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A photoinduced nickel-catalyzed reductive carbonylative coupling from organohalides and N-(acyloxy)phthalimide esters with phenyl formate as the carbonyl source has been developed. This reaction could perform smoothly under mild conditions, and a series of aryl–alkyl and alkyl–alkyl unsymmetrical ketones were produced without the need of stoichiometric metal reductants. Mechanistic studies indicate that this reaction was initiated from radical capture by Ni(I)-carbonyl species and subsequent rapid carbonyl insertion.

Currently, most intensity-modulated radiation therapy systems use dose–volume (DV)-based objectives. Although acceptable plans can be generated using these objectives, much trial and error is necessary to plan complex cases with many structures because numerous parameters need to be adjusted. An objective function that makes use of a generalized equivalent uniform dose (gEUD) was developed recently that has the advantage of involving simple formulae and fewer parameters. In addition, not only does the gEUD-based optimization provide the same coverage of the target, it provides significantly better protection of critical structures. However, gEUD-based optimization may not be superior once dose distributions and dose–volume histograms (DVHs) are used to evaluate the plan. Moreover, it is difficult to fine-tune the DVH with gEUD-based optimization. In this paper, we propose a method for combining the gEUD-based and DV-based optimization approaches to overcome these limitations. In this method, the gEUD optimization is performed initially to search for a solution that meets or exceeds most of the treatment objectives. Depending on the requirements, DV-based optimization with a gradient technique is then used to fine-tune the DVHs. The DV constraints are specified according to the gEUD plan, and the initial intensities are obtained from the gEUD plan as well. We demonstrated this technique in two clinical cases: a prostate cancer and a head and neck cancer case. Compared with the DV-optimized plan, the gEUD plan provided better protection of critical structures and the target coverage was similar. However, homogeneities were slightly poorer. The gEUD plan was then fine-tuned with DV constraints, and the resulting plan was superior to the other plans in terms of the dose distributions. The planning time was significantly reduced as well. This technique is an effective means of optimizing individualized treatment plans.