BACKGROUND:The standard curative treatment for patients with esophageal cancer is perioperative chemotherapy or preoperative chemoradiotherapy followed by open transthoracic esophagectomy (OTE). ...Robot-assisted minimally invasive thoracolaparoscopic esophagectomy (RAMIE) may reduce complications.
METHODS:A single-center randomized controlled trial was conducted, assigning 112 patients with resectable intrathoracic esophageal cancer to either RAMIE or OTE. The primary endpoint was the occurrence of overall surgery-related postoperative complications (modified Clavien-Dindo classification grade 2–5).
RESULTS:Overall surgery-related postoperative complications occurred less frequently after RAMIE (59%) compared to OTE (80%) risk ratio with RAMIE (RR) 0.74; 95% confidence interval (CI), 0.57–0.96; P = 0.02. RAMIE resulted in less median blood loss (400 vs 568 mL, P <0.001), a lower percentage of pulmonary complications (RR 0.54; 95% CI, 0.34–0.85; P = 0.005) and cardiac complications (RR 0.47; 95% CI, 0.27–0.83; P = 0.006) and lower mean postoperative pain (visual analog scale, 1.86 vs 2.62; P < 0.001) compared to OTE. Functional recovery at postoperative day 14 was better in the RAMIE group RR 1.48 (95% CI, 1.03–2.13; P = 0.038) with better quality of life score at discharge mean difference quality of life score 13.4 (2.0–24.7, p = 0.02) and 6 weeks postdischarge mean difference 11.1 quality of life score (1.0–21.1; P = 0.03). Short- and long-term oncological outcomes were comparable at a medium follow-up of 40 months.
CONCLUSIONS:RAMIE resulted in a lower percentage of overall surgery-related and cardiopulmonary complications with lower postoperative pain, better short-term quality of life, and a better short-term postoperative functional recovery compared to OTE. Oncological outcomes were comparable and in concordance with the highest standards nowadays.
Background
Addition of trastuzumab to first-line palliative chemotherapy in gastroesophageal cancer patients with HER2 overexpression has shown to improve survival. Real-world data on HER2 assessment ...and administration of trastuzumab are lacking. The aim of this study was to assess HER2 testing, trastuzumab administration, and overall survival (OS) in a nationwide cohort of metastatic gastroesophageal cancer patients.
Methods
Data of patients with synchronous metastatic gastroesophageal adenocarcinoma diagnosed in 2010–2016 that received palliative systemic treatment (
n
= 2846) were collected from the Netherlands Cancer Registry and Dutch Pathology Registry. The ToGA trial criteria were used to determine HER2 overexpression. Proportions of HER2 tested patients were analyzed between hospital volume categories using Chi-square tests, and over time using trend analysis. OS was tested using the Kaplan Meier method with log rank test.
Results
HER2 assessment increased annually, from 18% in 2010 to 88% in 2016 (
P
< 0.01). Median OS increased from 6.9 (2010–2013) to 7.9 months (2014–2016;
P
< 0.05). Between the hospitals, the proportion of tested patients varied between 29–100%, and was higher in high-volume hospitals (
P
< 0.01). Overall, 77% of the HER2 positive patients received trastuzumab. Median OS was higher in patients with positive (8.8 months) and negative (7.4 months) HER2 status, compared to non-tested patients (5.6 months;
P
< 0.05).
Conclusion
Increased determination of HER2 and administration of trastuzumab have changed daily practice management of metastatic gastroesophageal cancer patients receiving palliative systemic therapy, and possibly contributed to their improved survival. Further increase in awareness of HER2 testing and trastuzumab administration may improve quality of care and patient outcomes.
In recent years, new treatment options have become available for pancreatic ductal adenocarcinoma (PDAC) including 5-fluorouracil, leucovorin, irinotecan and oxaliplatin. The impact hereof has not ...been assessed in nationwide cohort studies. This population-based study aimed to investigate nationwide trends in incidence, treatment and survival of PDAC.
Patients with PDAC (1997–2016) were included from the Netherlands Cancer Registry. Results were categorised by treatment and by period of diagnosis (1997–2000, 2001–2004, 2005–2008, 2009–2012 and 2013–2016). Kaplan–Meier survival analysis was used to calculate overall survival.
In a national cohort of 36,453 patients with PDAC, the incidence increased from 12.1 (1997–2000) to 15.3 (2013–2016) per 100,000 (p < 0.001), whereas median overall survival increased from 3.1 to 3.8 months (p < 0.001). Over time, the resection rate doubled (8.3%–16.6%, p-trend<0.001), more patients received adjuvant chemotherapy (3.0%–56.2%, p-trend<0.001) and 3-year overall survival following resection increased (16.9%–25.4%, p < 0.001). Over time, the proportion of patients with metastatic disease who received palliative chemotherapy increased from 5.3% to 16.1% (p-trend<0.001), whereas 1-year survival improved from 13.3% to 21.2% (p < 0.001). The proportion of patients who only received supportive care decreased from 84% to 61% (p-trend<0.001).
The incidence of PDAC increased in the past two decades. Resection rates and use of adjuvant or palliative chemotherapy increased with improved survival in these patients. In all patients with PDAC, however, the survival benefit of 3 weeks is negligible because the majority of patients only received supportive care.
•The incidence of pancreatic ductal adenocarcinoma increased from 1997 to 2016.•Resection rates and use of adjuvant or palliative chemotherapy increased.•The majority of patients still received supportive care only.•Survival improved in patients who underwent resection or systemic treatment.•The survival of all patients improved with only 3 weeks.
A globally accepted standard first-line chemotherapy regimen in advanced esophagogastric cancer (AEGC) is not clearly established. We conducted a systematic review to investigate the efficacy and ...safety of first-line chemotherapy using Network meta-analysis (NMA).
Medline, EMBASE, CENTRAL, and conferences were searched until June 2015 for randomized controlled trials that compared regimens containing: fluoropyrimidine (F), platinum (cisplatin C and oxaliplatin Ox), taxane (T), anthracycline (A), irinotecan (I), or methotrexate (M). Direct and indirect evidence for overall survival (OS) and progression-free-survival (PFS) were combined using random-effects NMA on the hazard ratio (HR) scale and calculated as combined hazard ratios and 95% credible intervals (CrIs).
The NMA incorporated 17 chemotherapy regimens with 37 direct comparisons between regimens for OS (50 studies, n = 10 249) and 29 direct comparisons for PFS (34 studies, n = 7795). Combining direct and indirect effects showed increased efficacy for fluoropyrimidine noncisplatin doublets (F-doublets) over cisplatin doublets (C-doublets): FI vs CF (combined HR = 0.85, 95% CrI = 0.71 to 0.99), FOx vs CF (combined HR = 0.83, 95% CrI = 0.71 to 0.98) in OS and FOx vs CF (combined HR = 0.82, 95% CrI = 0.66 to 0.99) in PFS. Anthracycline-containing triplets (A-triplets: ACF, AFOx, AFM) and TCF triplet showed no benefit over F-doublets in OS and PFS. The triplet FOxT showed increased PFS vs F-doublets FT (combined HR = 0.61, 95% CrI = 0.38 to 0.99), FI (combined HR = 0.62, 95% CrI = 0.38 to 0.99), and FOx (combined HR = 0.67, 95% CrI = 0.44 to 0.99). Increased grade 3 to 4 toxicity was found for CF vs F-doublets, for ACF vs FI for TCF vs CF, and for FOxT vs FOx.
Based on efficacy and toxicity, F-doublets FOx, FI, and FT are preferred as first-line treatment for AEGC compared with C-doublets, A-triplets, and TCF. FOxT is the most promising triplet.
Background: Population-based data on distal cholangiocarcinoma (DCC) from the Western world are not available, albeit essential to identify areas for improvement. This study investigated the ...incidence, treatment and outcomes, including time trends and predictors for survival, in a nationwide cohort of DCC.
Methods: This is a retrospective cohort study of patients diagnosed with DCC (2009-2016) derived from the Netherlands Cancer Registry. Overall survival (OS) and its predictors were analyzed using Kaplan-Meier and Cox regression analysis. Time trends (2009-2012 versus 2013-2016) were assessed.
Results: Overall, 1338 patients with DCC were included, with 1-, 3- and 5-year OS of 46%, 18%, and 11%. Incidence of DCC was 0.55-0.90 per 100.000 per year. Median OS was 10.4 months across all stages; 21.9 months for resected (n = 620, 46.3%), 6.7 months for unresected nonmetastatic (n = 445, 33.3%), and 3.6 months for metastatic DCC (n = 273, 20.4%) (p < .001). After resection, 30-day mortality was 4.8% and 90-day mortality 7.7%. Patients with metastatic DCC who received chemotherapy (n = 78, 28.6%) had a median OS of 8.2 versus 2.8 months for those not treated (p < .001). Over time, resection rates (53.6% to 61.7%, p = .008) and use of palliative chemotherapy in metastatic DCC (22.3% to 32.9%, p = .05) increased, without improvement in OS (10.3 vs 10.6 months, p = .55). Independent poor prognostic factors for OS in resected disease were increasing age, pT3/T4 stage, higher lymph node ratio, poor differentiation, and R1 resection.
Conclusions: In a nationwide cohort of DCC, resection rates and the use of chemotherapy increased whereas OS remained stable at 10.4 months.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Prior models have been developed to predict survival for patients with esophagogastric cancer undergoing curative treatment or first‐line chemotherapy (SOURCE models). Comprehensive clinical ...prediction models for patients with esophagogastric cancer who will receive second‐line chemotherapy or best supportive care are currently lacking. The aim of our study was to develop and internally validate a new clinical prediction model, called SOURCE beyond first‐line, for survival of patients with metastatic esophagogastric adenocarcinoma after failure of first‐line palliative systemic therapy. Patients with unresectable or metastatic esophageal or gastric adenocarcinoma (2015‐2017) who received first‐line systemic therapy (N = 1067) were selected from the Netherlands Cancer Registry. Patient, tumor and treatment characteristics at primary diagnosis and at progression of disease were used to develop the model. A Cox proportional hazards regression model was developed through forward and backward selection using Akaike's Information Criterion. The model was internally validated through 10‐fold cross‐validations to assess performance. Model discrimination (C‐index) and calibration (slope and intercept) were used to evaluate performance of the complete and cross‐validated models. The final model consisted of 11 patient tumor and treatment characteristics. The C‐index was 0.75 (0.73‐0.78), calibration slope 1.01 (1.00‐1.01) and calibration intercept 0.01 (0.01‐0.02). Internal cross‐validation of the model showed that the model performed adequately on unseen data: C‐index was 0.79 (0.77‐0.82), calibration slope 0.93 (0.85‐1.01) and calibration intercept 0.02 (−0.01 to 0.06). The SOURCE beyond first‐line model predicted survival with fair discriminatory ability and good calibration.
What's new?
Patients with metastatic esophagogastric cancer generally have poor survival. Here, the authors present a model for predicting survival after failure of first‐line palliative systemic treatment. They collected data from 1067 patients in the Netherlands Cancer Registry who had unresectable or metastatic esophageal or gastric adenocarcinoma. Unlike existing models, this model includes information about second‐line chemotherapies and best supportive care, and was developed on a large number of patients. The final model included 11 different characteristics of the patient, tumor, and treatment, and could help patients and providers make informed decisions about starting second‐line therapies.
The CROSS trial established neoadjuvant chemoradiotherapy (nCRT) for patients with resectable esophageal adenocarcinoma (rEAC). In the PERFECT trial, we investigated the feasibility and efficacy of ...nCRT combined with programmed-death ligand-1 (PD-L1) inhibition for rEAC.
Patients with rEAC received nCRT according to the CROSS regimen combined with five cycles of atezolizumab (1,200 mg). The primary endpoint was the feasibility of administering five cycles of atezolizumab in ≥75% patients. A propensity score-matched nCRT cohort was used to compare pathologic response, overall survival, and progression-free survival. Exploratory biomarker analysis was performed on repeated tumor biopsies.
We enrolled 40 patients of whom 85% received all cycles of atezolizumab. Immune-related adverse events of any grade were observed in 6 patients. In total, 83% proceeded to surgery. Reasons for not undergoing surgery were progression (
= 4), patient choice (
= 2), and death (
= 1). The pathologic complete response rate was 25% (10/40). No statistically significant difference in response or survival was found between the PERFECT and the nCRT cohort. Baseline expression of an established IFNγ signature was higher in responders compared with nonresponders (
= 0.043). On-treatment nonresponders showed either a high number of cytotoxic lymphocytes (CTL) with a transcriptional signature consistent with expression of immune checkpoints, or a low number of CTLs.
Combining nCRT with atezolizumab is feasible in patients with rEAC. On the basis of our exploratory biomarker study, future studies are necessary to elucidate the potential of neoadjuvant immunotherapy in patient subgroups.
.
New treatment options and centralization of surgery have improved survival for patients with non‐metastatic esophageal or gastric cancer. It is unknown, however, which patients benefitted the most ...from treatment advances. The aim of this study was to identify best‐case, typical and worst‐case scenarios in terms of survival time, and to assess if survival associated with these scenarios changed over time. Patients with non‐metastatic potentially resectable esophageal or gastric cancer diagnosed between 2006 and 2020 were selected from the Netherlands Cancer Registry. Best‐case (20th percentile), upper‐typical (40th percentile), typical (median), lower‐typical (60th percentile) and worst‐case (80th percentile) survival scenarios were defined, and regression analysis was used to investigate the change in survival time for each scenario across years. For patients with esophageal cancer (N = 24 352) survival time improved on average 12.0 (until 2011), 1.5 (until 2018), 0.7, 0.4 and 0.2 months per year for the best‐case, upper‐typical, median, lower‐typical and worst‐case scenario, respectively. For patients with gastric cancer (N = 9993) survival time of the best‐case scenario remained constant, whereas the upper‐typical, median, lower‐typical and worst‐case scenario improved on average with 1.0 (until 2018), 0.5, 0.2 and 0.2 months per year, respectively. Subgroup analyses showed that, survival scenarios improved for nearly all patients across treatment groups and for patients with squamous cell carcinomas or adenocarcinomas. Survival improved for almost all patients suggesting that in clinical practice the vast majority of patients benefitted from treatment advances. The clinically most meaningful survival advantage was observed for the best‐case scenario of esophageal cancer.
What's new?
New treatment options and centralization of surgery have improved survival for patients with non‐metastatic esophageal or gastric cancer. It is unknown, however, which patients most benefited from treatment advances. This study analyzed survival trends in patients with non‐metastatic esophagogastric cancer in the Netherlands over the past 15 years using survival scenarios based on survival percentiles in addition to median survival. The findings showed that survival improved for almost all patients, suggesting that the vast majority of patients benefited from treatment advances in clinical practice. The greatest clinically meaningful survival advantage was observed for the best‐case survival scenario in esophageal cancer.
The optimal first‐line palliative systemic treatment strategy for metastatic esophagogastric cancer is not well defined. The aim of our study was to explore real‐world use of first‐line systemic ...treatment in esophagogastric cancer and assess the effect of treatment strategy on overall survival (OS), time to failure (TTF) of first‐line treatment and toxicity. We selected synchronous metastatic esophagogastric cancer patients treated with systemic therapy (2010–2016) from the nationwide Netherlands Cancer Registry (n = 2,204). Systemic treatment strategies were divided into monotherapy, doublet and triplet chemotherapy, and trastuzumab‐containing regimens. Data on OS were available for all patients, on TTF for patients diagnosed from 2010 to 2015 (n = 1,700), and on toxicity for patients diagnosed from 2010 to 2014 (n = 1,221). OS and TTF were analyzed using multivariable Cox regression, with adjustment for relevant tumor and patient characteristics. Up to 45 different systemic treatment regimens were found to be administered, with a median TTF of 4.6 and OS of 7.5 months. Most patients (45%) were treated with doublet chemotherapy; 34% received triplets, 10% monotherapy and 10% a trastuzumab‐containing regimen. The highest median OS was found in patients receiving a trastuzumab‐containing regimen (11.9 months). Triplet chemotherapy showed equal survival rates compared to doublets (OS: HR 0.92, 95%CI 0.83–1.02; TTF: HR 0.92, 95%CI 0.82–1.04) but significantly more grade 3–5 toxicity than doublets (33% vs. 21%, respectively). In conclusion, heterogeneity of first‐line palliative systemic treatment in metastatic esophagogastric cancer patients is striking. Based on our data, doublet chemotherapy is the preferred treatment strategy because of similar survival and less toxicity compared to triplets.
What's new?
Metastatic esophagogastric cancer can't be cured, but palliative therapy can improve patients’ quality of life and survival. However, there's no consensus regarding the optimal first‐line palliative systemic therapy for metastatic esophagogastric cancer. Here, the authors evaluated real‐world use of first‐line systemic treatments. The retrospective study included a cohort of 2,204 metastatic patients and found 45 different treatment regimens administered. Patients that received doublet and triplet chemotherapy had similar survival, with triplet patients experiencing higher toxicity. Monotherapy produced significantly worse overall survival and only modest reduction in toxicity. These findings support doublet therapy as the optimal first‐line treatment strategy.
The relation between the primary origin of metastasised pancreatic ductal adenocarcinoma (PDAC)—head, body or tail—metastatic patterns and outcomes has not yet been investigated in large ...population-based studies.
Patients with metastasised PDAC at diagnosis from the Netherlands Cancer Registry were included (2005–2015). We compared number of metastatic organ sites (1, 2, ≥3) and specific metastatic organ sites (peritoneum, liver, lung and extra-regional lymph nodes) for the different primary tumour locations. Cox regression analyses were used to determine the association of tumour location and metastatic organ site(s) with overall survival.
Overall, we included 9952 patients with metastasised PDAC. The primary origin was head in 5644 (57%), body in 1671 (17%) and tail in 2637 (26%) patients. Differences between primary origins were the number of metastatic organ sites (proportions ≥3 sites for head: 4%, for body: 8% and for tail: 13%, p < 0.0001) and peritoneal metastases (present in 13% for head, 24% for body and 30% for tail; p < 0.0001). Median overall survival was 2.6 months for head PDAC (reference), 2.4 months for body PDAC (HR 1.02 0.97–1.08) and 1.9 months for tail PDAC (HR 1.20 1.15–1.26). Of patients with one metastatic organ site, the worst survival compared with other sites was seen with liver only metastases (2.5 months vs. 2.7–5.1 months), and the best survival for patients, with extra-regional lymph node only metastases (5.1 months).
Metastatic patterns differ among the primary origins for PDAC with metastasised tail tumours having more metastatic sites, more often peritoneal metastases and worse survival.
•In total, 9952 patients with metastasised pancreatic cancer were investigated.•Metastatic patterns differ among the primary origins for pancreatic cancer.•Metastasised tail cancers have more metastatic sites than the head or body.•Metastasised tail cancers have more peritoneal metastases than the head or body.•Overall survival was worst for patients with metastasised tail cancer.
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