Predicting Long-term Disease-free Survival After Resection of Pancreatic Ductal Adenocarcinoma: A Nationwide Cohort Study.

OBJECTIVE: To develop a prediction model for long-term (≥5 years) disease-free survival (DFS) after the resection of pancreatic ductal adenocarcinoma (PDAC). BACKGROUND: Despite high recurrence rates, ~10% of patients have long-term DFS after PDAC resection. A model to predict long-term DFS may aid individualized prognostication and shared decision-making. METHODS: This nationwide cohort study included all consecutive patients who underwent PDAC resection in the Netherlands (2014-2016). The best-performing prognostic model was selected by Cox-proportional hazard analysis and Akaike's Information Criterion, presented by hazard ratios (HRs) with 95% confidence intervals (CIs). Internal validation was performed, and discrimination and calibration indices were assessed. RESULTS: In all, 836 patients with a median follow-up of 67 months (interquartile range 51-79) were analyzed. Long-term DFS was seen in 118 patients (14%). Factors predictive of long-term DFS were low preoperative carbohydrate antigen 19-9 (logarithmic; HR 1.21; 95% CI 1.10-1.32), no vascular resection (HR 1.33; 95% CI 1.12-1.58), T1 or T2 tumor stage (HR 1.52; 95% CI 1.14-2.04, and HR 1.17; 95% CI 0.98-1.39, respectively), well/moderate tumor differentiation (HR 1.44; 95% CI 1.22-1.68), absence of perineural and lymphovascular invasion (HR 1.42; 95% CI 1.11-1.81 and HR 1.14; 95% CI 0.96-1.36, respectively), N0 or N1 nodal status (HR 1.92; 95% CI 1.54-2.40, and HR 1.33; 95% CI 1.11-1.60, respectively), R0 resection margin status (HR 1.25; 95% CI 1.07-1.46), no major complications (HR 1.14; 95% CI 0.97-1.35) and adjuvant chemotherapy (HR 1.74; 95% CI 1.47-2.06). Moderate performance (concordance index 0.68) with adequate calibration (slope 0.99) was achieved. CONCLUSIONS: The developed prediction model, readily available at www.pancreascalculator.com, can be used to estimate the probability of long-term DFS after resection of pancreatic ductal adenocarcinoma.

The Value of Biological and Conditional Factors for Staging of Patients with Resectable Pancreatic Cancer Undergoing Upfront Resection: A Nationwide Analysis.

BACKGROUND: Novel definitions suggest that resectability status for pancreatic ductal adenocarcinoma (PDAC) should be assessed beyond anatomical criteria, considering both biological and conditional factors. This has, however, yet to be validated on a nationwide scale. This study evaluated the prognostic value of biological and conditional factors for staging of patients with resectable PDAC. PATIENTS AND METHODS: A nationwide observational cohort study was performed, including all consecutive patients who underwent upfront resection of National Comprehensive Cancer Network resectable PDAC in the Netherlands (2014-2019) with complete information on preoperative carbohydrate antigen (CA) 19-9 and Eastern Cooperative Oncology Group (ECOG) performance status. PDAC was considered biologically unfavorable (RB+) if CA19-9 ≥ 500 U/mL and favorable (RB-) otherwise. ECOG ≥ 2 was considered conditionally unfavorable (RC+) and favorable otherwise (RC-). Overall survival (OS) was assessed using Kaplan-Meier and Cox-proportional hazard analysis, presented as hazard ratios (HRs) with 95% confidence interval (CI). RESULTS: Overall, 688 patients were analyzed with a median overall survival (OS) of 20 months (95% CI 19-23). OS was 14 months (95% CI 10 months-median not reached) in 20 RB+C+ patients (3%; HR 1.61, 95% CI 0.86-2.70), 13 months (95% CI 11-15) in 156 RB+C- patients (23%; HR 1.86, 95% CI 1.50-2.31), and 21 months (95% CI 12-41) in 47 RB-C+ patients (7%; HR 1.14, 95% CI 0.80-1.62) compared with 24 months (95% CI 22-27) in 465 patients with RB-C- PDAC (68%; reference). CONCLUSIONS: Survival after upfront resection of anatomically resectable PDAC is worse in patients with CA19-9 ≥ 500 U/mL, while performance status had no impact. This supports consideration of CA19-9 in preoperative staging of resectable PDAC.

Outcome of Pancreatic Surgery During the First 6 Years of a Mandatory Audit Within the Dutch Pancreatic Cancer Group.

OBJECTIVE: To describe outcome after pancreatic surgery in the first 6 years of a mandatory nationwide audit. BACKGROUND: Within the Dutch Pancreatic Cancer Group, efforts have been made to improve outcome after pancreatic surgery. These include collaborative projects, clinical auditing, and implementation of an algorithm for early recognition and management of postoperative complications. However, nationwide changes in outcome over time have not yet been described. METHODS: This nationwide cohort study included consecutive patients after pancreatoduodenectomy (PD) and distal pancreatectomy from the mandatory Dutch Pancreatic Cancer Audit (January 2014-December 2019). Patient, tumor, and treatment characteristics were compared between 3 time periods (2014-2015, 2016-2017, and 2018-2019). Short-term surgical outcome was investigated using multilevel multivariable logistic regression analyses. Primary endpoints were failure to rescue (FTR) and in-hospital mortality. RESULTS: Overall, 5345 patients were included, of whom 4227 after PD and 1118 after distal pancreatectomy. After PD, FTR improved from 13% to 7.4% [odds ratio (OR) 0.64, 95% confidence interval (CI) 0.50-0.80, P <0.001] and in-hospital mortality decreased from 4.1% to 2.4% (OR 0.68, 95% CI 0.54-0.86, P =0.001), despite operating on more patients with age >75 years (18%-22%, P =0.006), American Society of Anesthesiologists score ≥3 (19%-31%, P <0.001) and Charlson comorbidity score ≥2 (24%-34%, P <0.001). The rates of textbook outcome (57%-55%, P =0.283) and major complications remained stable (31%-33%, P =0.207), whereas complication-related intensive care admission decreased (13%-9%, P =0.002). After distal pancreatectomy, improvements in FTR from 8.8% to 5.9% (OR 0.65, 95% CI 0.30-1.37, P =0.253) and in-hospital mortality from 1.6% to 1.3% (OR 0.88, 95% CI 0.45-1.72, P =0.711) were not statistically significant. CONCLUSIONS: During the first 6 years of a nationwide audit, in-hospital mortality and FTR after PD improved despite operating on more high-risk patients. Several collaborative efforts may have contributed to these improvements.

Timing of rectal cancer surgery after short-course radiotherapy: national database study.

BACKGROUND: Previous randomized trials found that a prolonged interval between short-course radiotherapy (SCRT, 25 Gy in 5 fractions) and surgery for rectal cancer (4-8 weeks, SCRT-delay) results in a lower postoperative complication rate and a higher pCR rate than SCRT and surgery within a week (SCRT-direct surgery). This study sought to confirm these results in a Dutch national database. METHODS: Patients with intermediate-risk rectal cancer (T3(mesorectal fascia (MRF)-) N0 M0 and T1-3(MRF-) N1 M0) treated with either SCRT-delay (4-12 weeks) or SCRT-direct surgery in 2018-2021 were selected from a Dutch national colorectal cancer database. Confounders were adjusted for using inverse probability of treatment weighting (IPTW). The primary endpoint was the 90-day postoperative complication rate. Secondary endpoints included the pCR rate. Endpoints were compared using log-binomial and Poisson regression. RESULTS: Some 664 patients were included in the SCRT-direct surgery and 238 in the SCRT-delay group. After IPTW, the 90-day postoperative complication rate was comparable after SCRT-direct surgery and SCRT-delay (40.1 versus 42.3 per cent; risk ratio (RR) 1.1, 95 per cent c.i. 0.9 to 1.3). A pCR occurred more often after SCRT-delay than SCRT-direct surgery (10.7 versus 0.4 per cent; RR 39, 11 to 139). CONCLUSION: There was no difference in surgical complication rates between SCRT-delay and SCRT-direct, but SCRT-delay was associated with more patients having a pCR.

Pelvic insufficiency fractures and pelvic bone metastases after neoadjuvant (chemo)radiotherapy for rectal cancer.

BACKGROUND: Pelvic insufficiency fractures (PIFs) are a late complication of radiotherapy for pelvic malignancies. We evaluated the incidence, radiologic findings, clinical course, and outcome of PIFs in patients treated with neoadjuvant (chemo)radiotherapy ((C)RT) for rectal cancer. MATERIAL AND METHODS: Data of patients diagnosed with rectal cancer from a large teaching hospital treated from 2002 to 2012 were extracted from the Dutch Cancer Registry. All hospital records were reviewed for the diagnosis of PIFs or pelvic bone metastases. An expert radiologist reassessed all imaging procedures of the lower back, abdomen, and pelvis. RESULTS: A total of 513 rectal cancer patients were identified of whom 300 patients (58.5%) were treated with neoadjuvant (C)RT (long- vs. short-course radiotherapy: 91 patients [17.7%] vs. 209 [40.7%], respectively). Twelve PIFs were diagnosed initially according to hospital records and imaging reports of all 513 patients. These 12 patients were treated with neoadjuvant (C)RT. After reassessment of all pelvic imaging procedures done in this patient group (432 patients (84.2%)), 20 additional PIFs were detected in patients treated with neoadjuvant (C)RT, resulting in a 10.7% PIF rate in irradiated patients. One PIF was detected in the group of patients not treated with neoadjuvant (C)RT for rectal cancer. This patient had palliative radiotherapy for prostate cancer and is left out of the analysis. Median follow-up time of 32 PIF patients was 49 months. Median time between start of neoadjuvant (C)RT and diagnosis of PIF was 17 months (IQR 9-28). Overall median survival for patients with PIF was 63.5 months (IQR 44-120). CONCLUSION: PIFs are a relatively common late complication of neoadjuvant (C)RT for rectal cancer but are often missed or misdiagnosed as pelvic bone metastases. The differentiation of PIFs from pelvic bone metastases is important because of a different treatment and disease outcome.

Patient- and physician-reported radiation-induced toxicity of short-course radiotherapy with a prolonged interval to surgery for rectal cancer.

AIM: A prolonged interval (>4 weeks) between short-course radiotherapy (25 Gy in five fractions) (SCRT-delay) and total mesorectal excision for rectal cancer has been associated with a decreased postoperative complication rate and offers the possibility of organ preservation in the case of a complete tumour response. This prospective cohort study systematically evaluated patient-reported bowel dysfunction and physician-reported radiation-induced toxicity for 8 weeks following SCRT-delay. METHOD: Patients who were referred for SCRT-delay for intermediate risk, oligometastatic or locally advanced rectal cancer were included. Repeated measurements were done for patient-reported bowel dysfunction (measured by the low anterior resection syndrome [LARS] questionnaire and categorized as no, minor or major LARS) and physician-reported radiation-induced toxicity (according to Common Terminology Criteria for Adverse Events version 4.0) before start of treatment (baseline), at completion of SCRT and 1, 2, 3, 4, 6 and 8 weeks thereafter. RESULTS: Fifty-one patients were included; 31 (61%) were men and the median age was 67 years (range 44-91). Patient-reported bowel dysfunction and physician-reported radiation-induced toxicity peaked at weeks 1-2 after completion of SCRT and gradually declined thereafter. Major LARS was reported by 44 patients (92%) at some time during SCRT-delay. Grade 3 radiation-induced toxicity was reported in 17 patients (33%) and concerned predominantly diarrhoea. No Grade 4-5 radiation-induced toxicity occurred. CONCLUSION: During SCRT-delay, almost every patient experiences temporary mild-moderate radiation-induced toxicity and major LARS, but life-threatening toxicity is rare. SCRT-delay is a safe alternative to SCRT-direct surgery that should be proposed when counselling rectal cancer patients on neoadjuvant strategies.

Detection, Treatment, and Survival of Pancreatic Cancer Recurrence in the Netherlands: A Nationwide Analysis.

OBJECTIVE: To evaluate whether detection of recurrent pancreatic ductal adenocarcinoma (PDAC) in an early, asymptomatic stage increases the number of patients receiving additional treatment, subsequently improving survival. SUMMARY OF BACKGROUND DATA: International guidelines disagree on the value of standardized postoperative surveillance for early detection and treatment of PDAC recurrence. METHODS: A nationwide, observational cohort study was performed including all patients who underwent PDAC resection (2014-2016). Prospective baseline and perioperative data were retrieved from the Dutch Pancreatic Cancer Audit. Data on follow-up, treatment, and survival were collected retrospectively. Overall survival (OS) was evaluated using multivariable Cox regression analysis, before and after propensity-score matching, stratified for patients with symptomatic and asymptomatic recurrence. RESULTS: Eight hundred thirty-six patients with a median follow-up of 37 months (interquartile range 30-48) were analyzed. Of those, 670 patients (80%) developed PDAC recurrence after a median follow-up of 10 months (interquartile range 5-17). Additional treatment was performed in 159/511 patients (31%) with symptomatic recurrence versus 77/159 (48%) asymptomatic patients (P < 0.001). After propensity-score matching on lymph node ratio, adjuvant therapy, disease-free survival, and recurrence site, additional treatment was independently associated with improved OS for both symptomatic patients [hazard ratio 0.53 (95% confidence interval 0.42-0.67); P < 0.001] and asymptomatic patients [hazard ratio 0.45 (95% confidence interval 0.29-0.70); P < 0.001]. CONCLUSIONS: Additional treatment of PDAC recurrence was independently associated with improved OS, with asymptomatic patients having a higher probability to receive recurrence treatment. Therefore, standardized postoperative surveillance aiming to detect PDAC recurrence before the onset of symptoms has the potential to improve survival. This provides a rationale for prospective studies on standardized surveillance after PDAC resection.

Nationwide Validation of the 8th American Joint Committee on Cancer TNM Staging System and Five Proposed Modifications for Resected Pancreatic Cancer.

BACKGROUND: The prognostic value of four proposed modifications to the 8th American Joint Committee on Cancer (AJCC) TNM staging system has yet to be evaluated. This study aimed to validate five proposed modifications. METHODS: Patients who underwent pancreatic ductal adenocarcinoma resection (2014-2016), as registered in the prospective Dutch Pancreatic Cancer Audit, were included. Stratification and prognostication of TNM staging systems were assessed using Kaplan-Meier curves, Cox proportional hazard analyses, and C-indices. A new modification was composed based on overall survival (OS). RESULTS: Overall, 750 patients with a median OS of 18 months (interquartile range 10-32) were included. The 8th edition had an increased discriminative ability compared with the 7th edition {C-index 0.59 (95% confidence interval [CI] 0.56-0.61) vs. 0.56 (95% CI 0.54-0.58)}. Although the 8th edition showed a stepwise decrease in OS with increasing stage, no differences could be demonstrated between all substages; stage IIA vs. IB (hazard ratio [HR] 1.30, 95% CI 0.80-2.09; p  = 0.29) and stage IIB vs. IIA (HR 1.17, 95% CI 0.75-1.83; p  = 0.48). The four modifications showed comparable prognostic accuracy (C-index 0.59-0.60); however, OS did not differ between all modified TNM stages (ns). The new modification, migrating T3N1 patients to stage III, showed a C-index of 0.59, but did detect significant survival differences between all TNM stages (p  < 0.05). CONCLUSIONS: The 8th TNM staging system still lacks prognostic value for some categories of patients, which was not clearly improved by four previously proposed modifications. The modification suggested in this study allows for better prognostication in patients with all stages of disease.

Online adaptive MR-guided stereotactic radiotherapy for unresectable malignancies in the upper abdomen using a 1.5T MR-linac.

BACKGROUND: Introduction of online adaptive MR-guided radiotherapy enables stereotactic body radiation therapy (SBRT) of upper abdominal tumors. This study aimed to evaluate the feasibility of MR-guided SBRT on a 1.5 T MR-linac in patients with unresectable upper abdominal malignancies. MATERIAL AND METHODS: Patients treated at the UMC Utrecht (April 2019 to December 2020) were identified in the prospective 'Multi-OutcoMe EvaluatioN of radiation Therapy Using the MR-linac' (MOMENTUM) study. Feasibility of treatment was arbitrarily defined as an on-table time interval of ≤60 min for >75% of delivered fractions and completion of >95% of fractions as scheduled, reflecting patient tolerability. Acute treatment-related toxicity was assessed at 3 months of follow-up and graded according to the National Cancer Institute Common Terminology Criteria of Adverse Events version 5.0. RESULTS: Twenty-five consecutive patients with a median follow-up time of 8 (range 4-23) months were treated with 35 Gray (n = 4) and 40 Gray (n = 21) in five fractions over 2 weeks. For all fractions, contours were adapted based on the daily anatomy and delivered within 47 min/fraction (range 30-74). In 98/117 fractions (84%), adapted treatment was completed within 1 h. All patients received the scheduled irradiation dose as planned. No acute grade 3 toxicity or higher was reported. Treatment resulted in pain alleviation in 11/13 patients. DISCUSSION: Online adaptive MR-guided SBRT on a 1.5 T MR-linac is feasible and well-tolerated in patients with unresectable upper abdominal malignancies. Dose escalation studies, followed by comparative studies, are needed to determine the optimal radiation dose for irradiation of upper abdominal malignancies.

Preoperative predictors for early and very early disease recurrence in patients undergoing resection of pancreatic ductal adenocarcinoma.

BACKGROUND: This study aimed to identify predictors for early and very early disease recurrence in patients undergoing resection of pancreatic ductal adenocarcinoma (PDAC) resection with and without neoadjuvant therapy. METHODS: Included were patients who underwent PDAC resection (2014-2016). Multivariable multinomial regression was performed to identify preoperative predictors for manifestation of recurrence within 3, 6 and 12 months after PDAC resection. RESULTS: 836 patients with a median follow-up of 37 (interquartile range [IQR] 30-48) months and overall survival of 18 (IQR 10-32) months were analyzed. 670 patients (80%) developed recurrence: 82 patients (10%) <3 months, 96 patients (11%) within 3-6 months and 226 patients (27%) within 6-12 months. LogCA 19-9 (OR 1.25 [95% CI 1.10-1.41]; P < 0.001) and neoadjuvant treatment (OR 0.09 [95% CI 0.01-0.68]; P = 0.02) were associated with recurrence <3 months. LogCA 19-9 (OR 1.23 [95% CI 1.10-1.38]; P < 0.001) and 0-90° venous involvement on CT imaging (OR 2.93 [95% CI 1.60-5.37]; P < 0.001) were associated with recurrence within 3-6 months. A Charlson Age Comorbidity Index ≥4 (OR 1.53 [95% CI 1.09-2.16]; P = 0.02) and logCA 19-9 (OR 1.24 [95% CI 1.14-1.35]; P < 0.001) were related to recurrence within 6-12 months. CONCLUSION: This study demonstrates preoperative predictors that are associated with the manifestation of early and very early recurrence after PDAC resection. Knowledge of these predictors can be used to guide individualized surveillance and treatment strategies.

Progression-free survival in patients with 68Ga-PSMA-PET-directed SBRT for lymph node oligometastases.

BACKGROUND: Prostate cancer oligometastatic disease can be treated using stereotactic body radiotherapy (SBRT) in order to postpone start of systemic treatments such as androgen deprivation therapy (ADT). 68Ga-PSMA-PET/CT imaging allows for diagnosis of oligometastases at lower PSA values. We analysed a cohort of patients with prostate cancer lymph node oligometastases detected on PSMA-PET/CT. MATERIALS AND METHODS: Ninety patients with metachronous oligometastatic prostate cancer received SBRT for 1-3 lymph node metastases diagnosed on 68Ga-PSMA-PET/CT. The primary end point was progression free survival (PFS), with disease progression defined as occurrence of either target lesion progression, new metastatic lesion or biochemical progression. Secondary outcomes were biochemical PFS (BPFS), ADT-free survival (ADT-FS), toxicity and quality of life (QoL). Baseline patient characteristics were tested for association with PFS and a preliminary risk score was created. RESULTS: Median follow-up was 21 months (interquartile range 10-31 months). Median PFS and BPFS were 16 and 21 months, respectively. Median ADT-FS was not reached (73% (95%-CI 62-86%) at 24 months). In multivariable analysis, younger age, higher PSA prior to SBRT and extrapelvic location were associated with shorter PFS. Grade 1 fatigue was the most predominant acute toxicity (34%). Highest grade toxicity was grade 2 for acute and late events. QoL analysis showed mild, transient increase in fatigue at 1-4 weeks after SBRT. CONCLUSION: A median PFS of 16 months was attained after SBRT for patients with PSMA-PET positive oligometastatic lymph nodes from prostate cancer. Higher pre-SBRT PSA, younger age and extrapelvic location were found to be predictors of shorter PFS.

A field strength independent MR radiomics model to predict pathological complete response in locally advanced rectal cancer.

PURPOSE: Aim of this study was to develop a generalised radiomics model for predicting pathological complete response after neoadjuvant chemo-radiotherapy in locally advanced rectal cancer patients using pre-CRT T2-weighted images acquired at a 1.5 T and a 3 T scanner. METHODS: In two institutions, 195 patients were scanned: 136 patients were scanned on a 1.5 T MR scanner, 59 patients on a 3 T MR scanner. Gross tumour volumes were delineated on the MR images and 496 radiomic features were extracted, applying the intensity-based (IB) filter. Features were standardised with Z-score normalisation and an initial feature selection was carried out using Wilcoxon-Mann-Whitney test: The most significant features at 1.5 T and 3 T were selected as main features. Several logistic regression models combining the main features with a third one selected by those resulting significant were elaborated and evaluated in terms of area under curve (AUC). A tenfold cross-validation was repeated 300 times to evaluate the model robustness. RESULTS: Three features were selected: maximum fractal dimension with IB = 0-50, energy and grey-level non-uniformity calculated on the run-length matrix with IB = 0-50. The AUC of the model applied to the whole dataset after cross-validation was 0.72, while values of 0.70 and 0.83 were obtained when 1.5 T and 3 T patients were considered, respectively. CONCLUSIONS: The model elaborated showed good performance, even when data from patients scanned on 1.5 T and 3 T were merged. This shows that magnetic field intensity variability can be overcome by means of selecting appropriate image features.

Patient-Reported Work Ability During the First Two Years After Rectal Cancer Diagnosis.

BACKGROUND: Rectal cancer treatment is associated with substantial short- and longer-term morbidity that may affect patients' ability to work. OBJECTIVE: We evaluated patient-reported work ability during the first 2 years after rectal cancer diagnosis, relative to the Dutch general population. Also, we assessed the association between clinical factors and work ability. DESIGN: This is a prospective cohort study. SETTINGS: This study was conducted at the Radiation-Oncology Department of a tertiary center. PATIENTS: Patients with rectal cancer, <67 years of age, and treated with curative intent were selected. MAIN OUTCOME MEASURES: Work ability was assessed with the Work Ability Index before the start of treatment (baseline) and at 3, 6, 12, 18, and 24 months after. The Work Ability Index scores of patients with paid employment were compared with the scores of matched population controls. Mixed models were used to estimate the impact of clinical factors on work ability. RESULTS: Of the 230 eligible patients, 172 (75%) had paid employment. Work ability decreased at 3 and 6 months compared with baseline. At 12 months, work ability recovered to baseline level but remained significantly lower than in population controls up to 24 months. Fifty-four percent reported 100 to 365 days of sick leave during the first 12 months of treatment versus 2% in the general population. At 24 months, 32% needed substantial adaptations in work activities, worked reduced hours, or were unable to work due to the disease versus 6% in the general population. Female sex, multiple comorbidities, oligometastatic disease, chemoradiation, and abdominoperineal resection were associated with lower work ability. LIMITATIONS: The study was limited by a decrease in questionnaire response rate from 83% to 64% over time. CONCLUSIONS: Patient-reported work ability deteriorates during rectal cancer treatment. Within 24 months after diagnosis, work ability returns to pretreatment level but remains lower than that of the general population. See Video Abstract at http://links.lww.com/DCR/B175. CAPACIDAD DE TRABAJO REPORTADO POR PACIENTES DURANTE LOS PRIMEROS DOS AÑOS DESPUÉS DEL DIAGNÓSTICO DE CÁNCER RECTAL: El tratamiento del cáncer rectal se asocia con una morbilidad significante a corto y largo plazo que puede afectar la capacidad de trabajo de pacientes.Evaluamos la capacidad de trabajo reportado por pacientes durante los primeros dos años después del diagnóstico de cáncer rectal, en relación con la población general holandesa. Además, evaluamos la asociación entre los factores clínicos y capacidad para trabajar.Estudio de cohorte prospectivo.Este estudio se realizó en el Departamento de Radiación Oncológica de en un centro de referencia de tercer nivel.Se seleccionaron pacientes con cáncer rectal, <67 años de edad, y tratados con intención curativa.La capacidad de trabajo se evaluó con el índice de capacidad de trabajo antes del inicio del tratamiento (línea de base) y a los 3, 6, 12, 18 y 24 meses después. Los puntajes de capacidad laboral de los pacientes con empleo remunerado se compararon con los puntajes de los controles de población pareados. Se utilizaron modelos mixtos para estimar el impacto de los factores clínicos en la capacidad laboral.De los 230 pacientes elegibles, 172 (75%) tenían empleo remunerado. La capacidad de trabajo disminuyó a los 3 y 6 meses en comparación con la línea de base. A los 12 meses, la capacidad de trabajo se recuperó al nivel de referencia, pero se mantuvo significativamente más baja que en los controles de la población hasta 24 meses. Durante los primeros 12 meses, el 54% reportó 100-365 días de baja por enfermedad versus el 2% en la población general. A los 24 meses, el 32% necesitaba adaptaciones sustanciales en las actividades laborales, trabajó horas reducidas o no pudo trabajar debido a la enfermedad frente al 6% en la población general. El sexo femenino, las comorbilidades múltiples, la enfermedad oligometastásica, la quimiorradiación y la resección abdominoperineal se asociaron con una menor capacidad de trabajo.El estudio estuvo limitado por una disminución en la tasa de respuesta al cuestionario del 83% al 64% a lo largo plazo.La capacidad laboral informada por el paciente se deteriora durante el tratamiento del cáncer rectal. Dentro de los 24 meses posteriores al diagnóstico, la capacidad laboral vuelve al nivel de pretratamiento, pero sigue siendo inferior a la de la población general. Consulte Video Resumen en http://links.lww.com/DCR/B175. (Traducción-Dr. Adrian Ortega).

MRI-based tumor inter-fraction motion statistics for rectal cancer boost radiotherapy.

BACKGROUND: In patients diagnosed with rectal cancer, dose escalation is currently being investigated in a large number of studies. Since there is little known on gross tumor volume (GTV) inter-fraction motion for rectal cancer, a wide variety in margins is used. Purpose of this study is to quantify GTV inter-fraction motion statistics on different timescales and to give estimates of planning target volume (PTV) margins. MATERIAL AND METHODS: Thirty-two patients, diagnosed with rectal cancer, were included. To investigate motion from week-to-week, 16 patients underwent a pretreatment and five weekly MRIs, prior to a radiotherapy (RT) fraction of the chemoradiotherapy treatment. To investigate motion from day-to-day, the remaining 16 patients underwent five daily MRIs before each fraction in one week of RT. GTV was delineated on all scans according to guidelines. Scans were aligned on bony anatomy with the first MRI. For both datasets separately, GTV inter-fraction motion was determined based on center-of-gravity displacement. Therefrom, systematic and random errors were determined in left/right (LR), anterior/posterior and cranial/caudal (CC) direction. PTV margin estimates were calculated and evaluated on GTV coverage. RESULTS: Systematic and random errors were found in the range of 2.3-4.8 mm and 1.5-3.3 mm from week-to-week, and 1.8-4.5 mm and 1.8-4.0 mm from day-to-day, respectively. On both timescales, similar motion patterns were found; the most motion was observed in CC whilst the least motion was observed in LR. On the week-to-week data more systematic and less random motion was observed compared to the day-to-day data. Overall, only slight differences in margin estimates were found. Derived PTV margin estimates were found to give adequate GTV coverage. CONCLUSION: GTV inter-fraction motion, on a week-to-week and day-to-day timescale, can be accounted for using motion statistics presented in this study.

Health-related quality of life in rectal cancer patients undergoing neoadjuvant chemoradiation with delayed surgery versus short-course radiotherapy with immediate surgery: a propensity score-matched cohort study.

BACKGROUND: Neoadjuvant chemoradiation with delayed surgery (CRT-DS) and short-course radiotherapy with immediate surgery (SCRT-IS) are two commonly used treatment strategies for rectal cancer. However, the optimal treatment strategy for patients with intermediate-risk rectal cancer remains a discussion. This study compares quality of life (QOL) between SCRT-IS and CRT-DS from diagnosis until 24 months after treatment. METHODS: In a prospective colorectal cancer cohort, rectal cancer patients with clinical stage T2-3N0-2M0 undergoing SCRT-IS or CRT-DS between 2013 and 2017 were identified. QOL was assessed using EORTC-C30 and EORTC-CR29 questionnaires before the start of neoadjuvant treatment (baseline) and at 3, 6, 12, 18 and 24 months after. Patients were 1:1 matched using propensity sore matching. Between- and within-group differences in QOL domains were analyzed with linear mixed-effects models. Symptoms and sexual interest at 12 and 24 months were compared using logistic regression models. RESULTS: 156 of 225 patients (69%) remained after matching. The CRT-DS group reported poorer emotional functioning at 3, 6, 12, 18 and 24 months (mean difference with SCRT-IS: -9.4, -12.1, -7.3, -8.0 and -7.9 respectively), and poorer global health, physical-, role-, social- and cognitive functioning at 6 months (mean difference with SCRT-IS: -9.1, -9.8, -14.0, -9.2 and -12.6, respectively). Besides emotional functioning, all QOL domains were comparable at 12, 18 and 24 months. Within-group changes showed a significant improvement of emotional functioning after baseline in the SCRT-IS group, whereas only a minor improvement was observed in the CRT-DS group. Symptoms and sexual interest in male patients at 12 and 24 months were comparable between the groups. CONCLUSIONS: In rectal cancer patients, CRT-DS may induce a stronger decline in short-term QOL than SCRT-IS. From 12 months onwards, QOL domains, symptoms and sexual interest in male patients were comparable between the groups. However, emotional functioning remained higher after SCRT-IS than after CRT-DS.

Utility Scores and Preferences for Surgical and Organ-Sparing Approaches for Treatment of Intermediate and High-Risk Rectal Cancer.

BACKGROUND: Organ-sparing approaches, including wait-and-see and local excision, are increasingly being offered to patients with rectal cancer following a good response to neoadjuvant therapy. Preferences regarding these treatment strategies are yet unknown. OBJECTIVE: This study aimed to determine the preferences and utility scores for rectal cancer treatment approaches. DESIGN: This is a cross-sectional study. SETTING: This study was conducted at the Radiation-Oncology Department of the University Medical Center Utrecht. PATIENTS: Fifty-seven patients with a history of rectal cancer and 38 volunteers were included. MAIN OUTCOME MEASURES: Participants assessed 6 hypothetical treatment-outcome scenarios, including short-course radiotherapy or chemoradiation followed by abdominoperineal resection, low anterior resection, local excision, or a wait-and-see approach. The hierarchy in preferences between scenarios was assessed by using ranking. Utilities were estimated with a visual analog scale and time trade-off. RESULTS: Organ-sparing approaches were ranked as the first preferred treatment option by 51% of the participants. Among all scenarios, wait-and-see was most often ranked highest by patients and volunteers (36% and 50%). Meanwhile, a substantial proportion ranked wait-and-see as their lowest preference (38% in patients and 35% in volunteers). Utility scores differed significantly between scenarios. Wait-and-see received a significantly higher score on the visual analog scale than the scenarios including abdominoperineal resection and the scenario including chemoradiation with low anterior resection, and a score similar to the scenarios including local excision and short-course radiotherapy with low anterior resection. LIMITATIONS: The study population consisted of patients with a history of rectal cancer treatment and volunteers related to patients. This may have influenced preferences. CONCLUSIONS: This study suggests that there is a wide disparity in preferences concerning organ-sparing approaches for rectal cancer in both patients with a history of rectal cancer and volunteers. Wait-and-see is often the highest preferred treatment, but it is also among the least preferred treatment options. These findings give insights into how patients may value the current rectal cancer treatment options. See Video Abstract at http://links.lww.com/DCR/A521.

Tumor volume regression during preoperative chemoradiotherapy for rectal cancer: a prospective observational study with weekly MRI.

PURPOSE: Few data is available on rectal tumor shrinkage during preoperative chemoradiotherapy (CRT). This regression pattern is interesting to optimize timing of dose escalation on the tumor. METHODS: Gross tumor volumes (GTV) were contoured by two observers on magnetic resonance imaging (MRI) obtained before, weekly during, 2-4 weeks after, and 7-8 weeks after a 5-week course of concomitant CRT for rectal cancer. RESULTS: Overall, 120 MRIs were acquired in 15 patients. A statistically significant tumor volume reduction is seen from the first week, and between any two time points (p < .007). At the end of CRT, 46.3% of the initial tumor volume remained, and 32.4% at time of surgery. PTV measured 61.2% at the end of treatment. Tumor shrinkage is the fastest in the beginning of treatment (26%/week), slows down to 7%/week in the last 2 weeks of CRT, and finally to 1.3%/week in the last 5 weeks before surgery. CONCLUSIONS: The main rectal tumor regression occurs during CRT course itself, and mostly in the first half, with shrinking speed decreasing over the course. This suggests that a sequential boost is preferably done after the elective fields, yielding an average PTV-reduction of 39%. A simultaneous integrated boost strategy could benefit from adaptive planning during the course.

Systematic review on the role of serum tumor markers in the detection of recurrent pancreatic cancer.

BACKGROUND: Biomarker testing can be helpful to monitor disease progression after resection of pancreatic cancer. This systematic review aims to give an overview of the literature on the diagnostic value of serum tumor markers for the detection of recurrent pancreatic cancer during follow-up. METHODS: A systematic search was performed to 2 October 2017. All studies reporting on the diagnostic value of postoperatively measured serum biomarkers for the detection of pancreatic cancer recurrence were included. Data on diagnostic accuracy of tumor markers were extracted. Forest plots and pooled values of sensitivity and specificity were calculated. RESULTS: Four articles described test results of CA 19-9. A pooled sensitivity and specificity of respectively 0.73 (95% CI 0.66-0.80) and 0.83 (95% CI 0.73-0.91) were calculated. One article reported on CEA, showing a sensitivity of 50% and specificity of 65%. No other serum tumor markers were discussed for surveillance purposes in the current literature. CONCLUSION: Although testing of serum CA 19-9 has considerable limitations, CA 19-9 remains the most used serum tumor marker for surveillance after surgical resection of pancreatic cancer. Further studies are needed to assess the role of serum tumor marker testing in the detection of recurrent pancreatic cancer and to optimize surveillance strategies.

Systematic review on the impact of pancreatoduodenectomy on quality of life in patients with pancreatic cancer.

BACKGROUND: Patients undergoing pancreatoduodenectomy for pancreatic cancer have a high risk of major postoperative complications and a low survival rate. Insight in the impact of pancreatoduodenectomy on quality of life (QoL) is therefore of great importance. The aim of this systematic review was to assess QoL after pancreatoduodenectomy for pancreatic cancer. METHODS: A systematic review of the literature was performed according to the PRISMA guidelines. A systematic search of all the English literature available in PubMed and Medline was performed. All studies assessing QoL with validated questionnaires in pancreatic cancer patients undergoing pancreatoduodenectomy were included. RESULTS: After screening a total of 788 articles, the full texts of 36 articles were assessed, and 17 articles were included. QoL of physical and social functioning domains decreased in the first 3 months after surgery. Recovery of physical and social functioning towards baseline values took place after 3-6 months. Pain, fatigue and diarrhoea scores deteriorated postoperatively, but eventually resolved after 3-6 months. CONCLUSION: Pancreatoduodenectomy for malignant disease negatively influences QoL in the physical and social domains at short term. It will eventually recover to baseline values after 3-6 months. This information is valuable for counselling and expectation management of patients undergoing pancreatoduodenectomy.

Long-term health-related quality of life after pancreatic resection for malignancy in patients with and without severe postoperative complications.

BACKGROUND: Surgery for pancreatic cancer yields significant morbidity and mortality risks and survival is limited. Therefore, the influence of complications on quality of life (QoL) after pancreatic surgery is important. This study compares QoL in patients with and without severe complications after surgery for pancreatic (pre-)malignancy. METHODS: This prospective cohort study scored complications after pancreatic surgery according to the Clavien-Dindo system and the definitions of the International Study Group of Pancreatic Surgery. QoL was measured by the RAND36 questionnaire, the European Organization for Research and Treatment of Cancer core questionnaire (QLQ-C30) and the pancreas specific QLQ-PAN26. QoL in patients with severe complications was compared with QoL in patients with no or mild complications over a period of 12 months. Analysis was performed with linear mixed models for repeated measurements. RESULTS: Between March 2012 and July 2016, 137 patients were included. Sixty-eight patients (50%) had at least 1 severe complication. There were no statistically significant and clinically relevant differences between both groups in QoL up to 12 months after surgery. CONCLUSION: In this study, no differences in QoL between patients with and without severe postoperative complications were encountered during the first 12 months after surgery for pancreatic (pre-)malignancy. TRIAL REGISTRATION: http://www.clinicaltrials.gov Identifier: NCT02175992.