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.

Changes in breast cancer treatment during the COVID-19 pandemic: a Dutch population-based study.

PURPOSE: We aimed to compare (1) treatments and time intervals between treatments of breast cancer patients diagnosed during and before the COVID-19 pandemic, and (2) the number of treatments started during and before the pandemic. METHODS: Women were selected from the Netherlands Cancer Registry. For aim one, odds ratios (OR) and 95% confidence intervals (95%CI) were calculated to compare the treatment of women diagnosed within four periods of 2020: pre-COVID (weeks 1-8), transition (weeks 9-12), lockdown (weeks 13-17), and care restart (weeks 18-26), with data from 2018/2019 as reference. Wilcoxon rank-sums test was used to compare treatment intervals, using a two-sided p-value < 0.05. For aim two, number of treatments started per week in 2020 was compared with 2018/2019. RESULTS: We selected 34,097 women for aim one. Compared to 2018/2019, neo-adjuvant chemotherapy was less likely for stage I (OR 0.24, 95%CI 0.11-0.53), stage II (OR 0.63, 95%CI 0.47-0.86), and hormone receptor+/HER2- tumors (OR 0.55, 95%CI 0.41-0.75) diagnosed during transition. Time between diagnosis and first treatment decreased for patients diagnosed during lockdown with a stage I (p < 0.01), II (p < 0.01) or III tumor (p = 0.01). We selected 30,002 women for aim two. The number of neo-adjuvant endocrine therapies and surgeries starting in week 14, 2020, increased by 339% and 18%, respectively. The number of adjuvant chemotherapies decreased by 42% in week 15 and increased by 44% in week 22. CONCLUSION: The pandemic and subsequently altered treatment recommendations affected multiple aspects of the breast cancer treatment strategy and the number of treatments started per week.

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.

Work Ability in Patients With Stage I to IV Colon Cancer: Results of the Dutch Prospective Colorectal Cancer Cohort.

BACKGROUND: Colon cancer affects a patient's ability to work. Many patients who have colon cancer are employed at the time of diagnosis. OBJECTIVE: We evaluated work ability during the first 2 years after colon cancer diagnosis. DESIGN: This study is a national prospective study, the Prospective Dutch ColoRectal Cancer cohort, including clinical data and patient-reported outcomes. SETTINGS: Data were collected in 59 medical centers in the Netherlands. PATIENTS: Patients <67 years of age with stage I to IV colon cancer and who completed Work Ability Index questionnaires were selected. MAIN OUTCOME MEASURES: Work ability was assessed at baseline, 3, 6, 12, 18, and 24 months. The Work Ability Index (range, 0 to 49) was evaluated using linear mixed models. Outcomes were matched to population controls without cancer. RESULTS: Of 390 patients, 84% had paid employment. Work ability of patients with stage I to IV colon cancer was significantly lower at the time of diagnosis than in matched population controls (31 ± 8.2 and 41 ± 5.6). Patients with stage I to III disease receiving surgery only regained Work Ability Index scores comparable to matched population controls at 18 months. Patients receiving adjuvant systemic treatment initially demonstrated a decrease in work ability with improvements from 6 months onward and normalization at 24 months. Patients with stage IV disease did not demonstrate improvements in work ability outcomes over time. Work ability scores were negatively influenced by the administration of systemic treatment and ≥1 comorbidities. LIMITATIONS: Only patients with patient-reported outcomes and work at baseline were included in this analysis. Also, questionnaire response rates decreased over time. CONCLUSIONS: Work ability in patients with colon cancer is decreased for a prolonged time. Recovery depends on disease stage, type of treatment, and comorbidities. Patients with stage I to III disease treated with curative surgery alone were the first to regain work ability, followed by patients who receive adjuvant chemotherapy. Patients with stage IV disease did not regain work ability. See Video Abstract at http://links.lww.com/DCR/B759 . CAPACIDAD LABORAL EN PACIENTES CON CNCER DE COLON EN ESTADIO IIV RESULTADOS PROSPECTIVOS DE CNCER COLORECTAL EN UNA COHORTE HOLANDESA: ANTECEDENTES:El cáncer de colon afecta la capacidad de trabajo en un paciente. Muchos pacientes con cáncer de colon están empleados en el momento del diagnóstico.OBJETIVO:Evaluamos la capacidad laboral durante los dos primeros años posteriores al diagnóstico de cáncer de colon.DISEÑO:Es un estudio prospectivo nacional, la cohorte de cáncer colorrectal holandés, incluye datos clínicos y resultados informados por los pacientes.ENTORNO CLINICO:Se recopilaron datos de 59 centros médicos en los Países Bajos.PACIENTES:Se seleccionaron pacientes < 67 años, con cáncer de colon en estadio I-IV, que completaron los cuestionarios de índice de capacidad para el trabajo.PRINCIPALES MEDIDAS DE VALORACIÓN:La capacidad para el trabajo se evaluó al inicio, a los 3, 6, 12, 18 y 24 meses. El índice de capacidad para el trabajo (que va de 0 a 49) se evaluó mediante modelos lineales mixtos. Los resultados fueron comparados con el grupo control sin cáncer.RESULTADOS:De 390 pacientes, el 84% tenía un empleo remunerado. La capacidad de trabajo de los pacientes en estadio I-IV fue significativamente menor en el momento del diagnóstico en comparación con el grupo control (31 ± 8,2 y 41 ± 5,6, respectivamente). Los pacientes con enfermedad en estadio I-III que recibieron cirugía lograron recuperar puntajes del índice de capacidad laboral comparables a los controles a los 18 meses. Los pacientes que recibieron tratamiento sistémico adyuvante inicialmente demostraron una disminución en la capacidad de trabajo con mejoras a partir de los 6 meses en adelante y una normalización a los 24 meses. Los pacientes en estadio IV no demostraron mejoras en los resultados de la capacidad laboral a lo largo del tiempo. Las puntuaciones de capacidad para el trabajo se vieron influidas negativamente por la administración del tratamiento sistémico y la existencia de ≥1 comorbilidades.LIMITACIONES:En este análisis solo se incluyeron los pacientes con resultados y trabajo desde el inicio del estudio. Además, las tasas de respuesta al cuestionario disminuyeron con el tiempo.CONCLUSIONES:La capacidad de trabajo en pacientes con cáncer de colon se reduce durante un tiempo prolongado. La recuperación depende del estadio de la enfermedad, el tipo de tratamiento y la comorbilidad. Los pacientes con enfermedad en estadio I-III tratados con cirugía curativa exclusivamente, son los primeros en recuperar la capacidad para trabajar, seguidos de los pacientes que reciben quimioterapia adyuvante. Los pacientes con enfermedad en estadio IV no recuperan la capacidad para trabajar. Consulte Video Resumen en http://links.lww.com/DCR/B759 . (Traducción- Dr. Ingrid Melo ).

Patient Expectations About Palliative Treatment for Symptomatic Spinal Metastases: A Qualitative Study.

OBJECTIVES: Patients with spinal metastases often receive palliative surgery or radiation therapy to maintain or improve health-related quality of life. Patients with unrealistic expectations regarding treatment outcomes have been shown to be less satisfied with their post-treatment health status. This study evaluated expectations of patients with spinal metastases scheduled for surgery and/or radiation therapy. METHODS: Individual semistructured interviews were conducted with patients with symptomatic spinal metastases before and 6 weeks after surgery and/or radiation therapy. Expectations regarding treatment outcomes were discussed before treatment, and level of fulfillment of these pretreatment expectations was discussed after treatment. Interviews were recorded, transcribed and analyzed according to the thematic analysis method to identify themes. RESULTS: Before treatment, patients thought they were not, or minimally, informed about (expected) treatment outcomes, but they felt well informed about treatment procedures and possible complications. Although patients expected pain relief and improvement in daily functioning, they found it difficult to describe any recovery timeline or the impact of these expected improvements on their daily life. Patients generally understood that treatment was not curative, but lacked insight into the impact of treatment on life expectancy given that this was hardly discussed by their surgeon and/or radiation oncologist. Pretreatment expectations regarding pain and daily functioning were only partially met in most patients post-treatment. CONCLUSIONS: Patients thought they were not, or only minimally, informed about expected outcomes after surgery and/or radiation therapy for symptomatic spinal metastases. Improvements in patient-physician communication and counseling could help guide patients toward realistic pretreatment expectations.

Feasibility and first results of the 'Trials-within-Cohorts' (TwiCs) design in patients undergoing radiotherapy for lung cancer.

Background: 'Trials-within-Cohorts' (TwiCs), previously known as 'cohort multiple randomized controlled trials' is a pragmatic trial design, supporting an efficient and representative recruitment of patients for (future) trials. To our knowledge, the 'COhort for Lung cancer Outcome Reporting and trial inclusion' (COLOR) is the first TwiCs in lung cancer patients. In this study we aimed to assess the feasibility and first year results of COLOR.Material and Methods: All patients diagnosed with lung cancer referred to the Radiotherapy department were eligible to participate in the ongoing prospective COLOR study. At inclusion, written informed consent was requested for use of patient data, participation in patient-reported outcomes (PROs), and willingness to participate in (future) trials. Feasibility was studied by assessing participation and comparing baseline PROs to EORTC reference values. First-year results of PROs at baseline and 3 months after inclusion were evaluated separately for stereotactic body radiotherapy (SBRT) and conventional radiotherapy patients.Results: Of the 338 eligible patients between July 2020 and July 2021, 169 (50%) participated. Among these, 127 (75%) gave informed consent to PROs participation and 110 (65%) were willing to participate in (future) trials. The inclusion percentage dropped from 77% to 33% when the information procedure was switched from in-person to by phone (due to COVID-19 pandemic measures). Baseline PROs for physical and cognitive functioning were comparable in COLOR patients compared to the EORTC reference values. No significant changes in PROs were observed 3 months after inclusion, except for a slight increase in pain scores in the SBRT group (n = 97).Conclusions: The TwiCs-design appears feasible in lung cancer patients with fair participation rates (although negatively impacted by the COVID-19 pandemic). With a planned expansion to other centers, the COLOR-study is expected to enable multiple (randomized) evaluations of experimental interventions with important advantages for recruitment, generalizability, and long-term outcome data collection.

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.

Breast cancer patients' needs and perspectives on a one-on-one peer support program: quantitative and qualitative analyses.

PURPOSE: Although peer support programs as a health resource have become increasingly popular, only limited studies evaluated the added value of one-on-one peer support for breast cancer patients. This study aims to bridge the knowledge gap by focusing on two related research topics. First, we evaluated emotional well-being and (unmet) needs regarding supportive care. Second, we evaluated patients' perspectives on their experiences after having one-on-one peer support. METHODS: A quantitative analysis was conducted to provide insight in patients' symptoms of anxiety and depression (HADS), quality of life (EORTC-QLQ-C30), and supportive care needs (CaSUN-questionnaire). Furthermore, approximately 1 year after the implementation of a one-on-one peer support program, focus groups were conducted to evaluate patients' perspectives regarding one-on-one peer support. RESULTS: Two hundred twenty-five of 537 patients diagnosed with breast cancer between 2019 and 2020 completed the questionnaires. Quantitative analysis showed increased symptoms of anxiety and depression among breast cancer patients and lower scores on all EORTC-QLQ-C30 domains compared to the Dutch normative population. Of all patients, 27.6% (95%CI = 0.22-0.34) reported to have unmet needs regarding emotional support and 23.1% (95%CI = 0.18-0.29) reported an unmet need to talk to someone who has experienced breast cancer. For the qualitative analysis, 19 breast cancer patients who were taking part in the one-on-one peer support program participated in three focus groups. Benefits, limitations, and wishes regarding the one-on-one peer support program were discussed. CONCLUSION: Breast cancer patients showed increased anxiety and depression and lower quality of life, physical, role, emotional, cognitive, and social functioning compared to the Dutch normative population. Almost one-third of breast cancer patients reported unmet needs regarding emotional support and a desire to talk to other breast cancer patients. These (unmet) needs can successfully be met by providing a low-threshold one-on-one peer support program.

Physical and mental health of breast cancer patients and survivors before and during successive SARS-CoV-2-infection waves.

PURPOSE: During the first SARS-CoV-2-infection wave, a deterioration in emotional well-being and increased need for mental health care were observed among patients treated or being treated for breast cancer. In this follow-up study, we assessed patient-reported quality of life (QoL), physical functioning, and psychosocial well-being during the second SARS-CoV-2-infection wave in a large, representative cohort. METHODS: This longitudinal cohort study was conducted within the prospective, multicenter UMBRELLA breast cancer cohort. To assess patient-reported QoL, physical functioning and psychosocial well-being, COVID-19-specific surveys were completed by patients during the first and second SARS-CoV-2-infection waves (April and November 2020, respectively). An identical survey was completed by a comparable reference population during the second SARS-CoV-2-infection waves. All surveys included the validated EORTC-QLQ-C30/BR23, HADS and "De Jong-Gierveld Loneliness" questionnaires. Pre-COVID-19 EORTC-QLQ-C30/BR23 and HADS outcomes were available from UMBRELLA. Response rates were 69.3% (n = 1106/1595) during the first SARS-CoV-2-infection wave and 50.9% (n = 822/1614) during the second wave. A total of 696 patients responded during both SARS-CoV-2-infection waves and were included in the analysis comparing patient-reported outcomes (PROs) during the second SARS-CoV-2-infection wave to PROs during the first wave. Moreover, PROs reported by all patients during the second SARS-CoV-2-infection wave (n = 822) were compared to PROs of a similar non-cancer reference population (n = 241) and to their pre-COVID-19 PROs. RESULTS: Patient-reported QoL, physical functioning, and psychosocial well-being of patients treated or being treated for breast cancer remained stable or improved from the first to the second SARS-CoV-2-infection wave. The proportion of emotional loneliness reduced from 37.6 to 29.9% of patients. Compared to a similar non-cancer reference population, physical, emotional, and cognitive functioning, future perspectives and symptoms of dyspnea and insomnia were worse in patients treated or being treated for breast cancer during the second SARS-CoV-2-infection wave. PROs in the second wave were similar to pre-COVID-19 PROs. CONCLUSION: Although patients scored overall worse than individuals without breast cancer, QoL, physical functioning, and psychosocial well-being did not deteriorate between the first and second wave. During the second wave, PROs were similar to pre-COVID-19 values. Overall, current findings are cautiously reassuring for future mental health of patients treated or being treated for breast cancer.

Translation of IDEA trial results into clinical practice: Analysis of the implementation of a new guideline for colon cancer.

The IDEA trial showed no clinical relevant differences in efficacy between 3 and 6 months of oxaliplatin-based adjuvant chemotherapy (ACT) in colon cancer (CC), while toxicity was substantially lower in the 3 months regimen. Therefore, in 2017 the Dutch colorectal cancer guideline was revised and currently recommends 3 months of oxaliplatin-based ACT. Furthermore, the definition of high-risk stage II CC was restricted to pT4 tumors. We analyzed changes in ACT between 2015 and 2019. From the Netherlands Cancer Registry all 16 721 patients ≥18 years with resected high-risk stage II and stage III CC during 2015 to 2019 were selected. Differences in patient and treatment characteristics were analyzed per calendar year according to stage and age. Mean duration of oxaliplatin-based ACT decreased from 18.6 (±8.0) to 9.5 (±3.8) weeks between 2015 and 2019. In patients receiving ACT (n = 8170), the proportion treated with oxaliplatin increased from 74% to 83%. The proportion of patients receiving ACT was stable, 61% to 69% in stage III and 26% to 29% in pT4 stage II. ACT in previous high-risk pT3N0 disease decreased from 15% to 3%. Use of oxaliplatin increased from 27% to 49% in patients aged ≥75 years. The revised guideline was rapidly implemented and led to an increase in oxaliplatin-based ACT in the elderly and increased guideline-adherence in high-risk stage II CC.

Breast cancer recurrence after immediate and delayed postmastectomy breast reconstruction-A systematic review and meta-analysis.

BACKGROUND: Oncological safety of different types and timings of PMBR after breast cancer remains controversial. Lack of stratified risk assessment in literature makes current clinical and shared decision-making complex. This is the first systematic review and meta-analysis to evaluate differences in oncological outcomes after immediate versus delayed postmastectomy breast reconstruction (PMBR) for autologous and implant-based PMBR separately. METHODS: A systematic literature search was performed in MEDLINE, Cochrane Library, and Embase. The Cochrane Collaboration Handbook and Meta-analysis Of Observational Studies in Epidemiology checklist were followed for data abstraction. Variability in point estimates attributable to heterogeneity was assessed using I2 -statistic. (Loco)regional breast cancer recurrence rates, distant metastasis rates, and overall breast cancer recurrence rates were pooled in generalized linear mixed models using random effects. RESULTS: Fifty-five studies, evaluating 14,217 patients, were included. When comparing immediate versus delayed autologous PMBR, weighted average proportions were: 0.03 (95% confidence interval [CI], 0.02-0.03) versus 0.02 (95% CI, 0.01-0.04), respectively, for local recurrences, 0.02 (95% CI, 0.01-0.03) versus 0.02 (95% CI, 0.01-0.03) for regional recurrences, and 0.04 (95% CI, 0.03-0.06) versus 0.01 (95% CI, 0.00-0.03) for locoregional recurrences. No statistically significant differences in weighted average proportions for local, regional and locoregional recurrence rates were observed between immediate and delayed autologous PMBR. Data did not allow comparing weighted average proportions of distant metastases and total breast cancer recurrences after autologous PMBR, and of all outcome measures after implant-based PMBR. CONCLUSIONS: Delayed autologous PMBR leads to similar (loco)regional breast cancer recurrence rates compared to immediate autologous PMBR. This study highlights the paucity of strong evidence on breast cancer recurrence after specific types and timings of PMBR. LAY SUMMERY: Oncologic safety of different types and timings of postmastectomy breast reconstruction (PMBR) remains controversial. Lack of stratified risk assessment in literature makes clinical and shared decision-making complex. This meta-analysis showed that delayed autologous PMBR leads to similar (loco)regional recurrence rates as immediate autologous PMBR. Data did not allow comparing weighted average proportions of distant metastases and total breast cancer recurrence after autologous PMBR, and of all outcome measures after implant-based PMBR. Based on current evidence, oncological concerns do not seem a valid reason to withhold patients from certain reconstructive timings or techniques, and patients should equally be offered all reconstructive options they technically qualify for.

Sentinel Lymph Node Mapping in Breast Cancer Patients Through Fluorescent Imaging Using Indocyanine Green: The INFLUENCE Trial.

OBJECTIVE: The aim was to compare the (sentinel) lymph node detection rate of indocyanine green (ICG)-fluorescent imaging versus standard-of-care 99m Tc-nanocoilloid for sentinel lymph node (SLN)-mapping. BACKGROUND: The current gold standard for axillary staging in patients with breast cancer is sentinel lymph node biopsy (SLNB) using radio-guided surgery using radioisotope technetium ( 99m Tc), sometimes combined with blue dye. A promising alternative is fluorescent imaging using ICG. METHODS: In this noninferiority trial, we enrolled 102 consecutive patients with invasive early-stage, clinically node-negative breast cancer. Patients were planned for breast conserving surgery and SLNB between August 2020 and June 2021. The day or morning before surgery, patients were injected with 99m Tc-nanocolloid. In each patient, SLNB was first performed using ICG-fluorescent imaging, after which excised lymph nodes were tested with the gamma-probe for 99m Tc-uptake ex vivo, and the axilla was checked for residual 99m Tc-activity. The detection rate was defined as the proportion of patients in whom at least 1 (S)LN was detected with either tracer. RESULTS: In total, 103 SLNBs were analyzed. The detection rate of ICG-fluorescence was 96.1% [95% confidence interval (95% CI)=90.4%-98.9%] versus 86.4% (95% CI=78.3%-92.4%) for 99m Tc-nanocoilloid. The detection rate for pathological lymph nodes was 86.7% (95% CI=59.5%-98.3%) for both ICG and 99m Tc-nanocoilloid. A median of 2 lymph nodes were removed. ICG-fluorescent imaging did not increase detection time. No adverse events were observed. CONCLUSIONS: ICG-fluorescence showed a higher (S)LN detection rate than 99m Tc-nanocoilloid, and equal detection rate for pathological (S)LNs. ICG-fluorescence may be used as a safe and effective alternative to 99m Tc-nanocoilloid for SLNB in patients with early-stage breast cancer.

Alternative Randomized Trial Designs in Surgery: A Systematic Review.

INTRODUCTION: Randomized controlled trials (RCTs) yield the highest level of evidence but are notoriously difficult to perform in surgery. Surgical RCTs may be hampered by slow accrual, the surgical learning curve, and lack of financial support. Alternative RCT designs such as stepped-wedge randomized controlled trials (SW-RCTs), registry-based randomized controlled trials (RB-RCTs), and trials-within-cohorts (TwiCs) may overcome several of these difficulties. This review provides an overview of alternative RCT designs used in surgical research. METHODS: We systematically searched PubMed, EMBASE, and Cochrane Central for surgical SW-RCTs, RB-RCTs, and TwiCs. A surgical RCT was defined as a randomized trial that studied interventions in patients undergoing general surgery, regardless of the affiliation of the corresponding author. Exponential regression analysis was performed to assess time trends. RESULTS: Overall, 41 surgical RCTs using alternative designs were identified, including 17 published final RCT reports and 24 published protocols of ongoing RCTs. These included 25 SW-RCTs (61%), 13 RB-RCTs (32%), and 3 TwiCs (7%). Most of these RCTs were performed in Europe (63%) and within gastrointestinal/oncological surgery (41%). The total number of RCTs using alternative designs exponentially increased over the last 7 years ( P <0.01), with 95% (n=39/41) of the total number published within this time frame. The most reported reasons for using alternative RCT designs were avoidance of contamination for SW-RCTs and generalizability of the trial population for RB-RCTs and TwiCs. CONCLUSIONS: Alternative RCT designs are increasingly used in surgical research, mostly in Europe and within gastrointestinal/oncological surgery. When adequately used, these alternative designs may overcome several difficulties associated with surgical RCTs.

External Validity of the Multicenter Randomized PREOPANC Trial on Neoadjuvant Chemoradiotherapy in Pancreatic Cancer: Outcome of Eligible but Nonrandomized Patients.

OBJECTIVES: To investigate the accrual proportion and patients' reasons for not participating in the PREOPANC trial on neoadjuvant chemoradiotherapy versus immediate surgery in resectable and borderline resectable pancreatic cancer, and to compare these patients' outcomes with those of patients who had been randomized in the trial. SUMMARY OF BACKGROUND DATA: The external validity of multicenter randomized trials in cancer treatment has been criticized for suboptimal non-representative inclusion. In trials, it is unclear how outcomes compare between randomized and nonrandomized patients. METHODS: At 8 of 16 participant centers, this multicenter observational study identified validation patients, who had been eligible but not randomized during recruitment for the PREOPANC trial. We assessed the accrual proportion, investigated their most common reasons for not participating in the trial, and compared resection rates, radical (R0) resection rates, and overall survival between the validation patients and PREOPANC patients, who had been randomized in the trial to immediate surgery. RESULTS: In total, 455 patients had been eligible during the recruitment period, 151 of whom (33%) had been randomized. Fifty-five percent of the 304 validation patients had refused to participate. Median overall survival in the validation group was 15.2 months, against 15.5 months in the PREOPANC group (P = 1.00). The respective resection rates (76% vs 73%) and R0 resection rates (51% vs 46%) did not differ between the groups. CONCLUSIONS: The PREOPANC trial included a reasonable percentage of 33% of eligible patients. In terms of the outcomes survival, resection rate, and R0 resection rate, this appeared to be a representative group.

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.

The impact of the COVID-19 pandemic on perceived access to health care and preferences for health care provision in individuals (being) treated for breast cancer.

PURPOSE: To evaluate perceived access to health care and preferences for health care provision among patients (being) treated for breast cancer during the COVID-19 pandemic. METHODS: Longitudinal study within the prospective, multicenter UMBRELLA cohort of patients (being) treated for breast cancer. All cohort participants enrolled in UMBRELLA between October 2013 and November 2020 were sent a COVID-19-specific survey during the first and second wave of the COVID-19 pandemic, i.e., April 2020 and November 2020, respectively. RESULTS: In total, 1106 (69.3%) and 822 (50.9%) cohort participants completed the survey in the first and second wave, respectively. The proportion of patients experiencing that their treatment or follow-up care was affected due to COVID-19 decreased from 28.4% (n = 198) in April 2020 to 14.8% (n = 103) in November 2020. Throughout the pandemic, one or more hospital consultations were postponed in 10.0% (n = 82) of all patients and changed into a teleconsultation in 23.1% (n = 190). The proportion of patients who experienced a higher threshold to contact their general practitioner due to COVID-19 decreased from 29.9% (n = 204) in the first wave to 20.8% (n = 145) in the second wave. In-person consultations remained most preferred in 35.2% (n = 289) of all patients. Nearly half of all patients (48.3%, n = 396) indicated that telehealth would be a useful alternative for in-person consultations in future. CONCLUSION: Perceived access to health care has improved substantially throughout the pandemic. Digital care is well received by patients (being) treated for breast cancer.

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.

SPONGE-assisted versus Trendelenburg position surgery in laparoscopic sigmoid and rectal cancer surgery (SPONGE trial): randomized clinical trial.

BACKGROUND: In minimally invasive surgery of the sigmoid colon and rectum a retractor sponge has been introduced as an alternative to the Trendelenburg position. This randomized clinical trial (RCT) compared postoperative duration of hospital stay and perioperative outcomes in patients with sigmoid or rectal cancer undergoing sponge-assisted versus Trendelenburg position surgery. METHODS: The SPONGE trial is a single-centre RCT nested within the Dutch nationwide prospective observational cohort of patients with colorectal cancer, and follows the Trials within Cohorts (TwiCs) design. Patients with sigmoid or rectal cancer undergoing elective laparoscopic or robotic surgery were randomized to either sponge-assisted or Trendelenburg surgery on a 1:1 basis using block randomization. Duration of postoperative hospital stay was the primary outcome and was compared using the Mann-Whitney U test. Secondary endpoints included the proportion of complications, readmissions, or mortality versus the χ2 test in intention-to-treat and per-protocol analyses. This trial was not blinded for patients in the intervention arm or physicians. RESULTS: Between November 2015 and June 2021, 82 patients were randomized to sponge-assisted surgery and 81 to Trendelenburg surgery. After post-randomization exclusion, 150 patients remained for analyses (75 patients per arm). There was no statistically significant difference in median duration of hospital stay (5 days versus 4 days, respectively; P = 0.06), 30-day postoperative complications (30 per cent versus 31 per cent; P = 1.00), readmission rate (8 per cent versus 15 per cent; P = 0.30), or mortality (0 per cent versus 1 per cent, P = 1.00). The per-protocol analysis showed similar results. No adverse device events were seen. CONCLUSION: Sponge-assisted laparoscopic/robotic surgery does not reduce the duration of hospital stay, or perioperative morbidity or mortality. TRIAL REGISTRATION: NCT02574013 (http://www.clinicaltrials.gov).

Neurovascular-Sparing MR-Guided Adaptive Radiotherapy in Prostate Cancer; Defining the Potential Population for Erectile Function-Sparing Treatment.

BACKGROUND: Magnetic resonance-guided adaptive radiotherapy (MRgRT) enables neurovascular-sparing treatment for localized prostate cancer (PCa). The aim of this treatment is preservation of erectile function by sparing the neurovascular bundles, the internal pudendal arteries, the corpora cavernosa, and the penile bulb. Internal pudendal arteries, corpora cavernosa, and penile bulb sparing can generally be achieved in all patients, but NVB sparing can be challenging due to its proximity to the prostate and is therefore dependent on tumor location. PCa patients that have sufficient erectile function at baseline and favorable tumor characteristics might benefit from this treatment. Currently, it is unclear what proportion of patients are eligible for neurovascular-sparing treatment and to what extent this is technically feasible. AIM: To define the eligibility and technical feasibility for neurovascular-sparing MRgRT in intermediate-risk localized PCa patients. METHODS: A consecutive series of men that received 5 × 7.25 gray (Gy) MRgRT for localized PCa were included. Baseline erectile function was assessed using the International Index of Erectile Function (IIEF)-5 questionnaire. Additionally, the ability of sparing the neurovascular bundles was assessed in all patients. Per neurovascular-sparing protocol, the dominant intraprostatic lesion with a 4 mm isotropic margin should receive 34.44 Gy in ≥ 99% of the volume (i.e., high-dose area). When the high-dose area directly borders or overlaps the NVB because of a dorsolateral position of the dominant intraprostatic lesion, sparing of the NVB was considered not feasible on that side. OUTCOMES: Patient-reported IIEF-5 baseline questionnaires and the technical feasibility of NVB sparing were assessed. RESULTS: Of the 102 men that completed the IIEF-5 questionnaire at baseline, 49.0% of patients reported to have an IIEF-5 score of ≥ 17. In those patients, the NVB could technically have been spared bilaterally in 20.0% and unilaterally in 68.0%. CLINICAL IMPLICATIONS: Our findings define the potential population for neurovascular-sparing MRgRT for localized PCa and indicate the proportion in which the NVB can technically be spared. STRENGTH & LIMITATIONS: The major strength of this study is the prospective collection of data. The limitations include that the neurovascular-sparing feasibility definition is based on pre-clinical planning data. CONCLUSION: A substantial group of 49.0% of patients in our study had mild or no erectile dysfunction at baseline. Of these patients, the NVB could technically have been spared bilaterally in 20.0% and unilaterally in 68.0% during MRgRT. Trials need to assess the effect of neurovascular-sparing MRgRT on erectile function. Teunissen FR, van der Voort van Zyp JRN, Verkooijen HM, et al., Neurovascular-Sparing MR-Guided Adaptive Radiotherapy in Prostate Cancer; Defining the Potential Population for Erectile Function-Sparing Treatment. J Sex Med 2022;19:1196-1200.

The first patient-reported outcomes from the Utrecht Prostate Cohort (UPC): the first platform facilitating 'trials within cohorts' (TwiCs) for the evaluation of interventions for prostate cancer.

PURPOSE: To describe the development and first outcomes of the Utrecht Prostate Cohort (UPC): the first 'trials within cohorts' (TwiCs) platform for prostate cancer (PCa). METHODS: All non-metastasized, histologically proven PCa patients who are planned to receive standard of care are eligible for inclusion in UPC. Patients provide informed consent for the collection of clinical and technical patient data, physician-reported outcomes, and patient-reported outcomes (PROs) up to 10 years post-treatment. Additionally, patients may provide broad consent for future randomization for experimental-intervention trials (TwiCs). Changes in PROs (EPIC-26 questionnaire domains) of the participants who received standard of care were analyzed using Wilcoxon signed-rank tests. RESULTS: In two years, 626 patients were enrolled, 503 (80.4%) of whom provided broad consent for future randomization. Among these, 293 (46.8%) patients underwent magnetic resonance-guided adaptive radiotherapy (MRgRT), 116 (18.5%) CT-guided external beam radiation therapy (EBRT), 109 (17.4%) robot-assisted radical prostatectomy (RARP), and 65 (10.4%) patients opted for active surveillance. Patients treated with MRgRT and CT-guided EBRT showed a transient but significant decline in urinary irritative/obstructive and bowel domain scores at 1-month follow-up. RARP patients showed a significant deterioration of urinary incontinence domain scores between baseline and all follow-up moments and significant improvement of urinary irritative/obstructive domain scores between baseline and 9- and 12-month follow-up. All radical treatment groups showed a significant decline in sexual domain scores during follow-up. Active surveillance patients showed no significant deterioration over time in all domains. CONCLUSION: The first results from the UPC study show distinct differences in PROs between treatment options for PCa. REGISTRATION NO: NCT04228211.