Explore the vast range of titles available.

Background Metastatic colorectal cancer (mCRC) remains a lethal disease. Survival, however, is increasing due to a growing number of treatment options. Yet due to the number of prognostic factors and their interactions, prediction of mortality is difficult. The aim of this study is to provide a clinical model supporting prognostication of mCRC mortality in daily practice. Methods Data from 1104 patients with mCRC in three prospective cancer datasets were used to construct and validate Cox models. Input factors for stepwise backward method variable selection were sex, RAS/BRAF -status, microsatellite status, treatment type (no treatment, systemic treatment with or without resection of metastasis), tumor load, location of primary tumor, metastatic patterns and synchronous or metachronous disease. The final prognostic model for prediction of survival at two and 3 years was validated via bootstrapping to obtain calibration and discrimination C-indices and dynamic time dependent AUC. Results Age, sidedness, number of organs with metastases, lung as only site of metastasis, BRAF mutation status and treatment type were selected for the model. Treatment type had the most prominent influence on survival (resection of metastasis HR 0.26, CI 0.21–0.32; any treatment vs no treatment HR 0.31, CI 0.21–0.32), followed by BRAF mutational status (HR 2.58, CI 1.19–1.59). Validation showed high accuracy with C-indices of 72.2 and 71.4%, and dynamic time dependent AUC’s of 76.7 ± 1.53% (both at 2 or 3 years), respectively. Conclusion The mCRC mortality prediction model is well calibrated and internally valid. It has the potential to support both, clinical prognostication for treatment decisions and patient communication.

Biliary tract cancers are rare cancers with poor prognosis due to a lack of therapeutic options, especially after the failure of first-line systemic treatment. Targeted treatments for this clinical situation are promising and have entered clinical practice. We aimed to describe the overall survival of matched targeted treatment after first-line treatment in patients with biliary tract cancers in an Austrian real-world multicenter cohort. We performed a multicenter retrospective chart review of patients with biliary tract cancer between September 2015 and January 2022. Data, including comprehensive molecular characteristics—next generation sequencing (NGS) and immunohistochemistry (IHC), clinical history, surgical procedures, ablative treatments, patient history, and systemic chemotherapy, were extracted from the records of the participating institutions. Targeted treatment was matched according to the ESMO scale for the clinical actionability of molecular targets (ESCAT). We identified 159 patients with the available molecular characteristics. A total of 79 patients underwent second-line treatment. Of these, 36 patients received matched targeted treatment beyond the first-line and were compared with 43 patients treated with cytotoxic chemotherapy in terms of efficacy outcomes. For Tier I/II alterations, we observed a progression free survival ratio (PFS targeted /PFS pre-chemotherapy ) of 1.86, p = 0.059. The overall survival for patients receiving at least two lines of systemic treatment significantly favored the targeted approach, with an overall survival of 22.3 months (95% CI 14.7–29.3) vs. 17.5 months (95% CI 1.7–19.8; p = 0.048). Our results underscore the value of targeted treatment approaches based on extended molecular characterization of biliary tract cancer to improve clinical outcomes.

Background Safety and efficacy of immune checkpoint inhibitors in advanced gastric or gastroesophageal junction (GEJ) cancer could be demonstrated in predominantly Asian cohorts, whereas data in Western patients outside of clinical trials are vastly missing. Methods In this multi-institutional retrospective analysis conducted at nine oncologic centers in Austria, we tried to assess feasibility of checkpoint inhibitors in advanced gastric/GEJ cancer in a real-world Western cohort. Results In total, data from 50 patients with metastatic gastric/GEJ cancer who received nivolumab or pembrolizumab in a palliative setting between November 2015 and April 2020 have been evaluated. The median number of previous palliative therapy lines was two. The median progression-free survival (PFS) and overall survival (OS) were 2.1 (95% CI: 1.4 – 2.8) and 6.3 (95% CI: 3.3 – 9.3) months, respectively. There was no statistically significant difference in median OS according to microsatellite or PD-L1 status. However, a trend towards prolonged PFS and OS for the microsatellite instability high subgroup could be observed. Patients with an ECOG Performance Status (PS) ≥ 2 displayed a significantly worse outcome than those with an ECOG PS ≤ 1 ( p  = .03). Only one patient discontinued immunotherapy due to treatment-related toxicity. Conclusions Our results support feasibility of nivolumab and pembrolizumab in pre-treated patients with metastatic gastric and GEJ cancer in a Western real-world cohort. Further phase II/III studies are needed to confirm clinical efficacy.

Purpose: Cancer and its treatment strategies can have adverse effects on physical functioning and quality of life. Treatment strategies for better quality of life are still an unresolved issue. Physical activity is a promising treatment strategy that still has to be fully investigated. Methods: The ABCSG C07-EXERCISE study evaluated the feasibility of a 1-year exercise training after adjuvant chemotherapy in colorectal cancer patients. The present report presents the patient-reported outcomes during the exercise training. Fourteen patients of one center filled out the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C30) questionnaire at 5 time points after initiating a 1-year exercise training. Results: At baseline, patients scored social functioning, emotional functioning, financial impact, insomnia, and diarrhea much worse than the German general population. After 1 year of a structured exercise training, a large improvement was reported for social functioning; moderate improvements were reported for pain, diarrhea, financial impact, and taste; and a small change for physical and emotional functioning as well as for global quality of life. Conclusions: The present study observed improvements of social, physical, and emotional functioning as well as global quality of life after 1 year of a structured exercise training in patients with locally advanced colorectal cancer after receiving adjuvant chemotherapy. To enhance compliance, sufficient support and different sport facilities should be offered. The positive effect of exercise on patient-reported outcomes, disease-free survival, and overall survival in cancer survivors have to be further investigated in further randomized clinical trials.

Background In metastatic colorectal cancer (mCRC), the localization of the primary tumour has been shown to be of prognostic as well as predictive relevance. Methods With the aim to investigate clinical and molecular disease characteristics with respect to sidedness in a real-world cohort, we analyzed 161 mCRC patients included in the KRAS Registry of the Arbeitsgemeinschaft Medikamentöse Tumortherapie (AGMT) between January 2006 and October 2013. Results Right-sided mCRC displayed a worse median overall survival (OS) in comparison to left-sided disease (18.1 months [95%-CI: 14.3–40.7] versus 32.3 months [95%-CI: 25.5–38.6]; HR: 1.63 [95%-CI: 1.13–2.84]; p  = 0.013). The choice of the biological agent in front-line therapy had a statistically significant impact on median OS in patients with right-sided tumours (anti-epidermal growth factor receptor (EGFR): 10.6 months [95%-CI: 5.2-NA]; anti-vascular endothelial growth factor (VEGF): 26.2 months [95%-CI: 17.9-NA]; HR: 2.69 [95%-CI: 1.30–12.28]; p  = 0.015) but not in patients with left-sided tumours (anti-EGFR: 37.0 months [95%-CI: 20.2–56.6]; anti-VEGF: 32.3 months [95%-CI: 23.6–41.1]; HR: 0.97 [95%-CI: 0.56–1.66]; p  = 0.905). When evaluating molecular characteristics of tumour samples, we found a clinically meaningful trend towards an inferior OS in TP53 mutant mCRC treated with anti-EGFR based therapy compared to anti-VEGF based therapy (17.1 months [95%-CI: 8.7-NA] versus 38.3 months [95%-CI: 23.6–48.0], HR = 1.95 [95%-CI: 0.95–5.88]; p  = 0.066), which was not significantly dependent on sidedness. This was not the case in patients with TP53 wild-type tumours. Therefore we evaluated the combined impact of sidedness and TP53 mutation status in the anti-EGFR treated cohort and patients with left-sided/TP53 wild-type mCRC showed the longest median OS (38.9 months) of all groups (right-sided/TP53 mutant: 12.1 months; right-sided/TP53 wild-type: 8.9 months; left-sided/TP53 mutant: 18.4 months; p  = 0.020). Conclusions TP53 mutation and right-sidedness are associated with shorter OS in patients treated with anti-EGFR based therapy but not with anti-VEGF based therapy. The confirmation of the predictive value of TP53 mutation status in a larger cohort is warranted.

Background Palliative chemotherapy in patients with nonresectable advanced colorectal carcinoma is performed to prolong survival, alleviate tumor-associated symptoms, and maintain or improve health-related quality of life (HRQOL). In this prospective single-center observational study, we assessed HRQOL across the various lines of palliative chemotherapy. Methods HRQOL data were acquired using the EORTC Quality of Life Questionnaire-C30 (QLQ-C30) questionnaire. The first assessment was performed at the beginning of each chemotherapy line, the second after three cycles, and the third at the end of chemotherapy. Further assessments were conducted during checkups every 3 months in our outpatient unit. Results In total, 100 consecutive patients with colorectal carcinoma (mean age 66.4 years; 60 % men) treated with palliative chemotherapy were recruited. Generally, QOL deteriorated constantly across time. Physical functioning, fatigue, pain, dyspnea, and appetite worsened steadily from first-line chemotherapy to the later treatment phase. Global QOL, emotional functioning, and role functioning improved slightly after the end of first-line chemotherapy, deteriorated during second-line chemotherapy to the level of first-line chemotherapy, and further deteriorated in the later treatment phases. In additional analyses, we found the largest differences between patients with and without a treatment response for pain (19.0 vs. 37.2 points) and appetite loss (17.4 vs. 32.7 points). Conclusion The individual QOL domains deteriorated constantly across time. Our data indicate that patients undergoing first- and second-line palliative chemotherapy experience stabilization of global QOL and psychosocial symptoms. We also found that unselected patients who achieved a treatment response had a lower symptom burden and better QOL than did patients with progressive disease.

In 2007, the ASSO-LM1 trial, a multicenter prospective study, was initiated to investigate the resectability (R0) rate following preoperative combination therapy with XELOX and bevacizumab in patients with potentially resectable colorectal liver metastases. Six cycles of systemic therapy were administered preoperatively, although the sixth cycle did not include bevacizumab, resulting in 5 weeks between the last bevacizumab dose and surgery. Treatment with bevacizumab plus XELOX was restarted for another six cycles postoperatively. In total, 43 patients were enrolled in the ASSO-LM1 trial. Eight patients were ineligible for resection due to protocol violation and progression in two patients. The resectability of operated patients was 97% with 34 R0 resections and one R1 resection. Postoperative morbidity occurred in 22% of patients, of which three operative revisions were related to the primary tumor resection. Efficacy results for response in 38 eligible patients confirmed an ORR of 66%, 31% SD and 3% PD according to RECIST. Preoperative grade 3/4 adverse events were 17% diarrhea, 5% HFS and 5% thromboembolic events. Overall survival significantly differed depending upon the fulfillment of adjuvant treatment in curative resected patients (59.1 mo vs. 30.8 mo). In conclusion, the ASSO-LM1 trial is a hypothesis-generating study confirming the prognostic benefits of perioperative therapy with XELOX and bevacizumab in patients with metastatic colorectal cancer confined to the liver.

Current National Comprehensive Cancer Network (NCCN) and European Society of Medical Oncology (ESMO) guidelines recommend regorafenib or trifluridine/tipiracil (TAS-102) for the third-line therapy of metastatic colorectal cancer (mCRC). In this analysis, we evaluated hospitalizations during regorafenib or TAS-102 treatment and the impact of hospitalizations on overall survival (OS). This retrospective analysis was based on unselected, consecutive mCRC patients treated with regorafenib and/or TAS-102 at the tertiary cancer centers in Salzburg and Wels-Grieskirchen, Austria. Between January 2013 and May 2019, 93 patients started third- or fourth-line therapy with regorafenib or TAS-102. Tumor therapy (regorafenib versus TAS-102, HR: 1.95 [95% CI: 1.07–3.54], p = 0.03) and the Eastern Cooperative Oncology Group (ECOG) performance status (2–3 versus 0–1, HR: 4.04 [95% CI: 2.11–7.71], p < 0.001) showed a statistically significant association with hospitalization risk in multivariate analysis. The corresponding hospitalization probability from initiation of third- or fourth-line was 30% with regorafenib versus 18% with TAS-102 at five weeks and 41% versus 28% at ten weeks, respectively. Hospitalizations irrespective of cause during regorafenib or TAS-102 therapy did neither impact median survival in patients undergoing only third-line therapy (never-hospitalized: 5.7 months [95% CI: 3.9–10.5] versus hospitalized: 5.4 months [95% CI: 2.8–9.6], p = 0.45), nor in patients receiving third- and fourth-line therapy (12.2 months [95% CI: 10.6–28.8] versus 18.6 months [95% CI: 6.3-not reached], p = 0.90). In conclusion, apart from poor ECOG performance status, regorafenib therapy was associated with an increased hospitalization probability during palliative systemic third- and fourth-line therapy in mCRC. However, hospitalizations during regorafenib or TAS-102 therapy did not impact OS beyond second-line therapy.

We aimed to investigate the effectiveness of oncological treatments in metastatic CRC related to comorbidities and age. This retrospective study included 1105 patients from three oncological centers. aaCCI and CCI was available from 577 patients. An aaCCI > 3 was of the highest predictive value compared to other aaCCI-levels, CCI or age (p < 0.001 for all). Treatment (best supportive care (BSC), systemic treatment only (STO) and resection of metastases (ROM)) significantly prolonged survival in patients with aaCCI > 3 (STO: HR 0.39, CI 0.29–0.51; ROM: HR 0.16, CI 0.10–0.24) and patients older than 70 years (STO: HR 0.56, CI 0.47–0.66; ROM: HR 0.23, 0.18–0.30). Median overall survival was shorter in patients with aaCCI or age > 70 years and interaction for treatment type not significant for aaCCI, but significant for age older or younger than 70 years (STO: p = 0.01; ROM p = 0.02). BSC is more often considered as optimal care for patients with an aaCCI > 3 (37.6% vs. 12.4%; p < 0.001) or age > 70 years (35.7% vs. 11.2%; p < 0.001). Older patients or patients with comorbidities benefit from cancer-specific therapy independently of their age and comorbidities.

IntroductionDespite advances in adjuvant chemotherapy, 20–30% of patients in stages II–III colorectal cancer will eventually relapse. Observational studies showed a reduction in relapse rate, colon cancer-specific mortality, and overall mortality by physical activity. Results from prospective randomized interventional studies to confirm these observational data are lacking. The aims of this prospective single-arm multicenter pilot study are to evaluate feasibility and safety of exercise training after adjuvant chemotherapy in colorectal cancer patients.Patients and methodsThe training was performed three times per week for 1 year and was increased gradually in three phases until reaching 18 metabolic equivalent task hours per week.ResultsOverall, 30 patients were included. The planned training intensity could be achieved in all three phases. Patients experienced a performance increase of median 35.5 watt, a weight-loss of a median of 3.0 kg, and a reduction in body fat content of median 1.0% during this exercise training. The analysis showed early study termination due to non-compliance in 10/30 patients (33.3%), disease progression in 4 patients (13.3%), and serious adverse events in 2 patients (6.7%). About half of patients (46.7%) completed the pilot study as planned. Biomarker analysis from 20 patients showed a non-significant reduction in insulin-like growth factor 1 (IGF-1), insulin-like growth factor 2 (IGF-2) and insulin-like growth factor binding protein 3 (IGF-BP3) levels, significant increases in adiponectin and leptin levels, and a non-significant increase in C-peptide levels.ConclusionExercise training is feasible in patients with colorectal cancer after completion of adjuvant chemotherapy. The main problem encountered during the study was compliance. To improve compliance of exercise training, several measures were adapted for the upcoming prospective randomized ABCSG C08 Exercise II study.