Osteosarcoma is a rare bone tumor that occurs in young adults with a subsequent peak in the fifth decade. Neoadjuvant and adjuvant chemotherapy and surgery cure approximately 60% of patients with l...

The aim of this study was to compare the results in terms of histologic response to primary chemotherapy of two sequential studies in osteosarcoma patients preoperatively treated with methotrexate, doxorubicin, cisplatin, and ifosfamide, given at different doses. Between January 1993 and March 1995, 171 patients with osteosarcoma of the extremity were treated according to a protocol of neoadjuvant chemotherapy with preoperative methotrexate, cisplatin, doxorubicin, and ifosfamide. From April 1995 to December 1999, 196 osteosarcoma patients were preoperatively treated with the same drugs at higher doses. Postoperatively, patients received the same treatment in both studies used, but poor responders (tumor necrosis <95%) had more cycles of treatment than good responders. Comparing the two chemotherapy regimens, there were no significant differences in terms of good histologic response to chemotherapy (69% vs. 62%), 5-year event-free survival (60% vs. 65%), 5-year overall survival (74% vs. 80%), and rate of local recurrence (6% vs. 4%). The 5-year event-free survival was significantly related to the serum level of alkaline phosphatase before treatment (77% for patients with normal values vs. 46% for patients with high values) and the degree of histologic response to preoperative chemotherapy (69% for good responders vs. 54% for poor responders). Increasing the doses of preoperative chemotherapy does not improve the rate of good histologic response and survival in osteosarcoma of the extremity. The degree of necrosis induced by preoperative treatment probably reflects an innate sensitivity to chemotherapy, which is not altered by increasing drug doses.

Background: The evidence on high-dose ifosfamide (HD-IFO) use in patients with relapsed osteosarcoma is limited. We performed a retrospective study to analyze HD-IFO activity. Methods: Patients with osteosarcoma relapsed after standard treatment [methotrexate, doxorubicin, cisplatin +/− ifosfamide (MAP+/−I)] with measurable disease according to RECIST1.1 were eligible to ifosfamide (3 g/m²/day) continuous infusion (c.i.) days 1–5 q21d. RECIST1.1 overall response rate (ORR) (complete response (CR) + partial response (PR)), progression-free survival at 6-month (6m-PFS), duration of response (DOR), and 2-year overall survival (2y-OS) were assessed. PARP1 expression and gene mutations were tested by immunohistochemistry and next-generation sequencing. Results: 51 patients were included. ORR was 20% (1 CR + 9 PR). Median DOR was 5 months (95%CI 2–7). Median PFS, 6m-PFS, OS, and 2y-OS were 6 months (95%CI 4–9), 51%, 15 months (10–19), and 30%, respectively. A second surgical complete remission (CR2) was achieved in 26 (51%) patients. After multivariate analysis, previous use of ifosfamide (HR 2.007, p = 0.034) and CR2 (HR 0.126, p < 0.001) showed a significant correlation with PFS and OS, respectively. No significant correlation was found between outcomes and PARP1 or gene mutations. Conclusions: HD-IFO should be considered as the standard first-line treatment option in relapsed osteosarcoma and control arm of future trial in this setting.

The role of chemotherapy for patients with dedifferentiated chondrosarcoma (DDCS) is still under discussion. Here, we present the outcome in patients with DDCS treated with intensive chemotherapy from the EUROpean Bone Over 40 Sarcoma Study. The chemotherapy regimen included doxorubicin, ifosfamide and cisplatin. Postoperative methotrexate was added in case of poor histological response. Toxicity was graded based on the National Cancer Institute expanded common toxicity criteria, version 2.0, and survival was analysed using Kaplan-Meier curves, log-rank tests and univariate Cox regression models. Fifty-seven patients with DDCS (localised, 34 [60%]; metastatic, 23 [40%]) aged 42-65 years were included. Surgical complete remission (SCR) was achieved in 36 (63%) patients. The median overall survival (OS) was 24 months (95% confidence interval, 22-25), and the 5-year OS was 39%. Patients with extremity localisation had a 5-year OS of 49% compared with 29% in patients with a central tumour (P = 0.08). Patients with localised disease had a 5-year OS of 46%, whereas patients with metastatic disease had a 5-year OS of 29% (P = 0.12). Patients in SCR had a 5-year OS of 49%, whereas patients not in SCR had a 5-year OS of 23% (P = 0.004). Chemotherapy toxicity was considerable but manageable. There was no treatment-related death, and 39 (70%) patients received ≥6 cycles of the planned nine chemotherapy cycles. Adding intensive chemotherapy to surgery for treatment of DDCS is feasible and shows favourable survival data compared with previous reports. With the limitations of data from a non-controlled trial, we conclude that chemotherapy could be considered in the management of patients aged >40 years.

Palliative sedation involves the use of sedative medication to relieve refractory symptoms in patients by reducing their level of consciousness. Although it is considered an acceptable clinical practice from most ethical points of view, palliative sedation is still a widely debated procedure and merits better understanding. The relevant medical literature pertaining to palliative sedation was analyzed and reviewed from various technical, relational, and bioethical perspectives. Proportionate palliative sedation is considered to be the most clinically appropriate modality for performing palliative sedation. However, guidelines must be followed to ensure that it is performed correctly. Benzodiazepines represent the first therapeutic option and careful monitoring of dosages is essential to avoid oversedation or undersedation. Proportionate palliative sedation is used to manage and relieve refractory symptoms in patients with cancer during their last days or hours of life. Evidence suggests that its use has no detrimental effect on survival. A different decision-making process is used to manage the withdrawal of hydration than the process used to determine whether proportionate palliative sedation is appropriate. Communication between patients, their relatives, and the health care staff is important during this medical intervention.