SBRT for central lung tumors seems to be safe, although treatment of larger tumors does carry an increased risk of high-grade toxicity. Efforts to decrease the toxicity risk by decreasing the biologically equivalent dose resulted in increased local failure.
Accumulating evidence suggests that many cancers, including BRCA1- and BRCA2-associated breast cancers, are deficient in DNA repair processes. Both hereditary and sporadic breast cancers have been found to have significant downregulation of repair factors. This has provided opportunities to exploit DNA repair deficiencies, whether acquired or inherited. Here, we review efforts to exploit DNA repair deficiencies in tumors, with a focus on breast cancer. A variety of agents, including PARP (poly [ADP-ribose] polymerase) inhibitors, are currently under investigation in clinical trials and available results will be reviewed.
Objective(s)
(a) To prospectively determine if multidwell position dose delivery can decrease skin dose and resultant toxicity over single dwell balloon-catheter partial breast irradiation, and (b) to evaluate whether specific skin parameters could be safely used instead of skin-balloon distance alone for predicting toxicity and treatment eligibility.
Methods
A single-arm phase II study using a Simon two-stage design was performed on 28 women with stage 0-II breast cancer. All patients were treated with multiple dwell position balloon-catheter brachytherapy. The primary endpoint was ≥ grade 2 skin toxicity. Initial entry required a balloon-skin distance ≥ 7 mm. Based on the toxicity in the first 16 patients, additional patients were treated irrespective of skin-balloon distance as long as the Dmax to 1 mm skin thickness was < 130%.
Results
Compared to the phantom single dwell plans, multidwell planning yielded superior PTV coverage as per median V90, V95 and V100, but had slightly worse V150, V200 and DHI. Dmax to skin was decreased by multidwell planning at multiple skin thicknesses. The most common acute toxicity was grade 1 erythema (57%), and only two patients (7%) developed acute grade 2 toxicity (erythema). Late grade 1 fibrosis was seen in 32%. No patients experienced grade 3, 4, or 5 toxicity.
Conclusions
Multidwell position planning for balloon-catheter brachytherapy results in lower skin doses with equal to superior PTV coverage and an overall low rate of initial skin toxicity. Our data suggest that limiting the Dmax to < 130% to 1 mm thick skin is achievable and results in minimal toxicity.
Breast conservation therapy (BCT), consisting of local excision of the breast tumor to achieve negative margins followed by whole breast irradiation, is standard treatment for early-stage breast cancer. The conventional radiotherapy course treats the entire breast, typically followed by a boost to the tumor bed over six to seven weeks. While the efficacy and cosmetic outcomes of conventionally fractionated whole breast radiation are well-established, two strategies are being investigated to address the lengthy treatment time associated with adjuvant radiotherapy for early-stage breast cancer. Accelerated partial breast irradiation (APBI) involves treatment to the tumor bed plus a small margin, allowing completion of therapy in five days or less. A variety of techniques, each with unique advantages and disadvantages, is currently under investigation for delivering APBI. Hypofractionated whole breast radiation (hWBRT) involves treating the entire breast with larger daily doses of radiation over three to four weeks. This article reviews the principles behind APBI and hWBRT, the indications for each technique, and relevant data supporting their use.
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