Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) is a rare, aggressive cutaneous lymphoma with a 5-year disease-specific survival of only --55%. Despite high response rates to... Show morePrimary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) is a rare, aggressive cutaneous lymphoma with a 5-year disease-specific survival of only --55%. Despite high response rates to initial immune-polychemotherapy, most patients experience a disease relapse. The genetic evolution of primary and relapsed/refractory disease has only scarcely been studied in PCDLBCL-LT patients. Therefore, in this retrospective cohort study, 73 primary/pre-treatment and relapsed/refractory biopsies of 57 patients with PCDLBCL-LT were molecularly characterized with triple FISH and targeted next-generation sequencing for 52 B-cell-lymphoma-relevant genes, including paired analysis in 16 patients. In this cohort, 95% of patients harboured at least one of the three main driver alterations (mutations in MYD88 /CD79B and/or CDKN2A-loss). In relapsed/refractory PCDLBCL-LT, these oncogenic aberrations were persistently present, demonstrating genetic stability over time. Novel alterations in relapsed disease affected mostly CDKN2A, MYC, and PIM1. Regarding survival, only MYC rearrangements and HIST1H1E mutations were statistically significantly associated with an inferior outcome. The stable presence of one or more of the three main driver alterations (mutated MYD88/ CD79B and/or CDKN2A-loss) is promising for targeted therapies addressing these alterations and serves as a rationale for molecular-based disease monitoring, improving response evaluation and early identification and intervention of disease relapses in these poor-prognostic PCDLBCL-LT patients. Show less
Objectives: We have developed two Dutch questionnaires to assess the shared decision-making (SDM) process in oncology; the iSHAREpatient and iSHAREphysician. In this study, we aimed to determine:... Show moreObjectives: We have developed two Dutch questionnaires to assess the shared decision-making (SDM) process in oncology; the iSHAREpatient and iSHAREphysician. In this study, we aimed to determine: scores, construct validity, test-retest agreement (iSHAREpatient), and inter-rater (iSHAREpatient-iSHAREphysician) agreement. Methods: Physicians from seven Dutch hospitals recruited cancer patients, and completed the iSHAREphysician and SDM-Questionnaire-physician version. Their patients completed the: iSHAREpatient, nine-item SDM-Questionnaire, Decisional Conflict Scale, Combined Outcome Measure for Risk communication And treatment Decision-making Effectiveness, and five-item Perceived Efficacy in Patient-Physician Interactions. We formulated, respectively, one (iSHAREphysician) and 10 (iSHAREpatient) a priori hypotheses regarding correlations between the iSHARE questionnaires and questionnaires assessing related constructs. To assess test-retest agreement patients completed the iSHAREpatient again 1-2 weeks later. Results: In total, 151 treatment decision-making processes with unique patients were rated. Dimension and total iSHARE scores were high both in patients and physicians. The hypothesis on the iSHAREphysician and 9/10 hypotheses on the iSHAREpatient were confirmed. Test-retest and inter-rater agreement were >.60 for most items. Conclusions: The iSHARE questionnaires show high scores, have good construct validity, substantial test-retest agreement, and moderate inter-rater agreement. Practice implications: Results from the iSHARE questionnaires can inform both physician- and patient-directed efforts to improve SDM in clinical practice. Show less
Neelis, K.J.; Kip, D.M.; Speetjens, F.M.; Linden, Y.M. van der 2022
Background and purpose To gain insight into the treatment outcomes for anal cancer a retrospective analysis was performed with a special emphasis on trends in outcome and toxicities over time and... Show moreBackground and purpose To gain insight into the treatment outcomes for anal cancer a retrospective analysis was performed with a special emphasis on trends in outcome and toxicities over time and on treatment of elderly patients. Materials and methods Medical records of 98 consecutive patients with squamous cell carcinoma of the anus of all stages treated with curative intent between 01-01-2009 and 31-12-2018 were analyzed with follow up until 31-12-2020. Standard tumor and pathological lymph node dose were 59.4 Gy (median 59.4 Gy, range 59.4-70 Gy) or 60 Gy (no deviation from intended dose), elective nodal regions were treated with 45 Gy (no deviations). Radiotherapy techniques in this period evolved from 3D-conformal to IMRT and VMAT. In 23 patients electron beams were used. Results Median age was 63 years (range 41-88), the majority of patients were female (60%). Twenty three patients were > 75 years old. The TNM stages were I, II, IIIA, and IIIB in 18%, 40%, 15% and 27%, 58% of patients had N0 status. Concurrent mitomycin C and 5-fluoruracil-based chemotherapy was given in 63 patients (64%). Five-year overall survival (OS), disease free survival (DFS), locoregional control (LRC) and colostomy free survival (CFS) were 71%, 80%, 82%, and 82% for the whole group. Results in patients > 75 years of age were not statistically different from those in younger patients. With the introduction of more conformal techniques DFS did not change and toxicities decreased. Conclusion Real word treatment outcomes per disease stage were in line with what is reported in literature. Older patients should also be offered treatment with curative intent. Show less
PURPOSE: The benefit of neoadjuvant chemoradiotherapy in resectable and borderline resectable pancreatic cancer remains controversial. Initial results of the PREOPANC trial failed to demonstrate a... Show morePURPOSE: The benefit of neoadjuvant chemoradiotherapy in resectable and borderline resectable pancreatic cancer remains controversial. Initial results of the PREOPANC trial failed to demonstrate a statistically significant overall survival (OS) benefit. The long-term results are reported. METHODS: In this multicenter, phase III trial, patients with resectable and borderline resectable pancreatic cancer were randomly assigned (1:1) to neoadjuvant chemoradiotherapy or upfront surgery in 16 Dutch centers. Neoadjuvant chemoradiotherapy consisted of three cycles of gemcitabine combined with 36 Gy radiotherapy in 15 fractions during the second cycle. After restaging, patients underwent surgery followed by four cycles of adjuvant gemcitabine. Patients in the upfront surgery group underwent surgery followed by six cycles of adjuvant gemcitabine. The primary outcome was OS by intention-to-treat. No safety data were collected beyond the initial report of the trial. RESULTS: Between April 24, 2013, and July 25, 2017, 246 eligible patients were randomly assigned to neoadjuvant chemoradiotherapy (n = 119) and upfront surgery (n = 127). At a median follow-up of 59 months, the OS was better in the neoadjuvant chemoradiotherapy group than in the upfront surgery group (hazard ratio, 0.73; 95% CI, 0.56 to 0.96; P = .025). Although the difference in median survival was only 1.4 months (15.7 months v 14.3 months), the 5-year OS rate was 20.5% (95% CI, 14.2 to 29.8) with neoadjuvant chemoradiotherapy and 6.5% (95% CI, 3.1 to 13.7) with upfront surgery. The effect of neoadjuvant chemoradiotherapy was consistent across the prespecified subgroups, including resectable and borderline resectable pancreatic cancer. CONCLUSION: Neoadjuvant gemcitabine-based chemoradiotherapy followed by surgery and adjuvant gemcitabine improves OS compared with upfront surgery and adjuvant gemcitabine in resectable and borderline resectable pancreatic cancer. Show less
PURPOSEThe benefit of neoadjuvant chemoradiotherapy in resectable and borderline resectable pancreatic cancer remains controversial. Initial results of the PREOPANC trial failed to demonstrate a... Show morePURPOSEThe benefit of neoadjuvant chemoradiotherapy in resectable and borderline resectable pancreatic cancer remains controversial. Initial results of the PREOPANC trial failed to demonstrate a statistically significant overall survival (OS) benefit. The long-term results are reported.METHODSIn this multicenter, phase III trial, patients with resectable and borderline resectable pancreatic cancer were randomly assigned (1:1) to neoadjuvant chemoradiotherapy or upfront surgery in 16 Dutch centers. Neoadjuvant chemoradiotherapy consisted of three cycles of gemcitabine combined with 36 Gy radiotherapy in 15 fractions during the second cycle. After restaging, patients underwent surgery followed by four cycles of adjuvant gemcitabine. Patients in the upfront surgery group underwent surgery followed by six cycles of adjuvant gemcitabine. The primary outcome was OS by intention-to-treat. No safety data were collected beyond the initial report of the trial.RESULTSBetween April 24, 2013, and July 25, 2017, 246 eligible patients were randomly assigned to neoadjuvant chemoradiotherapy (n = 119) and upfront surgery (n = 127). At a median follow-up of 59 months, the OS was better in the neoadjuvant chemoradiotherapy group than in the upfront surgery group (hazard ratio, 0.73; 95% CI, 0.56 to 0.96; P = .025). Although the difference in median survival was only 1.4 months (15.7 months v 14.3 months), the 5-year OS rate was 20.5% (95% CI, 14.2 to 29.8) with neoadjuvant chemoradiotherapy and 6.5% (95% CI, 3.1 to 13.7) with upfront surgery. The effect of neoadjuvant chemoradiotherapy was consistent across the prespecified subgroups, including resectable and borderline resectable pancreatic cancer.CONCLUSIONNeoadjuvant gemcitabine-based chemoradiotherapy followed by surgery and adjuvant gemcitabine improves OS compared with upfront surgery and adjuvant gemcitabine in resectable and borderline resectable pancreatic cancer. Show less
Purpose: Total skin electron beam therapy (TSEBT) is used mostly in the treatment of cutaneous T cell lymphoma. In this study we describe the results of TSEBT applied in the Netherlands using two... Show morePurpose: Total skin electron beam therapy (TSEBT) is used mostly in the treatment of cutaneous T cell lymphoma. In this study we describe the results of TSEBT applied in the Netherlands using two different schedules, a conventional dose schedule of 35 Gy and a low-dose schedule of 12 Gy. We aimed to evaluate the treatment results in and compare treatment outcomes between the two treatment groups and to further define indications for both doses.Methods: In the LUMC, Leiden, we performed a retrospective analysis of 51 patients treated with TSEBT between January 2008 and December 2018, with follow-up untill December 2019. Thirty one patients were treated with 35 Gy and twenty with 12 Gy. The dose was chosen based on the severity of skin involvement. Outcome measures were time to meaningful progression, survival, response rate and toxicity.Results: Time to meaningful progression was 5.1 months with no significant differences between dose groups (P = 0.77). Overall survival was 27.4 months. Both time to progression and survival were significantly better for T2 vs T3 stage. Overall response rate was 80.4 %. Both dose groups showed improvement of symptoms. Treatment was generally well tolerated.Conclusions: Both high-dose and low-dose TSEBT offer similar results for TMP and OS. It remains unclear which patients benefit most from a high-dose schedule. We propose to use the low-dose schedule as a standard for TSEBT and use supplementary boosts or escalation to high-dose treatment for patients unresponsive to the low-dose schedule. Show less
Holstein, Y. van; Trompet, S.; Deudekom, F.J. van; Munster, B. van; Glas, N.A. de; Bos, F. van den; ... ; Mooijaart, S.P. 2022
Background: Patients with potentially curable esophageal cancer can be treated with neo-adjuvant chemoradiotherapy followed by surgery or definitive chemoradiotherapy with curative intent. For... Show moreBackground: Patients with potentially curable esophageal cancer can be treated with neo-adjuvant chemoradiotherapy followed by surgery or definitive chemoradiotherapy with curative intent. For frail older patients choosing the appropriate oncological treatment can be difficult, and data on geriatric deficits as determinants of treatment outcomes are not yet available. Objectives: To describe the prevalence of geriatric deficits and to study their association with treatment discontinuation and mortality in older patients with potentially curable esophageal cancer. Material and Methods: A cohort study was conducted in a Dutch tertiary care hospital including patients aged >= 70 years with primary stage I-IVA esophageal cancer. Geriatric screening and assessment data were collected. Outcomes were treatment discontinuation and one year all-cause mortality. Results: In total, 138 patients with curable esophageal cancer were included. Mean age was 76.1 years (standard deviation 4.7), 54% had clinical stage III and 24% stage IVA disease. Most patients received neo-adjuvant chemoradiotherapy and surgery (41%), 32% definitive chemoradiotherapy and 22% palliative radiotherapy. Overall, one year all-cause mortality was 36%. Geriatric screening and assessment was performed in 94 out of 138 patients, of which 60% was malnourished, 20% dependent in Instrumental Activities of Daily Living (IADL) and 52% was frail. Malnutrition was associated with higher mortality risk (Hazard Ratio, 3.2; 95% Confidence Interval, 1.3-7.7)) independent of age, sex and tumor stage. Seventy-six out of 94 patients were treated with chemoradiotherapy, of which 23% discontinued treatment. Patients with IADL dependency and Charlson Comorbidity Index >= 1 discontinued treatment more often. Conclusion: All-cause mortality within one year was high, irrespective of treatment modality. Treatment discontinuation rate was high, especially in patients treated with definitive chemoradiotherapy. Geriatric assessment associates with outcomes in older patients with esophageal cancer and may inform treatment decisions and optimization in future patients, but more research is needed to establish its predictive value. Show less
Cloos-van Balen, M.; Portier, E.S.H.; Fiocco, M.; Hartgrink, H.H.; Langers, A.M.J.; Neelis, K.J.; ... ; Slingerland, M. 2021
Background and objectives Since the first results of the Dutch randomized CROSS-trial, neoadjuvant chemoradiotherapy (CRT) using carboplatin and paclitaxel followed by resection for primary... Show moreBackground and objectives Since the first results of the Dutch randomized CROSS-trial, neoadjuvant chemoradiotherapy (CRT) using carboplatin and paclitaxel followed by resection for primary resectable nonmetastatic esophageal cancer (EC) has been implemented as standard curative treatment in the Netherlands. The purpose of this retrospective study is to evaluate the clinical outcomes of this treatment in daily practice in a large academic hospital. Methods Medical records of patients treated for primary resectable nonmetastatic EC between May 2010 and December 2015 at our institution were reviewed. Treatment consisted of five weekly courses of carboplatin (area under the curve 2) and paclitaxel (50 mg/m(2)) with concurrent external beam radiotherapy (23 fractions of 1.8 Gy), followed by transthoracic or transhiatal resection. Data on survival, progression, acute and late toxicity were recorded. Results A total of 145 patients were included. Median follow-up was 43 months. Median overall survival (OS) and progression-free survival (PFS) were 35 (95% confidence interval [CI] 29.8-40.2) and 30 (95% CI 19.7-40.3) months, respectively, with corresponding 3-year OS and PFS of 49.6% (95% CI 40.4-58.8) and 45.6% (95% CI 36.6-54.6). Acute toxicity grade >= 3 was observed in 25.5% of patients. Late adverse events grade >= 3 were seen in 24.8%, mostly esophageal stenosis. Conclusion Neoadjuvant CRT followed by resection for primary resectable nonmetastatic EC in daily practice results in a 3-year OS of 49.6% (95% CI 40.4-58.8) and PFS of 45.6% (95% CI 36.6-54.6), compared with 58% (51-65%) and 51% (43-58%) within the CROSS-trial. The slightly poorer survival in our daily practice group might be due to the presence of less favorable patient and tumor characteristics in daily practice, as is to be expected in daily practice. Toxicity was comparable with that in the CROSS-trial and considered acceptable. Show less
Cloos-van Balen, M.; Portier, E.S.H.; Fiocco, M.; Hartgrink, H.H.; Langers, A.M.J.; Neelis, K.J.; ... ; Slingerland, M. 2021
Background and objectivesSince the first results of the Dutch randomized CROSS-trial, neoadjuvant chemoradiotherapy (CRT) using carboplatin and paclitaxel followed by resection for primary... Show moreBackground and objectivesSince the first results of the Dutch randomized CROSS-trial, neoadjuvant chemoradiotherapy (CRT) using carboplatin and paclitaxel followed by resection for primary resectable nonmetastatic esophageal cancer (EC) has been implemented as standard curative treatment in the Netherlands. The purpose of this retrospective study is to evaluate the clinical outcomes of this treatment in daily practice in a large academic hospital.MethodsMedical records of patients treated for primary resectable nonmetastatic EC between May 2010 and December 2015 at our institution were reviewed. Treatment consisted of five weekly courses of carboplatin (area under the curve 2) and paclitaxel (50 mg/m2) with concurrent external beam radiotherapy (23 fractions of 1.8 Gy), followed by transthoracic or transhiatal resection. Data on survival, progression, acute and late toxicity were recorded.ResultsA total of 145 patients were included. Median follow-up was 43 months. Median overall survival (OS) and progression-free survival (PFS) were 35 (95% confidence interval [CI] 29.8–40.2) and 30 (95% CI 19.7–40.3) months, respectively, with corresponding 3-year OS and PFS of 49.6% (95% CI 40.4–58.8) and 45.6% (95% CI 36.6–54.6). Acute toxicity grade ≥3 was observed in 25.5% of patients. Late adverse events grade ≥3 were seen in 24.8%, mostly esophageal stenosis.ConclusionNeoadjuvant CRT followed by resection for primary resectable nonmetastatic EC in daily practice results in a 3-year OS of 49.6% (95% CI 40.4–58.8) and PFS of 45.6% (95% CI 36.6–54.6), compared with 58% (51–65%) and 51% (43–58%) within the CROSS-trial. The slightly poorer survival in our daily practice group might be due to the presence of less favorable patient and tumor characteristics in daily practice, as is to be expected in daily practice. Toxicity was comparable with that in the CROSS-trial and considered acceptable. Show less
Kleef, J.J. van; Dijksterhuis, W.P.M.; Boorn, H.G. van den; Prins, M.; Verhoeven, R.H.A.; Gisbertz, S.S.; ... ; Dutch Upper GI Canc Grp DUCG 2021
Background Accumulating evidence of trials demonstrates that patient-reported health-related quality of life (HRQoL) at diagnosis is prognostic for overall survival (OS) in oesophagogastric cancer.... Show moreBackground Accumulating evidence of trials demonstrates that patient-reported health-related quality of life (HRQoL) at diagnosis is prognostic for overall survival (OS) in oesophagogastric cancer. However, real-world data are lacking. Moreover, differences in disease stages and tumour-specific symptoms are usually not taken into consideration. The aim of this population-based study was to assess the prognostic value of HRQoL, including tumour-specific scales, on OS in patients with potentially curable and advanced oesophagogastric cancer. Methods Data were derived from the Netherlands Cancer Registry and the patient reported outcome registry (POCOP). Patients included in POCOP between 2016 and 2018 were stratified for potentially curable (cT1-4aNallM0) or advanced (cT4b or cM1) disease. HRQoL was measured with the EORTC QLQ-C30 and the tumour-specific OG25 module. Cox proportional hazards models assessed the impact of HRQoL, sociodemographic and clinical factors (including treatment) on OS. Results In total, 924 patients were included. Median OS was 38.9 months in potentially curable patients (n = 795) and 10.6 months in patients with advanced disease (n = 129). Global Health Status was independently associated with OS in potentially curable patients (HR 0.89, 99%CI 0.82-0.97), together with several other HRQoL items: appetite loss, dysphagia, eating restrictions, odynophagia, and body image. In advanced disease, the Summary Score was the strongest independent prognostic factor (HR 0.75, 99%CI 0.59-0.94), followed by fatigue, pain, insomnia and role functioning. Conclusion In a real-world setting, HRQoL was prognostic for OS in patients with potentially curable and advanced oesophagogastric cancer. Several HRQoL domains, including the Summary Score and several OG25 items, could be used to develop or update prognostic models. Show less
PURPOSE Preoperative chemoradiotherapy may improve the radical resection rate for resectable or borderline resectable pancreatic cancer, but the overall benefit is unproven.PATIENTS AND METHODS In... Show morePURPOSE Preoperative chemoradiotherapy may improve the radical resection rate for resectable or borderline resectable pancreatic cancer, but the overall benefit is unproven.PATIENTS AND METHODS In this randomized phase III trial in 16 centers, patients with resectable or borderline resectable pancreatic cancer were randomly assigned to receive preoperative chemoradiotherapy, which consisted of 3 courses of gemcitabine, the second combined with 15 x 2.4 Gy radiotherapy, followed by surgery and 4 courses of adjuvant gemcitabine or to immediate surgery and 6 courses of adjuvant gemcitabine. The primary end point was overall survival by intention to treat.RESULTS Between April 2013 and July 2017, 246 eligible patients were randomly assigned; 119 were assigned to preoperative chemoradiotherapy and 127 to immediate surgery. Median overall survival by intention to treat was 16.0 months with preoperative chemoradiotherapy and 14.3 months with immediate surgery (hazard ratio, 0.78; 95% CI, 0.58 to 1.05; P = .096). The resection rate was 61% and 72% (P = .058). The R0 resection rate was 71% (51 of 72) in patients who received preoperative chemoradiotherapy and 40% (37 of 92) in patients assigned to immediate surgery (P < .001). Preoperative chemoradiotherapy was associated with significantly better disease-free survival and locoregional failure-free interval as well as with significantly lower rates of pathologic lymph nodes, perineural invasion, and venous invasion. Survival analysis of patients who underwent tumor resection and started adjuvant chemotherapy showed improved survival with preoperative chemoradiotherapy (35.2 v 19.8 months; P = .029). The proportion of patients who suffered serious adverse events was 52% versus 41% (P = .096).CONCLUSION Preoperative chemoradiotherapy for resectable or borderline resectable pancreatic cancer did not show a significant overall survival benefit. Although the outcomes of the secondary end points and predefined subgroup analyses suggest an advantage of the neoadjuvant approach, additional evidence is required. Show less
Walterbos, N.R.; Fiocco, M.; Neelis, K.J.; Linden, Y.M. van der; Langers, A.M.J.; Slingerland, M.; ... ; Lips, I.M. 2019
Background and purposeAccurate delineation of the primary tumour is vital to the success of radiotherapy and even more important for successful boost strategies, aiming for improved local control... Show moreBackground and purposeAccurate delineation of the primary tumour is vital to the success of radiotherapy and even more important for successful boost strategies, aiming for improved local control in oesophageal cancer patients. Therefore, the aim was to assess delineation variability of the gross tumour volume (GTV) between CT and combined PET-CT in oesophageal cancer patients in a multi-institutional study.Materials and methodsTwenty observers from 14 institutes delineated the primary tumour of 6 cases on CT and PET-CT fusion. The delineated volumes, generalized conformity index (CIgen) and standard deviation (SD) in position of the most cranial/caudal slice over the observers were evaluated. For the central delineated region, perpendicular distance between median surface GTV and each individual GTV was evaluated as in-slice SD.ResultsAfter addition of PET, mean GTVs were significantly smaller in 3 cases and larger in 1 case. No difference in CIgen was observed (average 0.67 on CT, 0.69 on PET-CT). On CT cranial-caudal delineation variation ranged between 0.2 and 1.5 cm SD versus 0.2 and 1.3 cm SD on PET-CT. After addition of PET, the cranial and caudal variation was significantly reduced in 1 and 2 cases, respectively. The in-slice SD was on average 0.16 cm in both phases.ConclusionIn some cases considerable GTV delineation variability was observed at the cranial-caudal border. PET significantly influenced the delineated volume in four out of six cases, however its impact on observer variation was limited. Show less
