Background
Studies comparing upfront surgery with neoadjuvant treatment in pancreatic cancer may report only patients who underwent resection and so survival will be skewed. The aim of this study was ...to report survival by intention to treat in a comparison of upfront surgery versus neoadjuvant treatment in resectable or borderline resectable pancreatic cancer.
Methods
MEDLINE, Embase and the Cochrane Library were searched for studies reporting median overall survival by intention to treat in patients with resectable or borderline resectable pancreatic cancer treated with or without neoadjuvant treatment. Secondary outcomes included overall and R0 resection rate, pathological lymph node rate, reasons for unresectability and toxicity of neoadjuvant treatment.
Results
In total, 38 studies were included with 3484 patients, of whom 1738 (49·9 per cent) had neoadjuvant treatment. The weighted median overall survival by intention to treat was 18·8 months for neoadjuvant treatment and 14·8 months for upfront surgery; the difference was larger among patients whose tumours were resected (26·1 versus 15·0 months respectively). The overall resection rate was lower with neoadjuvant treatment than with upfront surgery (66·0 versus 81·3 per cent; P < 0·001), but the R0 rate was higher (86·8 (95 per cent c.i. 84·6 to 88·7) versus 66·9 (64·2 to 69·6) per cent; P < 0·001). Reported by intention to treat, the R0 rates were 58·0 and 54·9 per cent respectively (P = 0·088). The pathological lymph node rate was 43·8 per cent after neoadjuvant therapy and 64·8 per cent in the upfront surgery group (P < 0·001). Toxicity of at least grade III was reported in up to 64 per cent of the patients.
Conclusion
Neoadjuvant treatment appears to improve overall survival by intention to treat, despite lower overall resection rates for resectable or borderline resectable pancreatic cancer.
PROSPERO registration number: CRD42016049374.
Improved survival with neoadjuvant treatment
Surgical resection followed by adjuvant mFOLFIRINOX (5-fluorouracil with leucovorin, irinotecan, and oxaliplatin) is currently the standard of care for patients with resectable pancreatic cancer. The ...main concern regarding adjuvant chemotherapy is that only half of patients actually receive adjuvant treatment. Neoadjuvant chemotherapy, on the other hand, guarantees early systemic treatment and may increase chemotherapy use and thereby improve overall survival. Furthermore, it may prevent futile surgery in patients with rapidly progressive disease. However, some argue that neoadjuvant therapy delays surgery, which could lead to progression towards unresectable disease and thus offset the potential benefits. Comparison of perioperative (i.e., neoadjuvant and adjuvant) with (only) adjuvant administration of mFOLFIRINOX in a randomized controlled trial (RCT) is needed to determine the optimal approach.
This multicenter, phase 3, RCT will include 378 patients with resectable pancreatic ductal adenocarcinoma with a WHO performance status of 0 or 1. Patients are recruited from 20 Dutch centers and three centers in Norway and Sweden. Resectable pancreatic cancer is defined as no arterial contact and ≤ 90 degrees venous contact. Patients in the intervention arm are scheduled for 8 cycles of neoadjuvant mFOLFIRINOX followed by surgery and 4 cycles of adjuvant mFOLFIRINOX (2-week cycle of oxaliplatin 85 mg/m
, leucovorin 400 mg/m
, irinotecan 150 mg/m
at day 1, followed by 46 h continuous infusion of 5-fluorouracil 2400 g/m
). Patients in the comparator arm start with surgery followed by 12 cycles of adjuvant mFOLFIRINOX. The primary outcome is overall survival by intention-to-treat. Secondary outcomes include progression-free survival, resection rate, quality of life, adverse events, and surgical complications. To detect a hazard ratio of 0.70 with 80% power, 252 events are needed. The number of events is expected to be reached after the inclusion of 378 patients in 36 months, with analysis planned 18 months after the last patient has been randomized.
The multicenter PREOPANC-3 trial compares perioperative mFOLFIRINOX with adjuvant mFOLFIRINOX in patients with resectable pancreatic cancer.
Clinical Trials: NCT04927780. Registered June 16, 2021.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Locally advanced pancreatic cancer (LAPC) is associated with a very poor prognosis. Current palliative (radio)chemotherapy provides only a marginal survival benefit of 2–3 months. Several ...innovative local ablative therapies have been explored as new treatment options. This systematic review aims to provide an overview of the clinical outcomes of these ablative therapies.
Methods
A systematic search in PubMed, Embase and the Cochrane Library was performed to identify clinical studies, published before 1 June 2014, involving ablative therapies in LAPC. Outcomes of interest were safety, survival, quality of life and pain.
Results
After screening 1037 articles, 38 clinical studies involving 1164 patients with LAPC, treated with ablative therapies, were included. These studies concerned radiofrequency ablation (RFA) (7 studies), irreversible electroporation (IRE) (4), stereotactic body radiation therapy (SBRT) (16), high‐intensity focused ultrasound (HIFU) (5), iodine‐125 (2), iodine‐125–cryosurgery (2), photodynamic therapy (1) and microwave ablation (1). All strategies appeared to be feasible and safe. Outcomes for postoperative, procedure‐related morbidity and mortality were reported only for RFA (4–22 and 0–11 per cent respectively), IRE (9–15 and 0–4 per cent) and SBRT (0–25 and 0 per cent). Median survival of up to 25·6, 20·2, 24·0 and 12·6 months was reported for RFA, IRE, SBRT and HIFU respectively. Pain relief was demonstrated for RFA, IRE, SBRT and HIFU. Quality‐of‐life outcomes were reported only for SBRT, and showed promising results.
Conclusion
Ablative therapies in patients with LAPC appear to be feasible and safe.
Burn out
Background
Surgeons have traditionally been reluctant to perform total pancreatectomy because of concerns for brittle diabetes and poor quality of life (QoL). Several recent studies have suggested ...that outcomes following total pancreatectomy have improved, but a systematic review is lacking.
Methods
A systematic review was undertaken of studies reporting on outcomes after total pancreatectomy for all indications, except chronic pancreatitis. PubMed, EMBASE (Ovid), and Cochrane Library were searched (2005–2018). Endpoints included functional outcome and QoL.
Results
A total of 21 studies, including 1536 patients, fulfilled the eligibility criteria. During a median follow‐up of 20·8 (range 1·5–96·0) months, 18·6 per cent (45 of 242 patients) were readmitted for endocrine‐related morbidity, with associated mortality in 1·6 per cent (6 of 365 patients). No diabetes‐related mortality was reported in studies including only patients treated after 2005. Symptoms related to exocrine insufficiency were reported by 43·5 per cent (143 of 329 patients) during a median follow‐up of 15·9 (1·5–96·0) months. Overall QoL, reported by 102 patients with a median follow‐up of 28·6 (6·0–66·0) months, using the EORTC QLQ‐C30 questionnaire, showed a moderately reduced summary score of 76 per cent, compared with a general population score of 86 per cent (P = 0·004).
Conclusion
Overall QoL after total pancreatectomy is affected adversely, in particular by the considerable impact of diarrhoea that requires better treatment. There is also room for improvement in the management of diabetes after total pancreatectomy, particularly with regards to prevention of diabetes‐related morbidity.
Antecedentes
Los cirujanos tradicionalmente se han mostrado reacios a realizar una pancreatectomía total (total pancreatectomy, TP) debido a la preocupación por la aparición de diabetes lábil y la mala calidad de vida (quality of life, QoL). Varios estudios recientes han sugerido que el resultado de la TP ha mejorado, sin embargo no existe una revisión sistemática.
Métodos
Se ha realizado una revisión sistemática de los estudios que incluían los resultados después de una TP efectuada para todas las indicaciones, excepto para una pancreatitis crónica. Se realizaron búsquedas en PubMed, Embase (Ovid) y Cochrane Library (2005‐2018). Los resultados principales eran el resultado funcional y la calidad de vida.
Resultados
En total, 21 estudios cumplieron los criterios de elegibilidad, incluyendo 1.536 pacientes que se habían sometido a una TP. Durante una mediana de seguimiento de 20,8 meses (rango 1,5‐96,0), el 18,6% de los pacientes (45 de 242) fueron reingresados por morbilidad relacionada con la función endocrina, con una mortalidad asociada del 1,6% (6 de 365 pacientes). No hubo mortalidad relacionada con la diabetes en los estudios que incluyeron solo aquellos pacientes tratados después de 2005. Se observaron síntomas relacionados con insuficiencia exocrina en un 43,5% de los pacientes (143 de 329) durante una mediana de seguimiento de 15,9 meses (rango 1,5‐96,0). La calidad de vida global, informada para 102 pacientes con una mediana de seguimiento de 28,6 meses (rango 6,0‐66,0) utilizando el cuestionario EORTC QLQ‐C30, mostró una puntuación sumatoria moderadamente reducida del 76% en comparación con la puntuación del 86% para la población general (P = 0,004).
Conclusión
Es necesario seguir mejorando el manejo de la diabetes después de la TP, sobre todo en lo que respecta a la prevención de la morbilidad relacionada con la diabetes. La calidad de vida global se ve afectada después de la TP y, especialmente, el impacto de la diarrea es considerable y requiere mejorar este aspecto en el futuro.
Report of a systematic review of outcomes following total pancreatectomy.
Diabetes and diarrhea should be improved
In pancreatic cancer, preoperative biliary drainage (PBD) increases complications compared with surgery without PBD, demonstrated by a recent randomised controlled trial (RCT). This outcome might be ...related to the plastic endoprosthesis used. Metal stents may reduce the PBD-related complications risk.
A prospective multicentre cohort study was performed including patients with obstructive jaundice due to pancreatic cancer, scheduled to undergo PBD before surgery. This cohort was added to the earlier RCT (ISRCTN31939699). The RCT protocol was adhered to, except PBD was performed with a fully covered self-expandable metal stent (FCSEMS). This FCSEMS cohort was compared with the RCT's plastic stent cohort. PBD-related complications were the primary outcome. Three-group comparison of overall complications including early surgery patients was performed.
53 patients underwent PBD with FCSEMS compared with 102 patients treated with plastic stents. Patients' characteristics did not differ. PBD-related complication rates were 24% in the FCSEMS group vs 46% in the plastic stent group (relative risk of plastic stent use 1.9, 95% CI 1.1 to 3.2, p=0.011). Stent-related complications (occlusion and exchange) were 6% vs 31%. Surgical complications did not differ, 40% vs 47%. Overall complication rates for the FCSEMS, plastic stent and early surgery groups were 51% vs 74% vs 39%.
For PBD in pancreatic cancer, FCSEMS yield a better outcome compared with plastic stents. Although early surgery without PBD remains the treatment of choice, FCSEMS should be preferred over plastic stents whenever PBD is indicated.
Dutch Trial Registry (NTR3142).
Background
Textbook outcome (TO) is a composite variable that can define the quality of pancreatic surgery. The aim of this study is to evaluate TO after pancreatoduodenectomy (PD) for nonfunctioning ...pancreatic neuroendocrine tumors (NF-PanNETs).
Patients and Methods
All patients who underwent PD for NF-PanNETs (2007–2016) in different centers were included in this retrospective study. TO was defined as the absence of severe postoperative complications and mortality, length of hospital stay ≤ 19 days, R0 resection, and at least 12 lymph nodes harvested.
Results
Overall, 477 patients were included. The TO rate was 32%. Tumor size odds ratio (OR) 1.696;
p
= 0.013, a minimally invasive approach (OR 12.896;
p
= 0.001), and surgical volume (OR 2.062;
p
= 0.023) were independent predictors of TO. The annual frequency of PDs increased over time as well as the overall rate of TO. At a median follow-up of 44 months, patients who achieved TO had similar disease-free (
p
= 0.487) and overall survival (
p
= 0.433) rates compared with patients who did not achieve TO. TO rate in patients with NF-PanNET > 2 cm was 35% versus 27% in patients with NF-PanNET ≤ 2 cm (
p
= 0.044). Considering only NF-PanNETs > 2 cm, patients with TO and those without TO had comparable 5-year overall survival rates (
p
= 0.766)
Conclusions
TO is achieved in one-third of patients after PD for NF-PanNETs and is not associated with a benefit in terms of long-term survival.
The objective of this study was to derive and validate a prognostic nomogram to predict disease-specific survival (DSS) after a curative intent resection of perihilar cholangiocarcinoma (PHC).
A ...nomogram was developed from 173 patients treated at Memorial Sloan Kettering Cancer Center (MSKCC), New York, USA. The nomogram was externally validated in 133 patients treated at the Academic Medical Center (AMC), Amsterdam, The Netherlands. Prognostic accuracy was assessed with concordance estimates and calibration, and compared with the American Joint Committee on Cancer (AJCC) staging system. The nomogram will be available as web-based calculator at mskcc.org/nomograms.
For all 306 patients, the median overall survival (OS) was 40 months and the median DSS 41 months. Median follow-up for patients alive at last follow-up was 48 months. Lymph node involvement, resection margin status, and tumor differentiation were independent prognostic factors in the derivation cohort (MSKCC). A nomogram with these prognostic factors had a concordance index of 0.73 compared with 0.66 for the AJCC staging system. In the validation cohort (AMC), the concordance index was 0.72, compared with 0.60 for the AJCC staging system. Calibration was good in the derivation cohort; in the validation cohort patients had a better median DSS than predicted by the model.
The proposed nomogram to predict DSS after curative intent resection of PHC had a better prognostic accuracy than the AJCC staging system. Calibration was suboptimal because DSS differed between the two institutions. The nomogram can inform patients and physicians, guide shared decision making for adjuvant therapy, and stratify patients in future randomized, controlled trials.
Tumor location of extrahepatic cholangiocarcinoma (CCA) might influence survival after resection.
A consecutive series of 175 patients who had undergone a potentially curative resection of ...extrahepatic CCA was analyzed. We calculated concordance indices of different constructed prognostic models for survival including TNM (tumour–node–metastasis) staging and developed a nomogram of the most sensitive model.
Overall cancer-specific survival rates were 83%, 58%, and 26% at 1, 2, and 5 years, respectively. Cancer-specific survival according to location was 42% for proximal, 23% for mid, and 19% for distal CCA after 5 years. Tumor location was not an independent significant predictor (P = 0.06). A prognostic model using all potential prognostic variables predicted survival better compared with TNM staging (concordance index 0.65 versus 0.63). A reduced model containing only lymph node status, microscopically residual tumor status, and tumor differentiation grade, also outperformed TNM staging (concordance index 0.66).
Tumor location of extrahepatic CCA does not independently predict cancer-specific survival after resection. We developed a nomogram, based on a prognostic model with lymph node status, microscopically residual tumor status of resection margins, and tumor differentiation grade, that predicted survival better than TNM staging.
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