In vitro Applications of the Terpene Mini-Path 2.0.

In 2019 four groups reported independently the development of a simplified enzymatic access to the diphosphates (IPP and DMAPP) of isopentenol and dimethylallyl alcohol (IOH and DMAOH). The former are the two universal precursors of all terpenes. We report here on an improved version of what we call the terpene mini-path as well as its use in enzymatic cascades in combination with various transferases. The goal of this study is to demonstrate the in vitro utility of the TMP in, i) synthesizing various natural terpenes, ii) revealing the product selectivity of an unknown terpene synthase, or iii) generating unnatural cyclobutylated terpenes.

IMRT or conformal radiotherapy for adjuvant treatment of retroperitoneal sarcoma?

PURPOSE: To compare the dose distribution between three-dimensional conformal radiotherapy (3DCRT), intensity modulated radiotherapy (IMRT) with six coplanar beams (6b-IMRT) and IMRT with nine coplanar beams (9b-IMRT) during adjuvant radiotherapy for retroperitoneal sarcoma. METHODS AND MATERIALS: The 10 most recent patients who had received adjuvant radiotherapy were reviewed. Three different treatment plans were generated (3DCRT, 6b-IMRT and 9b-IMRT) to deliver 50.4 Gy in 28 fractions. The dose delivered to the organs at risk (intestinal cavity (IC), contra- and ipsilateral kidney, liver, stomach and whole body), and the conformity index (CI) were compared. RESULTS: The integral dose to the intestinal cavity was similar with the three modalities but the dose distribution was different, with a change-over around 25 Gy: the V50 and the V40 were reduced five- and twofold, respectively, with IMRT compared to 3DCRT, and the V20 was increased by about 25% with IMRT. A similar integral dose was delivered to the whole body with the three modalities. The treated volume (V95 body) was approximately halved with IMRT compared to 3DCRT, and the CI was twice as good with IMRT than with 3DCRT. As expected, the V5 (body) was higher with IMRT compared to 3DCRT (p<0.0001) (a 12% increase with 6b-IMRT and a 21% increase with 9b-IMRT). Compared to 3DCRT, the mean dose delivered to the contralateral kidney increased from 1.5 to 4-4.4 Gy with IMRT. The number of monitor units was increased with IMRT, especially when nine beams were used instead of six. CONCLUSIONS: As expected, IMRT greatly reduced the high-dose irradiated volume and increased the low-dose exposure of the intestinal cavity, with a change-over around 25 Gy, compared to 3DCRT. The conformity index was compellingly better with IMRT. The integral dose delivered to the whole body was conserved with both 3DCRT and IMRT. Longer follow-up is needed to assess late toxicities to the small bowel, contralateral kidney and the risk of second cancers.

Reirradiation in head and neck cancers.

Salvage surgery is the mainstay of treatment for recurrences or secondary primary tumors in areas that were irradiated earlier. However, locoregional recurrence remains the main cause of death after surgery. Adjuvant reirradiation dramatically reduces locoregional recurrences but the risk-benefit ratio seems to be advantageous mostly for residual microscopic disease. In contrast, the rate of distant metastasis among reirradiated patients indicates that the local treatment alone is not sufficient. Full-dose exclusive chemo-reirradiation (over 60 Gy) can cure a subset of patients when surgery is not feasible. However, reirradiation is associated with a significant rate of severe toxicity and should, therefore, be compared with chemotherapy in randomized trials. Accrual may be difficult because of selection biases such as tumor volume, small volumes (largest axis less than 3-4 cm) being more likely to be irradiated. In addition, patients in poor general condition with severe comorbidities, organ dysfunction, or incomplete healing after salvage surgery, are unlikely to benefit from reirradiation. Noteworthy volumes to be reirradiated must be established between the head and neck surgeon and the radiation oncologist: the definition of the clinical target volume should be taken into account, the natural history of recurrent tumors, especially with regard to extension modalities, and the absence of strict correlation between imaging and histological real extension. This is even more critical with the advent of new irradiation techniques. Chemotherapy associations and new radiosensitizing agents are also under investigation. Comparison between reirradiation modalities is difficult because most trials are phase 2 mono-institutional trials. As selection of patients is a key issue, only phase 3 multiinstitutional trials can provide definitive results.