scholarly journals High practice variation in risk stratification, baseline oncological staging, and follow-up strategies for T1 colorectal cancers in the Netherlands

2020 ◽  
Vol 08 (09) ◽  
pp. E1117-E1122 ◽  
Author(s):  
Kim Gijsbers ◽  
Wilmar de Graaf ◽  
Leon M.G. Moons ◽  
F. ter Borg ◽  

Abstract Background and study aims Based on pathology, locally resected T1 colorectal cancer (T1-CRC) can be classified as having low- or high-risk for irradicality and/or lymph node metastasis, the latter requiring adjuvant surgery. Reporting and application of pathological high-risk criteria is likely variable, with inherited variation regarding baseline oncological staging, treatment and surveillance. Methods We assessed practice variation using an online survey among gastroenterologists and surgeons participating in the Dutch T1-CRC Working Group. Results Of the 130 invited physicians, 53 % participated. Regarding high-risk T1-CRC criteria, lymphangio-invasion is used by 100 %, positive or indeterminable margins by 93 %, poor differentiation by 90 %, tumor-free margin ≤ 1 mm by 78 %, tumor budding by 57 % and submucosal invasion > 1000 µm by 47 %. Fifty-two percent of the respondents do not perform baseline staging in locally resected low-risk T1-CRC. In case of unoperated high-risk patients, we recorded 61 different surveillance strategies in 63 participants, using 19 different combinations of diagnostic tests. Endoscopy is used in all schedules. Mean follow-up time is 36 months for endoscopy, 26 months for rectal MRI and 30 months for abdominal CT (all varying 3–60 months). Conclusion We found variable use of pathological high-risk T1-CRC criteria, creating risk for misclassification as low-risk T1-CRC. This has serious implications, as most participants will not proceed to oncological staging in low-risk patients and adjuvant surgery nor radiological surveillance is considered. On the other hand, oncological surveillance in patients with a locally resected high-risk T1-CRC who do not wish adjuvant surgery is highly variable emphasizing the need for a uniform surveillance protocol.

2021 ◽  
Vol 24 (3) ◽  
pp. 680-690
Author(s):  
Michiel C. Mommersteeg ◽  
Stella A. V. Nieuwenburg ◽  
Wouter J. den Hollander ◽  
Lisanne Holster ◽  
Caroline M. den Hoed ◽  
...  

Abstract Introduction Guidelines recommend endoscopy with biopsies to stratify patients with gastric premalignant lesions (GPL) to high and low progression risk. High-risk patients are recommended to undergo surveillance. We aimed to assess the accuracy of guideline recommendations to identify low-risk patients, who can safely be discharged from surveillance. Methods This study includes patients with GPL. Patients underwent at least two endoscopies with an interval of 1–6 years. Patients were defined ‘low risk’ if they fulfilled requirements for discharge, and ‘high risk’ if they fulfilled requirements for surveillance, according to European guidelines (MAPS-2012, updated MAPS-2019, BSG). Patients defined ‘low risk’ with progression of disease during follow-up (FU) were considered ‘misclassified’ as low risk. Results 334 patients (median age 60 years IQR11; 48.7% male) were included and followed for a median of 48 months. At baseline, 181/334 (54%) patients were defined low risk. Of these, 32.6% were ‘misclassified’, showing progression of disease during FU. If MAPS-2019 were followed, 169/334 (51%) patients were defined low risk, of which 32.5% were ‘misclassified’. If BSG were followed, 174/334 (51%) patients were defined low risk, of which 32.2% were ‘misclassified’. Seven patients developed gastric cancer (GC) or dysplasia, four patients were ‘misclassified’ based on MAPS-2012 and three on MAPS-2019 and BSG. By performing one additional endoscopy 72.9% (95% CI 62.4–83.3) of high-risk patients and all patients who developed GC or dysplasia were identified. Conclusion One-third of patients that would have been discharged from GC surveillance, appeared to be ‘misclassified’ as low risk. One additional endoscopy will reduce this risk by 70%.


2020 ◽  
Vol 41 (Supplement_1) ◽  
Author(s):  
W Sun ◽  
B P Y Yan

Abstract Background We have previously demonstrated unselected screening for atrial fibrillation (AF) in patients ≥65 years old in an out-patient setting yielded 1-2% new AF each time screen-negative patients underwent repeated screening at 12 to 18 month interval. Selection criteria to identify high-risk patients for repeated AF screening may be more efficient than repeat screening on all patients. Aims This study aimed to validate CHA2DS2VASC score as a predictive model to select target population for repeat AF screening. Methods 17,745 consecutive patients underwent 24,363 index AF screening (26.9% patients underwent repeated screening) using a handheld single-lead ECG (AliveCor) from Dec 2014 to Dec 2017 (NCT02409654). Adverse clinical outcomes to be predicted included (i) new AF detection by repeated screening; (ii) new AF clinically diagnosed during follow-up and (ii) ischemic stroke/transient ischemic attack (TIA) during follow-up. Performance evaluation and validation of CHA2DS2VASC score as a prediction model was based on 15,732 subjects, 35,643 person-years of follow-up and 765 outcomes. Internal validation was conducted by method of k-fold cross-validation (k = n = 15,732, i.e., Leave-One-Out cross-validation). Performance measures included c-index for discriminatory ability and decision curve analysis for clinical utility. Risk groups were defined as ≤1, 2-3, or ≥4 for CHA2DS2VASC scores. Calibration was assessed by comparing proportions of actual observed events. Results CHA2DS2VASC scores achieved acceptable discrimination with c-index of 0.762 (95%CI: 0.746-0.777) for derivation and 0.703 for cross-validation. Decision curve analysis showed the use of CHA2DS2VASC to select patients for rescreening was superior to rescreening all or no patients in terms of net benefit across all reasonable threshold probability (Figure 1, left). Predicted and observed probabilities of adverse clinical outcomes progressively increased with increasing CHA2DS2VASC score (Figure 1, right): 0.7% outcome events in low-risk group (CHA2DS2VASC ≤1, predicted prob. ≤0.86%), 3.5% intermediate-risk group (CHA2DS2VASC 2-3, predicted prob. 2.62%-4.43%) and 11.3% in high-risk group (CHA2DS2VASC ≥4, predicted prob. ≥8.50%). The odds ratio for outcome events were 4.88 (95%CI: 3.43-6.96) for intermediate-versus-low risk group, and 17.37 (95%CI: 12.36-24.42) for high-versus-low risk group.  Conclusion Repeat AF screening on high-risk population may be more efficient than rescreening all screen-negative individuals. CHA2DS2VASC scores may be used as a selection tool to identify high-risk patients to undergo repeat AF screening. Abstract P9 Figure 1


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8030-8030 ◽  
Author(s):  
Ralf Ulrich Trappe ◽  
Daan Dierickx ◽  
Petra Reinke ◽  
Ruth Neuhaus ◽  
Franck Morschhauser ◽  
...  

8030 Background: The prospective, multicenter international phase II PTLD-1 trial of sequential treatment (ST, 4 cycles of weekly rituximab followed by 4 cycles of CHOP-21 + G-CSF) in adult CD20-positive PTLD demonstrated excellent efficacy (90% overall response rate, ORR) and safety (11% treatment-related mortality, TRM). As the response to rituximab predicted overall survival (OS), the trial was amended in 2007 introducing risk-stratified sequential treatment (RSST) according to the response to rituximab (NCT00590447). Methods: Following rituximab on days 1, 8, 15 and 22, RSST consisted of 4 3-weekly courses of rituximab monotherapy for patients (pts) in complete remission (CR, low risk) while all others (high risk) received 4 cycles of R-CHOP-21 + G-CSF. Key exclusion criteria were CNS involvement, HIV infection, severe organ dysfunction not related to PTLD, and ECOG > 2. Primary endpoint was ORR. This is an analysis of the first 91 patients treated with RSST. Results: 79/91 pts had monomorphic, 12 polymorphic PTLD. 41/91 pts were kidney, 27 liver, 12 heart, 7 lung or heart+lung, 3 heart+kidney and 1 kidney+pancreas transplant recipients. Median age at diagnosis was 60 years (range 20-82). 73/91 pts had late PTLD and 39/85 PTLDs were EBV-associated. 1 pt died before initiation of treatment; 5 pts discontinued treatment after 4 cycles rituximab. TRM of RSST was 7/90 (8%) including 5 deaths with unknown remission status. ORR was thus 74/80 (93%, 95%CI: 84-97%; CR: 62/80 [78%]). 24/90 pts (27%) achieved CR with 4 cycles of rituximab. After a median follow up of >3 years, relapse rate in low risk pts was not increased by rituximab consolidation in RSST compared to CHOP consolidation in ST (3/23 vs. 5/14, p=0.104]). In patients in PD after rituximab, R-CHOP was more effective than CHOP in achieving CR (15/23 vs. 3/11, p=0.038). OS at 3 years was higher with RSST (70%, 95% CI: 60-82%) compared to ST (61%, 95%CI 49-72%) but this difference was not significant. Conclusions: With RSST 27% of pts were classified as low risk and achieved durable tumor control without chemotherapy while R-CHOP seems more efficient than CHOP in in high risk patients.


2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 378-378 ◽  
Author(s):  
Scott Kopetz ◽  
Zhi-Qin Jiang ◽  
Michael J. Overman ◽  
Christa Dreezen ◽  
Sun Tian ◽  
...  

378 Background: Although the benefit of chemotherapy in stage II and III colon cancer patients is significant, many patients might not need adjuvant chemotherapy because they have a good prognosis even without additional treatment. ColoPrint is a gene expression classifier that distinguish patients with low or high risk of disease relapse. It was developed using whole genome expression data and has been validated in public datasets, independent European patient cohorts and technical studies (Salazar 2011 JCO, Maak 2012 Ann Surg). Methods: In this study, the commercial ColoPrint test was validated in stage II (n=96) and III patients (n=95) treated at the MD Anderson Cancer Center from 2003 to 2009. Frozen tissue specimen, clinical parameters, MSI-status and follow-up data (median follow-up 64 months) were available. The 64-gene MSI-signature developed to identify patients with deficient mismatch repair system (Tian 2012 J Path) was evaluated for its accuracy to identify MSI patients and also for prognosis. Results: In this cohort, ColoPrint classified 56% of stage II and III patients as being at low risk. The 3-year Relapse-Free-Survival (RFS) was 90.6% for Low Risk and 78.4% for High Risk patients with a HR of 2.33 (p=0.025). In uni-and multivariate analysis ColoPrint and stage were the only significant factors to predict outcome. The MSI-signature classified 47 patients (24.6%) as MSI-H and most MSI-H patients were ColoPrint low risk (81%). Patients who were ColoPrint low risk and MSI-H by signature had the best outcome with a 3-year RFS of 95% while patients with ColoPrint high risk had a worse outcome independently of the MSI-status. Low risk ColoPrint patients had a good outcome independent of stage or chemotherapy treatment (90.1% 3-year RFS for treated patients, 91.4% for untreated patients) while ColoPrint high risk patients treated with adjuvant chemotherapy had 3-year RFS of 84%, compared to 70.1% 3-year RFS in untreated patients (p=0.026). Conclusions: The combination of ColoPrint and MSI-Print improves the prognostic accuracy in stage II and stage III patients and may help the identification of patients at higher risk who are more likely to benefit from additional treatment


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2018-2018
Author(s):  
E. Franceschi ◽  
A. Tosoni ◽  
M. Ermani ◽  
V. Blatt ◽  
P. Amistà ◽  
...  

2018 Background: Due to the rarity of medulloblastoma (MB) in adults, the few studies available on this condition are retrospective, and the follow-up tends to be short. Furthermore, the different therapeutic strategies used in these patients makes it difficult to assess survival rates and prognostic factors. Methods: Between January 1989 and February 2001, a prospective phase II trial was performed to evaluate the efficacy of treatment for adults with medulloblastoma. Patients were completely staged with a neuroradiological examination of the brain and neuraxis and by CSF cytology, according to Chang’s staging system. Low risk patients received radiotherapy alone, while high risk patients were given 2 cycles of upfront chemotherapy followed by radiotherapy and adjuvant chemotherapy. The results of the preliminary analysis of this study at a median follow-up of 3.7 years are reported elsewhere. The present papers reports on the long- term results of the same trial. Results: After a median follow up of 7.6 years, among a total of 36 enrolled adults with medulloblastoma, overall progression free survival (PFS) and overall survival (OS) at 5 years were 72% (range 59% to 84%) and 75% (62% to 91%), respectively. No difference was found between low and high risk patients in terms of PFS and OS at 5 years: in low-risk patients the 5-year PFS was 80% (range, 59–100%) and the 5-year OS, 80% (range, 58 - 100%); in high-risk patients the 5-year PFS was 69% (range, 54 -89%) and the 5-year OS, 73% (range, 58 - 92%). Conclusions: A long-term follow-up is essential to evaluate the real impact of treatments in adult patients with MB. Since there is no significant difference between low-risk and high-risk patients for PFS and OS, the use of chemotherapy is also questionable in low-risk patients. No significant financial relationships to disclose.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 1-2
Author(s):  
Srdan Verstovsek ◽  
Ariel Han ◽  
Karin Chun Hayes ◽  
Tracy Woody ◽  
Frank Valone ◽  
...  

BACKGROUND Polycythemia Vera (PV) is a rare myeloproliferative neoplasm associated with an increased production of red blood cells, white blood cells, and platelets. Most frequent treatment includes phlebotomy, hydroxyurea, interferon, and ruxolitinib. Current NCCN guideline recommends managing HCT levels to below 45%. The objective of this study was to determine real-world standards of care and patient characteristics, and to observe how treatment decisions vary by HCT level and thrombosis risk. METHODOLOGY We conducted a retrospective study using Symphony Health's longitudinal transactional healthcare claims database that includes prescription, medical and hospital claims across > 4,900 US payers representing 86% of US lives. Eligible patients had at least one ICD-10 diagnosis code for PV and at least one of the treatments including phlebotomy, hydroxyurea, busulfan, interferon, and ruxolitinib between Jan 1, 2018 and Dec 31, 2019 (index period). For eligible patients, all prior treatment history initiated as far back as January 2010 was used to report therapy changes. Patients were also required to have at least one PV diagnosis within a year of treatment initiation and at least 2 HCT lab results during the index period. PV treatment changes and characteristics were studied. RESULTS Out of 28,306 patients with PV, 4,264 patients had HCT lab data for 2 years (index period). Median duration of follow-up was 854 days (range 98-3,373days). Patient therapy duration was from 1 to 9 years. Median patient age was 65 (range 11-94), with 1,451 (34%) patients aged less than 60, 2,813 (66%) 60 years or older, and a substantial male predominance (62% vs 38%). 1,247 (29%) patients were classified as Low Risk (age< 60 with no TE history) and 3,017 (71%) patients as High Risk. Within the High-Risk group, 2,224 (52%) were age>60 without prior TE, 204 (5%) were age<60 with prior TE and 589 (14%) were age>60 with prior TE. For Low Risk patients' initial treatment was phlebotomy alone (85%) and a total of 73% of all Low Risk patients remained on phlebotomy alone. For High Risk patients' initial treatment was phlebotomy alone (60%) and 43% all of High-Risk patients remained on phlebotomy alone (Figure 1). The median HCT prior to treatment initiation was 52.9% and 48% during treatment. 936 (22%) patients achieved NCCN treatment guidelines with HCT levels always remaining under 45%, and 1,226 (29%) patients had HCT levels controlled between 45% and 50%. However, 2,102 (49%) patients had some or all HCT levels> 50% (Figure 2). With the most recent lab test, 2,180 (51%) of patients still had HCTs above 45% and 804 (19%) were still above 50%. In a sub-cohort of 653 High Risk patients with a prior TE and up to 5 years of follow up, 236 (36%) had at least one other TE; for the 1,774 High Risk patients who did not have the history of thrombosis, 161(9%) had at least one TE (Table 2). The most common TE since treatment began in patients with prior TE were deep vein thrombosis (n= 92 patients, 14%) and stroke (n= 95 patients, 15%). Among High Risk patients (n=397) who had another thrombotic event, 180 (45%) were treated by phlebotomy only and never switched to any other therapies. CONCLUSIONS Despite currently available treatments in US, patients' HCT level after treatment were higher than recommended as per guidelines. Failure to maintain HCT less than 45% increases the risk of future thrombotic events as shown by 36% of patients with prior TE experiencing another TE within the next 5 years. Disclosures Verstovsek: Sierra Oncology: Consultancy, Research Funding; ItalPharma: Research Funding; Blueprint Medicines Corp: Research Funding; NS Pharma: Research Funding; Promedior: Research Funding; Incyte Corporation: Consultancy, Research Funding; Protagonist Therapeutics: Research Funding; Novartis: Consultancy, Research Funding; Roche: Research Funding; AstraZeneca: Research Funding; PharmaEssentia: Research Funding; Genentech: Research Funding; Celgene: Consultancy, Research Funding; Gilead: Research Funding; CTI Biopharma Corp: Research Funding. Han:Protagonist Therapeutics: Consultancy. Chun Hayes:Protagonist: Consultancy. Woody:Protagonist: Current Employment. Valone:Protagonist: Current Employment. Gupta:Protagonist: Current Employment.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1015-1015 ◽  
Author(s):  
Ash A Alizadeh ◽  
James S. McClellan ◽  
Jason R. Gotlib ◽  
Steven Coutre ◽  
Ravindra Majeti ◽  
...  

Abstract Abstract 1015 Poster Board I-37 Background: Early mortality, mostly from hemorrhagic complications, occurs in less than 10% of patients currently treated in clinical trials for acute promyelocytic leukemia (APL). However, data about the proportion of patients developing such complications prior to clinical trial enrollment are scarce in the literature (Sanz M, et al Blood 2009). Approximately 5% of newly diagnosed patients with APL have been reported not to be eligible for participation in clinical trials due to very poor clinical condition, and their outcome has never been reported. However, enrollment on clinical trials may be difficult in specific clinical situations, such as after hours/weekend admissions and/or emergent requirement for therapy. This study reports the incidence, time of occurrence and clinical features of APL patients with a focus on early mortality. Methods: 150 consecutive APL patients treated at Stanford University between 8/1986 and 7/2009 were identified. Thirteen patients were excluded for lack of appropriate clinical information. Clinical features of patients with APL were analyzed for factors that might be relate to prognosis, including age, gender, white blood cell count, platelet count, fibrinogen, PTT, and INR. Continuous variables were compared with the t-test and categorical variables by Fisher's exact test or X-square statistic. The Kaplan–Meier method was applied to assess overall survival time. Results: Of the 137 patients included in this analysis, the median age at diagnosis was 45 (1-93) years and 78 (57%) were females. Using the PETHEMA criteria, there were 37, 46 and 20 patients with high-, intermediate- and low-risk disease (34 patients could not be classified based on partial/missing data). With a median follow-up time of 748 (0-6,235) days for the entire cohort, 52 (38%) have died. 19 (14%) and 11 (8%) of these patients died within 7 and 3 days of presentation, respectively. Patients with high-risk features had a 13% and 24% chance of dying with 3 and 7 days of presentation, respectively, with significantly inferior outcomes (p=0.045) when compared to those with intermediate-risk patients (6% and 13%) and low-risk disease (5% and 5%). Patients with unknown risk category faired similarly to low-risk patients. The most common cause of early mortality in these 19 patients was intracranial hemorrhage (n=11). Patients with early death (ED) (either <=3 or <=7 days) tended to be older than APL patients with non-early deaths (>7d), or APL patients alive as of their last follow-up (median age 54 years vs. 50 years vs. 39 years), and were more likely to have higher risk disease, though coagulopathy appeared not significantly different amongst the groups. Median fibrinogen, PTT and INR for each individual group are presented on Table 1. The 3-year overall survival (% +/- SE) of the low, intermediate, and high risk patients was 90+/-7, 74+/-7, and 64+/-8, respectively, though early mortality (death within 7 days) was a major determinant of this stratification (p=0.045). Conclusions: Risk of early death in APL patients appears to be higher than previously reported in clinical trials, where trial registration may exclude patients requiring urgent therapeutic interventions. In this cohort, 25% and 13% patients with high- and intermediate-risk APL died within 7 days of presentation, respectively. Risk group stratification was very predictive of risk of early death. Disclosures: No relevant conflicts of interest to declare.


2011 ◽  
Vol 165 (3) ◽  
pp. 441-446 ◽  
Author(s):  
Maria Grazia Castagna ◽  
Fabio Maino ◽  
Claudia Cipri ◽  
Valentina Belardini ◽  
Alexandra Theodoropoulou ◽  
...  

IntroductionAfter initial treatment, differentiated thyroid cancer (DTC) patients are stratified as low and high risk based on clinical/pathological features. Recently, a risk stratification based on additional clinical data accumulated during follow-up has been proposed.ObjectiveTo evaluate the predictive value of delayed risk stratification (DRS) obtained at the time of the first diagnostic control (8–12 months after initial treatment).MethodsWe reviewed 512 patients with DTC whose risk assessment was initially defined according to the American (ATA) and European Thyroid Association (ETA) guidelines. At the time of the first control, 8–12 months after initial treatment, patients were re-stratified according to their clinical status: DRS.ResultsUsing DRS, about 50% of ATA/ETA intermediate/high-risk patients moved to DRS low-risk category, while about 10% of ATA/ETA low-risk patients moved to DRS high-risk category. The ability of the DRS to predict the final outcome was superior to that of ATA and ETA. Positive and negative predictive values for both ATA (39.2 and 90.6% respectively) and ETA (38.4 and 91.3% respectively) were significantly lower than that observed with the DRS (72.8 and 96.3% respectively,P<0.05). The observed variance in predicting final outcome was 25.4% for ATA, 19.1% for ETA, and 62.1% for DRS.ConclusionsDelaying the risk stratification of DTC patients at a time when the response to surgery and radioiodine ablation is evident allows to better define individual risk and to better modulate the subsequent follow-up.


Author(s):  
Sophie Leboulleux ◽  
Martin Jean Schlumberger

Papillary and follicular thyroid carcinomas are the most frequent forms of thyroid cancers and are among the most curable cancers. However, some patients are at high risk of recurrence or even death from their cancer, and can be identified at the time of diagnosis using well-established prognostic indicators (1–3). The apparent increase in the incidence of thyroid carcinomas observed in recent years is mainly related to an increased detection of low risk small carcinomas in adults, which is attributed to an improvement in diagnostic techniques (4, 5). This leads to the treatment of an increasing number of low-risk patients for whom an optimal quality of life should be maintained. However, the number of high-risk patients remains unchanged and these patients require aggressive treatment and follow-up. The extent of initial treatment and follow-up should therefore be individualized according to recent guidelines and consensus (6, 7).


Blood ◽  
2006 ◽  
Vol 107 (9) ◽  
pp. 3469-3473 ◽  
Author(s):  
Elihu Estey ◽  
Guillermo Garcia-Manero ◽  
Alessandra Ferrajoli ◽  
Stefan Faderl ◽  
Srdan Verstovsek ◽  
...  

We examined whether combining all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) might be an alternative to ATRA plus chemotherapy in untreated acute promyelocytic leukemia (APL). Twenty-five low-risk patients (white blood cell [WBC] count less than 10 × 109/L [10 000/μL]) received ATRA (45 mg/m2 daily) and ATO (0.15 mg/kg daily, beginning day 10 of ATRA), and in complete remission (CR) received ATO plus ATRA, without chemotherapy, unless they were reverse transcriptase–polymerase chain reaction (RT-PCR)–positive 3 months from CR date or had molecular relapse. Nineteen high-risk patients were treated identically, but received chemotherapy, generally 9 mg/m2 gemtuzumab ozogamycin (GO) on day 1 of induction. The CR rate was 39 of 44 (24 of 25 in low-risk, 15 of 19 in high-risk). Disease recurred at 9, 9, and 15 months, respectively, in 3 high-risk patients. The median follow-up time from CR date in the 36 patients alive in first CR is 16 months (15 months in low-risk, 20 months in high-risk), with 9 patients followed for at least 24 months. Each of the 36 patients was PCR-negative at last follow-up. Thus, none of the low-risk patients has received chemotherapy, and only 3 high-risk patients (the 3 with relapsed disease) have received chemotherapy past induction. ATRA plus ATO may serve as an alternative to chemotherapy in low-risk untreated APL (eg, in older patients) and, when combined with GO, may improve outcome in high-risk patients.


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