CIREL, a prospective, Europe-wide, observational study aimed to assess the real-world feasibility and tolerability of irinotecan-based transarterial chemoembolization (LP-irinotecan TACE) for ...unresectable colorectal cancer liver metastases with regard to the treatment plan and adverse events (AEs). CIREL enrolled 152 eligible patients (≥18 years) with liver-only or dominant metastases treated with LP-irinotecan TACE following a multidisciplinary tumor board decision. Data were prospectively collected for baseline, the number of planned and performed sessions, and technical information and safety according to CTCAE 4.03/5.0. Results from 351 analyzed treatment sessions showed technical success for 99% of sessions, and 121 patients (79%) completed all planned sessions. Further, 60% of sessions were performed using opioids, 4% intra-arterial anesthetics, and 25% both. Additionally, 60% of patients experienced at least one peri-interventional AE of any grade; 8% of grade 3−4. Occurrence of AEs was related to larger liver-involvement (p < 0.001), bi-lobar disease (p = 0.002), and larger beads (p < 0.001). Using corticosteroids together with antiemetics showed reduced and lower grade vomiting (p = 0.01). LP-irinotecan TACE was tolerated well and had a high proportion of completed treatment plans. This minimally invasive locoregional treatment can be used together with concomitant systemic therapy or ablation.
The EGFR (epithelial growth factor receptor) ligands amphiregulin (AREG) and epiregulin (EREG) have been considered as predictors for EGFR-antibody efficacy. The effect of AREG and EREG expression ...levels in primary tumor samples on the outcome of bevacizumab-treated patients is unknown.
Formalin-fixed paraffin-embedded (FFPE) tumor samples from surgically removed primaries of the AIO KRK-0207 trial have been tested for AREG and EREG expression. The AIO KRK-0207 trial was a randomized phase-3 study to investigate the best maintenance strategy after oxaliplatin/fluoropyrimidine plus bevacizumab induction treatment in patients with mCRC. Association of AREG and EREG levels with outcome parameters were investigated, taking into account RAS and BRAF mutations.
A total of 331 tumor samples had measurable AREG and EREG tissue levels. In the total cohort using continuous expression levels, higher logAREG and logEREG levels were associated with a significant longer overall survival (OS) (HR 0.80;
= 0.003 and HR 0.78;
= 0.001, respectively). The subgroup of BRAF mutant tumors displayed significantly lower AREG and EREG levels compared to wild-type tumors. The prognostic effect of AREG and EREG expression was limited to the double wild-type subpopulation, whereas in the RAS mutant and BRAF mutant subgroups no prognostic effect was detected.
Low logAREG and logEREG levels are associated with a shorter OS in oxaliplatin/fluoropyrimidine plus bevacizumab treated patients. As low AREG and EREG level are associated with BRAF mutations, the prognostic value of EREG and AREG levels is limited to the RAS and BRAF wild-type subpopulation.
New therapeutic options for refractory metastatic colorectal cancer (mCRC) include trifluridine/tipiracil (TAS-102) and regorafenib. However, the optimal chemotherapeutic regimen for use of each ...agent beyond the second line for patients with mCRC remains unclear and various factors may influence treatment decision. Available efficacy data suggest treatment with either trifluridine/tipiracil or regorafenib may be appropriate as both can extend patient survival. Thus, the safety profiles of each agent, along with patient performance status, are likely to determine treatment choice. The safety profiles of trifluridine/tipiracil and regorafenib are markedly different: higher levels of non-haematological adverse events such as fatigue, diarrhoea, hypertension and hand-foot skin reaction are reported with regorafenib, while haematological events such as neutropaenia are more common with trifluridine/tipiracil. In general, neutropaenia is a manageable treatment-related toxicity, while hand-foot skin reaction can be troublesome for patients, affecting their ability to carry out everyday activities and get on with their lives, while also affecting treatment adherence. Thus, the occurrence of any potential adverse effects and patient adherence should be closely monitored at each clinic visit. As quality of life is an important issue for patients with mCRC, it is important to balance extended survival and the likely quality of this extended life. Likewise, discussing possible side effects along with treatment expectations with patients can greatly facilitate adherence to therapy, and ultimately improve patients’ quality of life and eventual clinical outcomes.
Transarterial radioembolization (TARE) with Yttrium-90 resin microspheres is an established treatment option for patients with hepatocellular carcinoma (HCC). However, optimising treatment ...application and patient selection remains challenging. We report here on the effectiveness, safety and prognostic factors, including dosing methods, associated with TARE for HCC in the prospective observational CIRT study.
We analysed 422 patients with HCC enrolled between Jan 2015 and Dec 2017, with follow-up visits every 3 months for up to 24 months after first TARE. Patient characteristics and treatment-related data were collected at baseline; adverse events and time-to-event data (overall survival OS, progression-free survival PFS and hepatic PFS) were collected at every 3-month follow-up visit. We used the multivariable Cox proportional hazard model and propensity score matching to identify independent prognostic factors for effectiveness outcomes.
The median OS was 16.5 months, the median PFS was 6.1 months, and the median hepatic PFS was 6.7 months. Partition model dosimetry resulted in improved OS compared to body surface area calculations on multivariable analysis (hazard ratio 0.65; 95% CI 0.46-0.92; p = 0.0144), which was confirmed in the exact matching propensity score analysis (hazard ratio 0.56; 95% CI 0.35-0.89; p = 0.0136). Other independent prognostic factors for OS were ECOG-performance status >0 (p = 0.0018), presence of ascites (p = 0.0152), right-sided tumours (p = 0.0002), the presence of portal vein thrombosis (p = 0.0378) and main portal vein thrombosis (p = 0.0028), ALBI grade 2 (p = 0.0043) and 3 (p = 0.0014). Adverse events were recorded in 36.7% of patients, with 9.7% of patients experiencing grade 3 or higher adverse events.
This large prospective observational dataset shows that TARE is an effective and safe treatment in patients with HCC. Using partition model dosimetry was associated with a significant improvement in survival outcomes.
Transarterial radioembolization (TARE) is a form of localised radiation therapy and is a potential treatment option for primary liver cancer. We observed how TARE was used in real-life clinical practice in various European countries and if any factors predict how well the treatment performs. We found that when a more complex but personalised method to calculate the applied radiation activity was used, the patient responded better than when a more generic method was used. Furthermore, we identified that general patient health, ascites and liver function can predict outcomes after TARE.
NCT02305459.
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•CIRT is a large, European-wide multicentre prospective observational study.•Partition model dosimetry is associated with improved overall survival compared to the standard body surface area model.•ALBI grades, ECOG status, ascites, portal vein thrombosis and tumour location predict survival outcomes after TARE.•TARE is a safe treatment associated with a low occurence of adverse events.
Peritoneal carcinomatosis is regarded as a common sign of advanced tumor stage, tumor progression or local recurrence of appendiceal and colorectal cancer and is generally associated with poor ...prognosis. Although survival of patients with advanced stage CRC has markedly improved over the last 20 years with systemic treatment, comprising combination chemotherapy +/- monoclonal antibodies, the oncological outcome-especially of the subgroup of patients with peritoneal metastases-is still unsatisfactory. In addition to systemic therapy, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are specific treatment options for a selected group of these patients and may provide an additional therapeutic benefit in the framework of an interdisciplinary treatment concept.
The COMBATAC trial is a prospective, multicenter, open-label, single-arm, single-stage phase II trial investigating perioperative systemic polychemotherapy including cetuximab in combination with CRS and HIPEC patients with histologically proven wild-type KRAS colorectal or appendiceal adenocarcinoma and synchronous or metachronous peritoneal carcinomatosis. The planned total number of patients to be recruited is 60. The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival (OS), perioperative morbidity and treatment-associated toxicity, feasibility of the combined treatment regimen, quality of life (QoL) and histopathological regression after preoperative chemotherapy.
The COMBATAC trial is designed to evaluate the feasibility and efficacy of the combined multidisciplinary treatment regimen consisting of perioperative systemic combination chemotherapy plus cetuximab and CRS plus bidirectional HIPEC with intraperitoneal oxaliplatin.
ClinicalTrials.gov Identifier: NCT01540344, EudraCT number: 2009-014040-11.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cachexia is a common problem in patients (pts) suffering from upper gastrointestinal cancer. In addition, most of these patients suffer from malabsorption and stenosis of the gastrointestinal tract ...due to their illness. Various methods of supplementary nutrition (enteral, parenteral) are practised. In patients with advanced pancreatic cancer (APC), phase angle, determined by bio-electrical impedance analysis (BIA), seems to be a survival predictor. The positive influence of BIA determinate predictors by additional nutrition is currently under discussion.
To examine the impact of additional parenteral nutrition (APN) we assessed outpatients suffering from APC and progressive cachexia. The assessment based on the BIA method. Assessment parameters were phase angle, ECM/BCM index (ratio of extracellular mass to body cell mass), and BMI (body mass index). Patients suffering from progressive weight loss in spite of additional enteral nutritional support were eligible for the study.
Median treatment duration in 32 pts was 18 8-35 weeks. Response evaluation showed a benefit in 27 pts (84%) in at least one parameter. 14 pts (43.7%) improved or stabilised in all three parameters. The median ECM/BCM index was 1.7 1.11-3.14 at start of APN and improved down to 1.5 1.12-3.36 during therapy. The median BMI increased from 19.7 14.4-25.9 to 20.5 15.4-25.0. The median phase angle improved by 10% from 3.6 2.3-5.1 to 3.9 2.2-5.1.
We demonstrated the positive impact of APN on the assessed parameters, first of all the phase angle, and we observed at least a temporary benefit or stabilisation of the nutritional status in the majority of the investigated patients. Based on these findings we are currently investigating the impact of APN on survival in a larger patient cohort.
ClinicalTrials.gov Identifier: NCT00919659.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A pooled analysis of three prospective trials of preoperative radiochemotherapy (RCT) for rectal cancer by using oxaliplatin and capecitabine with or without cetuximab was performed to evaluate the ...impact of additional cetuximab on pathologic complete response (pCR) rates and tumor regression (TRG) grades.
Of 202 patients, 172 patients met the inclusion criteria (primary tumor stage II/III, M0). All patients received concurrent RCT, and 46 patients received additional cetuximab therapy. A correlation of pretreatment clinicopathologic factors and cetuximab treatment with early pCR rates (TRG > 50%) was performed with univariate and multivariate analyses. Toxicity data were recorded for all patients.
Of 172 patients, 24 (14%) patients achieved a pCR, and 84 of 172 (71%) patients showed a TRG of >50% in the surgical specimen assessment after preoperative treatment. Age, gender, and T/N stages, as well as localization of the tumor, were not associated with pCR or good TRG. The pCR rate was 16% after preoperative RCT alone and 9% with concurrent cetuximab therapy (p = 0.32). A significantly reduced TRG of >50% was found after RCT with cetuximab compared to RCT alone (p = 0.0035). This was validated by a multivariate analysis with all available clinical factors (p = 0.0037). Acute toxicity and surgical complications were not increased with additional cetuximab.
Triple therapy with RCT and cetuximab seems to be feasible, with no unexpected toxicity. Early response assessment (TRG), however, suggests subadditive interaction. A longer follow-up (and finally randomized trials) is needed to draw any firm conclusions with respect to local and distant failure rates.
ABSTRACT
Sunitinib is a reference standard of care for the treatment of metastatic renal cell carcinoma (mRCC). While the tolerability of sunitinib is consistent across clinical studies, the impact ...of tolerability on clinical benefit necessitates effective therapy management, focusing on optimization of dosing, treatment duration, and management of adverse events. Managing individual tolerability concerns in clinical practice should include patient education and practical management strategies. We review the sunitinib tolerability profile in mRCC and describe practical strategies to manage adverse events in order to maximize clinical benefit. These strategies may allow long-term sunitinib treatment, thereby optimizing the available clinical efficacy.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Colorectal metastases still represent a challenge to all oncologists despite progresses achieved by improved resectability, systemic chemotherapy and targeted therapies. In particular in patients ...with oligo-metastases, the role of surgical resections has been redefined. Resection is the most effective treatment method for liver metastases performed with curative intent; however, primary rate of resectability is low. Several methods to increase resectability have been developed: conversion chemotherapy, portal vein embolization, two-stage resections, vascular reconstruction of the liver veins, combination of resection and intraoperative ablation. Liver resections can be performed at present with low mortality. Patients with isolated peritoneal metastases, no extra-abdominal disease, low volume tumor and complete surgical cytoreduction do benefit from surgery and hyperthermic intraperitoneal chemotherapy. Several national guidelines recommend multimodality treatment for highly selected patients. The management of stage IV colorectal cancer includes several disciplines with focus on resection. A multidisciplinary evaluation of all patients is of crucial importance to define the treatment sequence and individual strategies for each patient.
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