Purpose This study aimed to confirm the decision-making patterns for life-sustaining treatment (LST) and analyze medical service utilization changes after enforcement of the Life-Sustaining Treatment Decision-Making Act.
Materials and Methods Of 1,237 patients who completed legal forms for life-sustaining treatment (hereafter called the LST form) at three academic hospitals and died at the same institutions, 1,018 cancer patients were included. Medical service utilization and costs were analyzed using claims data.
Results The median time to death from completion of the LST form was three days (range, 0 to 248 days). Of these, 517 people died within two days of completing the document, and 36.1% of all patients prepared the LST form themselves. The frequency of use of the intensive care unit, continuous renal replacement therapy, and mechanical ventilation was significantly higher when the families filled out the form without knowing the patient’s intention. In the top 10% of the medical expense groups, the decision-makers for LST were family members rather than patients (28% patients vs. 32% family members who knew and 40% family members who did not know the patient’s intention).
Conclusion The cancer patient’s own decision-making rather than the family’s decision was associated with earlier decision-making, less use of some critical treatments (except chemotherapy) and expensive evaluations, and a trend toward lower medical costs.
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Purpose
Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a rare genetic syndrome resulting from germline mutations in fumarate hydratase. The combination of bevacizumab plus erlotinib showed promising interim results for HLRCC-associated RCC. Based on these results, we analyzed the outcome of bevacizumab plus erlotinib in Korean patients with HLRCC-associated RCC.
Materials and Methods
We retrospectively reviewed the efficacy and safety of bevacizumab plus erlotinib in patients with HLRCC-associated RCC who were confirmed to have germline mutations in fumarate hydratase. The primary endpoint was the objective response rate (ORR), while the secondary endpoints were progression-free survival (PFS) and overall survival (OS).
Result
We identified 10 patients with advanced HLRCC-associated RCC who received bevacizumab plus erlotinib. Median age at diagnosis was 41 years, and five of the patients had received the combination as first- or second-line treatments. The ORR was 50% and the median PFS and OS were 13.3 and 14.1 months, respectively. Most adverse events were predictable and manageable by conventional measures, except for one instance where a patient died of gastrointestinal bleeding.
Conclusion
This is the first real-world outcome of the treatment of advanced HLRCC-associated RCC. Bevacizumab plus erlotinib therapy showed promising activity with moderate toxicity. We should be increasingly aware of HLRCC-associated RCC and bevacizumab plus erlotinib should be a first-line treatment for this condition, unless other promising data are published.
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On the Shoulders of Giants: The Evolution of Renal Cell Carcinoma Treatment—Cytokines, Targeted Therapy, and Immunotherapy Janice P. Dutcher, Ronan Flippot, Jaleh Fallah, Bernard Escudier American Society of Clinical Oncology Educational Book.2020; (40): 418. CrossRef
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Purpose Cetuximab demonstrates improved efficacy outcomes in patients with metastatic colorectal cancer (mCRC) harboring wild-type KRAS exon 2. Resistance to cetuximab is mediated by activating less frequent mutations in the RAS genes beyond KRAS exon 2. We performed extended RASmutational analysis using a high -throughput genotyping platform (OncoMap) and evaluated extended RAS analysis for predicting cetuximab efficacy in patients harboring wild-type KRAS exon 2 tumors following Sanger sequencing.
Materials and Methods Extended RAS analysis was performed on 227 wild-type KRAS exon 2 mCRC patients who received cetuximab as salvage treatment using OncoMap ver. 4.0. Targeted genes included exon 2, exon 3, and exon 4, both in KRAS and NRAS, and included BRAF exon 15. We assessed efficacy by the new RAS mutation status.
Results The OncoMap detected 57 additional mutations (25.1%): 25 (11%) in KRAS exon 2 and 32 (14.1%) beyond KRAS exon 2. Survival differences were observed after dividing patients into the wild-type RAS group (n=170) and mutant RAS group (n=57) using OncoMap. Progression-free survival was 4.8 months versus 1.8 months (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.32 to 0.61), and overall survival was 11.9 months versus 8.4 months (HR, 0.65; 95% CI, 0.47 to 0.88).
Conclusion Sanger sequencing is not sufficient for selecting candidates for cetuximab treatment. High-throughput extended RAS genotyping is a feasible approach for this purpose and identifies patients who might benefit from cetuximab treatment.
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