Neoadjuvant chemotherapy for adult soft tissue sarcoma: comparaison of systemic and intra-arterial chemotherapy

Background

The introduction of a combined-modality approach, which added chemotherapy to local therapy (surgery and radiotherapy), has been controversial. We present our experience of the efficacy of neoadjuvant chemotherapy in patients with high-risk sarcomas and evaluate the benefit of intra-arterial (IA) chemotherapy.

Patients and methods

Forty patients with intermediate to high-grade soft tissue sarcomas (STS) were treated with neoadjuvant chemotherapy from 1994 to 2001 at the Institut Curie. Thirty-seven patients had localized tumours. Neoadjuvant intravenous (IV) chemotherapy consisted of 4–6 cycles of treatment (mainly CYVADIC, MAID). Sixteen patients (40%) received 2 cycles of IA chemotherapy with a combination of adriamycin and cisplatin. Radiotherapy was delivered in an adjuvant setting.

Results

All patients underwent limb-sparing surgical resection after neoadjuvant therapy and pathologic assessment of tumour necrosis was performed on the resected specimens. Two groups of tumours were analysed: 1–95% (28 cases), and 95–100% (10 cases) of pathological necrosis, with a survival benefit in the group with more than 95% necrosis (p = 0.07). IA chemotherapy was superior to IV chemotherapy in terms of the necrosis rate (p = 0.045). With a median follow-up of 51 months, the 2-year overall survival rate was 90% for localized tumours.

Conclusion

Neoadjuvant chemotherapy can be considered to be effective in the treatment of STS. This study demonstrates the benefit of neoadjuvant therapy for patients with a high necrosis rate (very clear tendency) and the contribution of IA chemotherapy to the response rate, but with no survival advantage.     

A two-stage hepatectomy procedure combined with portal vein embolization to achieve curative resection for initially unresectable multiple and bilobar colorectal liver metastases

OBJECTIVE: To assess outcome after a 2-stage hepatectomy procedure (TSHP) combined with portal vein embolization (PVE) in the treatment of patients with unresectable multiple and bilobar colorectal liver metastases (MBCLM). BACKGROUND: Patients with MBCLM are often considered for palliative chemotherapy only, due to too small future remnant liver (FRL). Recently, right hepatectomy with simultaneous left liver wedge resections after previous right PVE has been reported in a curative intent. However, the growth of metastatic nodules in FRL after PVE can be more rapid than that of the nontumoral remnant hepatic parenchyma. Therefore, metastases located in the FRL should be ideally resected before PVE. Then, a right (or extended right) hepatectomy can be safely performed during a second-stage hepatectomy. Therefore, we analyzed our experience with the use of TSHP combined with PVE in treatment of MBCLM. PATIENTS AND METHODS: Between December 1996 and April 2003, 33 patients with unresectable MBCLM were selected for a TSHP. A right or an extended right hepatectomy was planned after treatment of left FRL metastases to achieve a curative resection. The first-stage hepatectomy consisted in a clearance of the left hemiliver by resection or radiofrequency destruction of metastases of the left FRL. Subsequently, a right PVE was performed to induce atrophy of the right hemiliver and hypertrophy of the left hemiliver. Finally, a second-stage hepatectomy was planned to resect the right liver metastases. RESULTS: There was no operative mortality. Post-PVE morbidity was 18.1%; postoperative morbidity was 15.1% and 56.0% after first- and second-stage hepatectomy, respectively. TSHP could be achieved in 25 of 33 patients (75.7%). The 1- and 3-year survival rates were 70.0% and 54.4%, respectively, in the 25 patients in whom the TSHP was completed. CONCLUSIONS: In selected patients with initially unresectable MBCLM, a TSHP combined with PVE can be achieved safely with long-term survival similar to that observed in patients with initially resectable liver metastases.     

Assessing the role of nocturnal core body temperature dysregulation as a biomarker of neurodegeneration

The vast majority of patients with idiopathic rapid eye movement sleep behaviour disorder will develop a neurodegenerative α‐synuclein‐related condition, such as Parkinson’s disease or dementia with Lewy bodies. The pathology underlying dream enactment overlaps anatomically with the brainstem regions that regulate circadian core body temperature. Previously, nocturnal core body temperature regulation has been shown to be impaired in Parkinson’s disease. However, no study to date has investigated nocturnal core body temperature changes in patients with idiopathic rapid eye movement sleep behaviour disorder, which may prove to be an early objective biomarker for α‐synucleinopathies. Ten healthy controls, 15 patients with idiopathic rapid eye movement sleep behaviour disorder, 31 patients with Parkinson’s disease and six patients with dementia with Lewy bodies underwent clinical assessment and nocturnal polysomnography with core body temperature monitoring. A validated cosinor method was utilised for core body temperature analysis. No differences in mesor, nadir or time of nadir were observed between groups. However, when compared with healthy controls, the amplitude of the nocturnal core body temperature (mesor minus nadir) was significantly reduced in patients with idiopathic rapid eye movement sleep behaviour disorder, Parkinson’s disease with concurrent rapid eye movement sleep behaviour disorder and dementia with Lewy bodies (p < 0.001, p = 0.043 and p = 0.017, respectively). Importantly, this relationship was not seen in those patients with Parkinson’s disease without rapid eye movement sleep behaviour disorder. In addition, there was a significant negative correlation between amplitude of the core body temperature and self‐reported rapid eye movement sleep behaviour disorder symptoms. Changes in thermoregulatory circadian rhythm may be specifically associated with the pathology underlying rapid eye movement sleep behaviour disorder rather than simply that of α‐synucleinopathy. These findings implicate thermoregulatory dysfunction as a potential early biomarker for development of rapid eye movement sleep behaviour disorder‐associated neurodegeneration, and suggest that subpopulations with differing pathological underpinnings might exist in Parkinson’s disease.