2021, a total of 177 SB-NET cases were identified with 51% (n = 91) of cases being males. The most common sites of the tumors were the ileum 53% (n = 94), followed by the duodenum 9% (n = 16) and jejunum 7% (n = 12). Approximately 24% (n = 42) of the patients had symptoms for over six months prior to diagnosis and 18% (n = 32) had functioning SB-NET during the course of the disease. The majority of patients had locally advanced or metastatic disease at the time of presentation with stage III, and stage IV representing 42% (n = 75), and 41% (n = 73) respectively. The majority of patients 84% (n = 148) had well-differentiated histology. One hundred twenty patients underwent surgical resection of the primary tumor including 28 patients (16%) with limited metastatic disease. A total of 21 patients (18%) had recurrence after curative surgery. A total of 62 patients (35%) received first-line somatostatin analog (SSA) therapy for unresectable disease and seven patients had PRRT after progression on SSA. Five years OS was 100%, 91%, 97%, and 73% for stages I, II, III, and IV respectively. In univariate analysis, carcinoid symptoms, T stage, and differentiation were significant predictors for worse overall survival, but not RFS. (4) Conclusions: Compared to published historical controls, our study suggests improvement in the 5-year survival rate of SB-NETs over the last 10 years.
11536 Background: The secondary malignancies in patients with GIST are relatively high. We present our 10-year experience of SPM in patients with GIST from a regional Cancer Centre in Canada. Methods: A retrospective cohort study was performed in all GIST patients treated at TOH between January 2011 and December 2021. Patients were identified using ICD-10 codes and electronic medical records reviewed. Clinicopathological data were analyzed. Logistic regression analysis was used to evaluate associated factors with SPM. Survival analysis was estimated with the use of the Kaplan-Meir method and compared by log-rank test. Results: In total, 248 patients with GIST were identified. Of these patients, 61 (25%) had SPM; synchronous (9, 15%) and metachronous (52, 85%). Nine patients had two additional primary cancers other than GIST, and four patients had three additional primary cancers. The median age at diagnosis was 70 (range 44 – 90) years, and males were (59%). The most common SPMs were skin cancer (14, 17%), melanoma (5), and non-melanoma (9), followed by prostate cancer (13, 16%) and breast cancer (12, 15%). Colorectal cancer and hematological malignancies were found in (5, 11%) patients each, while RCC was found in (4, 6%). Thyroid cancer, lung cancer, neuroendocrine tumor, bladder cancer, thymoma, and other types of cancers were collectively found in 15 patients (24%). The majority (57%) of SPM diagnosed before GIST, 30% after GIST. The most common primary GIST locations were in the stomach (62%), followed by the small bowel (30%), and the most common histology was spindle cell (69%), followed by mixed histology (13%). The majority of GIST were localized (46 patients, 75%). Based on Miettinen risk classes for non-metastatic GIST, 74% had zero to low-risk disease, while 26% had moderate or high-risk disease. There was no association between SPM and GIST primary site (p = 0.4), TNM stage (p = 0.8), histology (p = 0.2), Mitosis (p = 0.5), and Miettinen risk class (p = 0.6). The median follow-up time was 53 months (range 1 – 132), and four patients lost follow-ups. Five years overall survival of SPM group vs. non SPM, 79.8% vs. 94.1%, (p = 0.03). Cox regression did not reveal a significant association with the covariants Conclusions: We observed that one out of four GIST patients have SPM. Skin, prostate, breast cancers were the most common SPM associated with GIST. Molecular studies are needed to explore the association/underlying mechanisms of GIST with these malignancies.
Background: PD-1/PDL-1 inhibitors are active in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) and improve progression-free survival (PFS) and overall survival (OS) when added to chemotherapy, even in tumors with low PDL-1 expression. We recently reported that for most agents assessed in most solid tumors, PFS and OS curves follow first order kinetics (Stewart Crit Rev Oncol Hematol 2020 Apr;148:102896; Stewart Crit Rev Oncol Hematol 2020 Sep;153103039). On log-linear plots, some curves approximate straight lines. Some have late convexity, potentially due to therapy interruption or dose reduction. Some have an inflection point to the right and fit 2 phase models on exponential decay nonlinear regression analysis (EDNLRA), potentially due to presence of 2 distinct subpopulations with differing rates of progression or death. Most PD-1/PDL-1 curves have 2 phase decay (suggesting distinct sensitive and resistant populations defined by a dichotomous present-vs-absent factor), while the majority of log-linear plots for chemotherapy are convex or approximate straight lines. Here we assessed characteristics of PFS and OS curves for PD-1/PDL-1 inhibitors when combined with chemotherapy. Methods: Published NSCLC and SCLC PFS and OS curves were digitized using the application https://apps.automeris.io/wpd/. GraphPad Prism 7 was used for 1 phase and 2 phase decay EDNLRA. Terminal curve portions with fewer than 10 remaining patients were excluded. Results: For chemotherapy, 22 of 152 PFS curves (14%) and 8 of 102 OS curves (8%) fit 2-phase decay models per our published definition, compared to 43 of 47 PFS curves (91%) and 24 of 24 OS curves (100%) for PD-1/PDL-1 inhibitors, and 1 of 18 PFS curves (6%) and 5 of 18 OS curves (28%) for PD-1/PDL1 inhibitors combined with chemotherapy (p less than 0.0001). Results were similar for SCLC (20 PFS and 27 OS curves) and NSCLC (197 PFS curves and 117 OS curves assessed). Conclusions: PFS and OS population kinetic characteristics for combinations of PD-1/PDL-1 inhibitors with chemotherapy are much more similar to those seen with chemotherapy than for those with single agent PD-1/PDL-1 inhibitors. The underlying biological reasons are uncertain, but this observation suggests that PD-1/PDL-1 inhibitors may potentiate chemotherapy in some tumors that are not intrinsically sensitive to these inhibitors as single agents. Alternatively, concurrent chemotherapy might antagonize the unknown mechanism of resistance to immunotherapy that drives 2 phase PFS and OS curve decay. This raises the question whether PD-1/PDL-1 inhibitors and chemotherapy might also potentiate each other in other tumor types not generally regarded as being sensitive to PD-1/PDL-1 inhibitors (eg, resistant breast and colon cancer variants, EGFR mutant NSCLC, etc). Citation Format: David J. Stewart, Abdulaziz Alshareef Aljassim. Potential implications of population kinetic characteristics of PD-1/PDL-1 monoclonals combined with chemotherapy in lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 441.
e19268 Background: Prior studies have demonstrated that clonal cells that give rise to pancreatic peritoneal metastases (PM) are geographically and genetically distinct from clonal cells, giving rise to lung and liver metastases. The objective of this study was to assess if there is a distinct difference in prognosis and therapeutic response among patients with pancreatic cancer with (PM compared to the lung/liver. Methods: Using a retrospective cohort design, medical records from adult patients diagnosed with metastatic adenocarcinoma of the pancreas at five Canadian academic cancer centers (2014 - 2019) were reviewed. Prognostic variables including age, Charlson comorbidity index, ECOG, cigarette smoking, nodal status, sites of metastases, and first line chemotherapy were collected. Cox proportional hazards model (MVA) was used to examine the association between peritoneal involvement and survival, adjusted for measured confounders. Analyses were completed using SAS, where alpha of 0.05 was defined as the level of significance. Results: A total of 1161 patients were included. Metastatic sites included peritoneum (n = 170, 14.6%), lung (n = 145, 12.5%) and liver (n = 563, 48.5%). Patients with PM received first-line FOLFIRINOX (FFX, n = 31), Gemcitabine + nab-paclitaxel (G/N, n = 20), Gemcitabine (G, n = 18), and no treatment (n = 97). In univariate analyses, worse ECOG PS was associated with PM (p = 0.002). The majority of patients died (89%), with a median overall survival (OS) of 3 vs 7 months for patients with PM and those without PM (p < 0.001), respectively. The median OS in patient whom receive first-line chemotherapy was 7 months in FFX group (95% CI 1.66-12.33), 6 months in G/N (95% CI 4.54-7.45) and 2 months in G group (95% CI 1.42-2.57). Patients had significantly better OS when treated with FFX or G/N compared to G alone (p = 0.002). Time to treatment failure was significantly shorter among patient treated with G alone compare to patients treated with FFX and G/N (P < 0.005). Conclusions: In the setting of combination chemotherapy for advanced pancreatic cancer, patients with PM continue to have a poor prognosis. This may be due to the impact of PM on PS and the inability to administer palliative chemotherapy. For eligible patients, FFX or G/N results in a higher OS than G monotherapy.
e19267 Background: Pancreatic cancer is the fourth leading cause of cancer-related death with an average life expectancy of approximately six months following diagnosis. It is essential to understand the behavior of cancer cells to predict pattern of progression. Previous studies have shown that location of pancreatic adenocarcinoma has an influence on overall survival (OS) with worse OS among patient whom developed pancreatic cancer in the tail of pancreas. The objective of this study was to determine if location of the primary pancreatic adenocarcinoma (head/neck vs. body vs. tail) has an influence on overall survival and study pattern of metastasis to lung, liver and peritoneum base on primary tumor site. Methods: A retrospective cohort design was used to identify cases of advanced adenocarcinoma pancreas and to assess disease and treatment-related characteristics. Medical records from all adult patients diagnosed with metastatic pancreatic cancer across five Canadian academic cancer centers in Canada from 2014 to 2019 were reviewed using a national Research Electronic Data Capture (REDCap) database. Prognostic variables including age, Charlson comorbidity index, ECOG, cigarette smoking, nodal status, sites of metastases, and type of first line chemotherapy were collected. Cox proportional hazards model was used to examine the association between anatomical location of pancreatic cancer and survival, adjusted for measured confounders. Analyses were completed using SAS, where alpha of 0.05 was defined as the level of significance. Results: A total of 1161 participants were included in the study. The primary origin of pancreatic cancer included head/neck (51.8%), tail (20%) and body (16%). Metastatic sites included peritoneum (n = 170), lung (n = 145), and liver (n = 563). Peritoneal metastasis originated from tail (21.3%) and body (16.8%) and less from head /neck (9.1%) (P < 0.001). Liver metastasis originated from body (52.7%) and tail (66%) and less from head/neck (37%) (P < 0.001). Lung metastasis originated from body (13.6%) and tail (19.6%) and less from head/neck (7.8%) (p < 0.001). Multivariate analyses (MVA) showed that primary tumour location was not associated with overall survival (p > 0.05). Conclusions: Pancreatic lesions that originate in the body and tail were more likely to metastasize to lung, liver and peritoneum. Anatomical location of the primary pancreatic cancer was not associated with overall survival.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.