Background
A post-hoc analysis of ABC trials included 34 patients with liver-confined unresectable intrahepatic cholangiocarcinoma (iCCA) who received systemic chemotherapy with gemcitabine and ...cisplatin (gem-cis). The median overall survival (OS) was 16.7 months and the 3-year OS was 2.8%. The aim of this study was to compare patients treated with systemic gem-cis versus hepatic arterial infusion pump (HAIP) chemotherapy for liver-confined unresectable iCCA.
Methods
We retrospectively collected consecutive patients with liver-confined unresectable iCCA who received gem-cis in two centers in the Netherlands to compare with consecutive patients who received HAIP chemotherapy with or without systemic chemotherapy in Memorial Sloan Kettering Cancer Center.
Results
In total, 268 patients with liver-confined unresectable iCCA were included; 76 received gem-cis and 192 received HAIP chemotherapy. In the gem-cis group 42 patients (55.3%) had multifocal disease compared with 141 patients (73.4%) in the HAIP group (
p
= 0.023). Median OS for gem-cis was 11.8 months versus 27.7 months for HAIP chemotherapy (
p
< 0.001). OS at 3 years was 3.5% (95% confidence interval CI 0.0–13.6%) in the gem-cis group versus 34.3% (95% CI 28.1–41.8%) in the HAIP chemotherapy group. After adjusting for male gender, performance status, baseline hepatobiliary disease, and multifocal disease, the hazard ratio (HR) for HAIP chemotherapy was 0.27 (95% CI 0.19–0.39).
Conclusions
This study confirmed the results from the ABC trials that survival beyond 3 years is rare for patients with liver-confined unresectable iCCA treated with palliative gem-cis alone. With HAIP chemotherapy, one in three patients was alive at 3 years
.
Most data on the treatment and outcomes of intrahepatic cholangiocarcinoma (iCCA) derives from expert centers. This study aimed to investigate the treatment and outcomes of all patients diagnosed ...with iCCA in a nationwide cohort.
Data on all patients diagnosed with iCCA between 2010 and 2018 were obtained from the Netherlands Cancer Registry.
In total, 1747 patients diagnosed with iCCA were included. Resection was performed in 292 patients (17%), 548 patients (31%) underwent palliative systemic treatment, and 867 patients (50%) best supportive care (BSC). The OS median and 1-, and 3-year OS were after resection: 37.5 months (31.0–44.0), 79.2%, and 51.6%,; with systemic therapy, 10.0 months (9.2–10.8), 38.4%, and 5.1%, and with BSC 2.2 months (2.0–2.5), 10.4%, and 1.3% respectively. The resection rate for patients who first presented in academic centers was 33% (96/292) compared to 13% (195/1454) in non-academic centers (P < 0.001).
Half of almost 1750 patients with iCCA over an 8 year period did not receive any treatment with a 1-year OS of 10.4%. Three-year survival was about 50% after resection, while long-term survival was rare after palliative treatment. The resection rate was higher in academic centers compared to non-academic centers.
The DRAINAGE trial was a randomized controlled trial comparing preoperative endoscopic (EBD) and percutaneous biliary drainage (PTBD) in patients with potentially resectable, perihilar ...cholangiocarcinoma (pCCA). The aim of this study was to compare the long-term outcomes.
Patients were randomized in four tertiary referral centers. Follow-up data were available for all included patients. Primary outcome was overall survival (OS). Secondary outcomes were readmissions, and re-interventions not including in-trial interventions.
A total of 54 patients were randomized; 27 in both groups. Median follow-up for both groups was 62 months (95% CI 54–70). The median OS was 13 months (95% CI 7.9–18.1) in the EBD and 7 months (95% CI 0.0–17.2) in the PTBD group (P = 0.28). Twenty (37%, n = 8 EBD vs n = 12 PTBD, P = 0.43) of 54 patients were readmitted at least once, mostly due to drainage-related complications (n = 13, 24%). Of note, 14 out of the 54 patients died within the trial. A total of 76 drainage procedures (32 EBD and 44 PTBD) were performed in 28 patients. The median number of stent or drain placements was 2 (2–4) for the EBD group and 2 (1–3) for the PTBD group (P = 0.77).
Although this follow-up study represented a small cohort, no long-term differences in survival, readmissions, and drainage procedures for EBD and PTBD were found, even when comparing the resected and unresected group. However, this study demonstrates the complexity of biliary drainage for patients with potentially resectable pCCA, even in tertiary referral centers.
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Empyema is a well-known complication of pneumonia, with high morbidity and mortality rates. This warrants direct treatment either with antibiotics and chest tube drainage or surgery. With less ...invasive surgical approaches such as uniportal video-assisted thoracoscopic surgery (uVATS), surgical intervention gets a more prominent role early on in the treatment of empyema. The aim of this study was to compare uVATS with the complete VATS (cVATS) approach in empyema, with respect to postoperative complications, hospital length of stay and mortality.
All cases of empyema that were treated surgically in our hospital between 2006 and 2019 were included in a retrospective database. The preferential surgical approach changed from cVATS from 2006 to 2015, towards uVATS from 2016 and on, based on the experience of the surgical team. The database included pre- and postoperative data, as well as peropartive characteristics.
One hundred and thirty-seven patients were treated with cVATS and 49 with uVATS. Apart from a slightly reduced kidney function in the uVATS group (57.3±6.3
. 71.4±17.2 mL/min/1.73 m
, P≤0.001), there were no significant baseline differences in patient characteristics. The duration of uVATS was comparable to cVATS (70±17
. 56±23 min, P=0.240), and with low per- and postoperative complications. The postoperative hospital stay was equal in both groups (19±13
. 20±15 days, P=0.320). There were no statistically significant differences in postoperative complications or death.
Uniportal VATS is a feasible and safe technique for the use in patients with empyema requiring surgery. Even if decortication in stage III empyema is required this can be performed by uniportal VATS.
Background: Immune checkpoint inhibitors (ICI) are routinely used in advanced clear cell renal cell carcinoma (ccRCC). However, a substantial group of patients does not respond to ICI therapy. ...Radiation is a promising approach to increase ICI response rates since it can generate anti-tumor immunity. Targeted radionuclide therapy (TRT) is a systemic radiation treatment, ideally suited for precision irradiation of metastasized cancer. Therefore, the aim of this study is to explore the potential of combined TRT, targeting carbonic anhydrase IX (CAIX) which is overexpressed in ccRCC, using 177LuLu-DOTA-hG250, and ICI for the treatment of ccRCC. Methods: In this study, we evaluated the therapeutic and immunological action of 177LuLu-DOTA-hG250 combined with aPD-1/a-CTLA-4 ICI. First, the biodistribution of 177LuLu-DOTA-hG250 was investigated in BALB/cAnNRj mice bearing Renca-CAIX or CT26-CAIX tumors. Renca-CAIX and CT26-CAIX tumors are characterized by poor versus extensive T-cell infiltration and homogeneous versus heterogeneous PD-L1 expression, respectively. Tumor-absorbed radiation doses were estimated through dosimetry. Subsequently, 177LuLu-DOTA-hG250 TRT efficacy with and without ICI was evaluated by monitoring tumor growth and survival. Therapy-induced changes in the tumor microenvironment were studied by collection of tumor tissue before and 5 or 8 days after treatment and analyzed by immunohistochemistry, flow cytometry, and RNA profiling. Results: Biodistribution studies showed high tumor uptake of 177LuLu-DOTA-hG250 in both tumor models. Dose escalation therapy studies in Renca-CAIX tumor-bearing mice demonstrated dose-dependent anti-tumor efficacy of 177LuLu-DOTA-hG250 and remarkable therapeutic synergy including complete remissions when a presumed subtherapeutic TRT dose (4 MBq, which had no significant efficacy as monotherapy) was combined with aPD-1+aCTLA-4. Similar results were obtained in the CT26-CAIX model for 4 MBq 177LuLu-DOTA-hG250 + a-PD1. Ex vivo analyses of treated tumors revealed DNA damage, T-cell infiltration, and modulated immune signaling pathways in the TME after combination treatment. Conclusions: Subtherapeutic 177LuLu-DOTA-hG250 combined with ICI showed superior therapeutic outcome and significantly altered the TME. Our results underline the importance of investigating this combination treatment for patients with advanced ccRCC in a clinical setting. Further investigations should focus on how the combination therapy should be optimally applied in the future.Background: Immune checkpoint inhibitors (ICI) are routinely used in advanced clear cell renal cell carcinoma (ccRCC). However, a substantial group of patients does not respond to ICI therapy. Radiation is a promising approach to increase ICI response rates since it can generate anti-tumor immunity. Targeted radionuclide therapy (TRT) is a systemic radiation treatment, ideally suited for precision irradiation of metastasized cancer. Therefore, the aim of this study is to explore the potential of combined TRT, targeting carbonic anhydrase IX (CAIX) which is overexpressed in ccRCC, using 177LuLu-DOTA-hG250, and ICI for the treatment of ccRCC. Methods: In this study, we evaluated the therapeutic and immunological action of 177LuLu-DOTA-hG250 combined with aPD-1/a-CTLA-4 ICI. First, the biodistribution of 177LuLu-DOTA-hG250 was investigated in BALB/cAnNRj mice bearing Renca-CAIX or CT26-CAIX tumors. Renca-CAIX and CT26-CAIX tumors are characterized by poor versus extensive T-cell infiltration and homogeneous versus heterogeneous PD-L1 expression, respectively. Tumor-absorbed radiation doses were estimated through dosimetry. Subsequently, 177LuLu-DOTA-hG250 TRT efficacy with and without ICI was evaluated by monitoring tumor growth and survival. Therapy-induced changes in the tumor microenvironment were studied by collection of tumor tissue before and 5 or 8 days after treatment and analyzed by immunohistochemistry, flow cytometry, and RNA profiling. Results: Biodistribution studies showed high tumor uptake of 177LuLu-DOTA-hG250 in both tumor models. Dose escalation therapy studies in Renca-CAIX tumor-bearing mice demonstrated dose-dependent anti-tumor efficacy of 177LuLu-DOTA-hG250 and remarkable therapeutic synergy including complete remissions when a presumed subtherapeutic TRT dose (4 MBq, which had no significant efficacy as monotherapy) was combined with aPD-1+aCTLA-4. Similar results were obtained in the CT26-CAIX model for 4 MBq 177LuLu-DOTA-hG250 + a-PD1. Ex vivo analyses of treated tumors revealed DNA damage, T-cell infiltration, and modulated immune signaling pathways in the TME after combination treatment. Conclusions: Subtherapeutic 177LuLu-DOTA-hG250 combined with ICI showed superior therapeutic outcome and significantly altered the TME. Our results underline the importance of investigating this combination treatment for patients with advanced ccRCC in a clinical setting. Further investigations should focus on how the combination therapy should be optimally applied in the future.
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