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
Background: The Intergroup 0116 and the MAGIC trials changed clinical practice for resectable gastric cancer in the Western world. In these trials, overall survival improved with post-operative... Show moreBackground: The Intergroup 0116 and the MAGIC trials changed clinical practice for resectable gastric cancer in the Western world. In these trials, overall survival improved with post-operative chemoradiotherapy (CRT) and perioperative chemotherapy (CT). Intention-to-treat analysis in the CRITICS trial of post-operative CT or post-operative CRT did not show a survival difference. The current study reports on the per-protocol (PP) analysis of the CRITICS trial.Patients and methods: The CRITICS trial was a randomized, controlled trial in which 788 patients with stage Ib-Iva resectable gastric or esophagogastric adenocarcinoma were included. Before start of preoperative CT, patients from the Netherlands, Sweden and Denmark were randomly assigned to receive post-operative CT or CRT. For the current analysis, only patients who started their allocated post-operative treatment were included. Since it is uncertain that the two treatment arms are balanced in such PP analysis, adjusted proportional hazards regression analysis and inverse probability weighted analysis were used to minimize the risk of selection bias and to estimate and compare overall and event-free survival.Results: Of the 788 patients, 478 started post-operative treatment according to protocol, 233 (59%) patients in the CT group and 245 (62%) patients in the CRT group. Patient and tumor characteristics between the groups before start of the post-operative treatment were not different. After a median follow-up of 6.7 years since the start of post-operative treatment, the 5-year overall survival was 57.9% (95% confidence interval: 51.4% to 64.3%) in the CT group versus 45.5% (95% confidence interval: 39.2% to 51.8%) in the CRT group (adjusted hazard ratio CRT versus CT: 1.62 (1.24-2.12), P = 0.0004). Inverse probability weighted analysis resulted in similar hazard ratios.Conclusion: After adjustment for all known confounding factors, the PP analysis of patients who started the allocated post-operative treatment in the CRITICS trial showed that the CT group had a significantly better 5-year overall survival than the CRT group (NCT00407186). Show less
Background. The radiation and concomitant high-dose intra-arterial or intravenous cisplatin (RADPLAT) phase III trial compared intra-arterial (IA) to intravenous (IV) cisplatin-based chemoradiation... Show moreBackground. The radiation and concomitant high-dose intra-arterial or intravenous cisplatin (RADPLAT) phase III trial compared intra-arterial (IA) to intravenous (IV) cisplatin-based chemoradiation for head and neck cancer. Long-term efficacy and toxicity are reported after a median follow-up of 7.5 years.Methods. Patients with inoperable squamous cell carcinoma (SCC) of the oropharynx, oral cavity, or hypopharynx, were randomized between radiotherapy (RT) + IA cisplatin 150 mg/m(2), followed by systemic rescue or RT + I. V. cisplatin 100 mg/m(2). RT consisted of 46 Gy to the affected and elective areas, followed by a boost of 24 Gy.Results. Among 237 patients, 57 recurred locally, 35 regionally, and 80 locoregionally. There were 32 second primary tumors, 65 distant metastases, and 154 deaths. Locoregional control and overall survival were not different between the treatment arms. Late dysphagia was worse in the I.V. arm (log-rank p=.014).Conclusion. IA cisplatin did not improve tumor control compared to I.V. administered cisplatin, despite the higher dose in IA delivery of the drug. (C) 2015 Wiley Periodicals, Inc. Show less
Theunissen, E.A.R.; Bosma, S.C.J.; Zuur, C.L.; Spijker, R.; Baan, S. van der; Dreschler, W.A.; ... ; Rasch, C.R.N. 2015
BackgroundBoth radiotherapy (RT) and cisplatin-based chemoradiotherapy (CRT) in patients with head and neck cancer may cause sensorineural hearing loss (SNHL). The purpose of this review was to... Show moreBackgroundBoth radiotherapy (RT) and cisplatin-based chemoradiotherapy (CRT) in patients with head and neck cancer may cause sensorineural hearing loss (SNHL). The purpose of this review was to provide more insight into SNHL because of CRT compared to RT.MethodsComprehensive search of Medline and Embase with the terms radiotherapy combined with ototoxicity, head and neck squamous cell carcinoma, and synonyms.ResultsOf the 2507 studies found, 21 were included in this study. Pooled analysis could not be committed because of heterogeneity. Incidence rates of SNHL after RT and CRT varied considerably, with percentages ranging from 0% to 43% and 17% to 88%, respectively. Factors that influenced the risk of SNHL were radiation dose to the cochlea, follow-up time, age, baseline hearing level, and cisplatin dose.ConclusionThe wide range of SNHL incidence rates makes it impossible to draw any conclusions on the severity of RT- and CRT-induced ototoxicity. To allow for future comparison of study outcomes, development of uniform criteria is of utmost importance. (c) 2014 Wiley Periodicals, Inc. Head Neck37: 281-292, 2015 Show less
