Breast-conserving therapy with partial or whole breast irradiation: Ten-year results of the Budapest randomized trial

Background and purpose

To report the long-term results of a single-institution randomized study comparing the results of breast-conserving treatment with partial breast irradiation (PBI) or conventional whole breast irradiation (WBI).

Patients and methods

Between 1998 and 2004, 258 selected women with pT1 pN0-1mi M0, grade 1–2, non-lobular breast cancer without the presence of extensive intraductal component and resected with negative margins were randomized after BCS to receive 50 Gy WBI (n = 130) or PBI (n = 128). The latter consisted of either 7 × 5.2 Gy high-dose-rate (HDR) multi-catheter brachytherapy (BT; n = 88) or 50 Gy electron beam (EB) irradiation (n = 40). Primary endpoint was local recurrence (LR) as a first event. Secondary endpoints were overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and cosmetic results.

Results

After a median follow up of 10.2 years, the ten-year actuarial rate of LR was 5.9% and 5.1% in PBI and WBI arms, respectively (p = 0.77). There was no significant difference in the ten-year probability of OS (80% vs 82%), CSS (94% vs 92%), and DFS (85% vs 84%), either. The rate of excellent-good cosmetic result was 81% in the PBI, and 63% in the control group (p < 0.01).

Conclusions

Partial breast irradiation delivered by interstitial HDR BT or EB for a selected group of early-stage breast cancer patients produces similar ten-year results to those achieved with conventional WBI. Significantly better cosmetic outcome can be achieved with HDR BT implants compared with the outcome after WBI.     

Interstitial hyperthermia and interstitial radiotherapy of a rat rhabdomyosarcoma; effects of sequential treatment and consequences for clonogenic repopulation

Animal tumour experiments have been performed to elucidate the interactions between interstitial hyperthermia (IHT) and interstitial radiotherapy (IRT), and to obtain information about the most effective sequence of these treatment modalities. Experimental tumours, transplanted in the flank of Wag/Rij rats, were treated with IHT for 0·5 h at 44°C, and with IRT using low dose-rate (LDR) iridium-192 sources. Both tumour cure probability and the fraction of clonogenic cells in vitro after different IHT and IRT treatments in vivo, were used as endpoints. The sequence of a short (0·5 h) IHT treatment followed by an extended LDR-IRT treatment lasting up to 10 days appeared to be very effective, and resulted in a significant thermal enhancement ratio of 1·34 at the 50% tumour cure probability level. A not significantly increased thermal enhancement of 1·06 was found when the same IHT treatment followed IRT. The level of clonogenic cell survival after IHT alone is high (0·24 ± 0·08) compared with that after an IRT dose of 20 Gy (0·017 ± 0·004). Clonogenic cell repopulation started 2–4 days after the in vivo treatment irrespective of the type of treatment. The in vivo combination of IHT and LDR-IRT resulted in lower surviving fractions compared with IRT alone, regardless of the time interval between the end of treatment and in vitro clonogenic assay. IHT followed by LDR-IRT appeared to be the most effective treatment in terms of tumour cure. The in vivo/in vitro studies indicated that the effect of hyperthermia is mainly attributed to radiosensitization, possibly by partial inhibition of sublethal damage repair processes during the subsequent irradiation. The hyperthermia-induced cytotoxicity was of minor importance as estimated from the surviving clonogenic fraction.     

Trajectory modulated prone breast irradiation: A LINAC-based technique combining intensity modulated delivery and motion of the couch

Purpose

External beam radiation therapy (EBRT) provides a non-invasive treatment alternative for accelerated partial breast irradiation (APBI), however, limitations in achievable dose conformity of current EBRT techniques have been correlated to reported toxicity. To enhance the conformity of EBRT APBI, a technique for conventional LINACs is developed, which through combined motion of the couch, intensity modulated delivery, and a prone breast setup, enables wide-angular coronal arc irradiation of the ipsilateral breast without irradiating through the thorax and contralateral breast.

Methods and materials

A couch trajectory optimization technique was developed to determine the trajectories that concurrently avoid collision with the LINAC and maintain the target within the MLC apertures. Inverse treatment planning was performed along the derived trajectory. The technique was experimentally implemented by programming the Varian TrueBeam™ STx in Developer Mode. The dosimetric accuracy of the delivery was evaluated by ion chamber and film measurements in phantom.

Results

The resulting optimized trajectory was shown to be necessarily non-isocentric, and contain both translation and rotations of the couch. Film measurements resulted in 93% of the points in the measured two-dimensional dose maps passing the 3%/3 mm Gamma criterion. Preliminary treatment plan comparison to 5-field 3D-conformal, IMRT, and VMAT demonstrated enhancement in conformity, and reduction of the normal tissue V_50% and V_100% parameters that have been correlated with EBRT toxicity.

Conclusions

The feasibility of wide-angular intensity modulated partial breast irradiation using motion of the couch has been demonstrated experimentally on a standard LINAC for the first time. For patients eligible for a prone setup, the technique may enable improvement of dose conformity and associated dose–volume parameters correlated with toxicity.     

Ductal carcinoma in situ: an overview

Advances in methods used to diagnose breast cancer have resulted in the increased detection of ductal carcinoma in situ; most of these are detected by screening mammograms and are confirmed by core needle biopsy. Currently, classification schemas are moving toward a molecular approach. Treatment options for patients with ductal carcinoma in situ are multiple and take into consideration end points such as local, regional or distant recurrence, overall survival and quality of life. Treatment methods continue to be controversial and debated in the oncology community. The quality of local control is multifactorial and depends on adequate surgical clearance, biological characteristics of the tumor, clinical presentation and the possibility of radiation therapies.     

Oral cancer: molecular technologies for risk assessment and diagnosis

Purpose: The effective biomarkers related to diagnosis, metastasis, drug resistance and irradiation sensitivity of oral cancers will help the pathologist and oncologist to determine the molecular taxonomy diagnosis and design the individualization treatment for the patients with oral cancers.     

Acute irradiation effects on morphology and function of rat submandibular glands

In this study the morphologic and functional changes were compared after irradiation (single dose, 15 Gy) of rat submandibular salivary glands. Before and 1-10 days after local irradiation of the gland region, samples of submandibular saliva were collected after stimulation by pilocarpine. At the same time-points and also 3 h postirradiation submandibular glands were carefully extirpated and prepared for histocytologic examination (LM, TEM). Maximal increase of the lag phase and decrease of the flow rate were observed 3 days after irradiation, while [K+] and [Na+] increased and decreased, respectively, from days 1 and 3 after irradiation. Morphologic changes were observed from the third hour after irradiation, were maximal 3 days after irradiation and had partially recovered by day 10. Three hours and 1 day after irradiation degranulation of convoluted granulated tubes (CGT) was observed. Three days after irradiation the most striking morphologic changes in serous and mucous cells were distension of the cisternae of the RER, degeneration of mitochondria and vacuolization of the cytoplasm. Fibril-like condensations of electron dense material in the mucous granules were observed 3 h, 1 and 6 days after irradiation. Regranulation of CGT cells was observed from day 6. From this study it is concluded that changes in salivary gland function can be observed before major morphologic changes occur. Functional changes persist after the morphologic changes seem to have virtually returned to normal.     

Subliminal ultraviolet-B irradiation for the prevention of vitamin D deficiency in the elderly: a feasibility study

AIM: To investigate whether daily subliminal ultraviolet-B irradiation in elderly subjects can maintain a normal vitamin D status. MATERIAL AND METHODS: In an open, uncontrolled study, 10 residents (four men and six women), mean age on entry of 83 years (range 65-97 years), from a residential nursing home in County Durham, England, were exposed daily to an artificial source of ultraviolet-B radiation equivalent to 15 min of summer sunshine. The change in plasma 25-hydroxyvitamin D levels following irradiation was measured. RESULTS: Improvement in the vitamin D status of the elderly residents was achieved with no change in their routine and with no intervention on the part of carers. CONCLUSIONS: On the basis of this small pilot study we conclude that subliminal ultraviolet-B irradiation may be effective in maintaining vitamin D status in elderly people at a lower cost than that of using oral vitamin D supplementation. Further controlled studies are needed before this technique can be recommended to change health policy with regard to the vitamin D status of institutionalised elderly people.     

Superoxide dismutase in epidermis: its relation to keratinocyte proliferation

Decreased superoxide dismutase (SOD) activity has been reported in various hyperproliferative tissues. In order to elucidate the significance of SOD activity in keratinocyte proliferation, we measured the SOD activity in several pathologic epidermal conditions. The SOD activity was significantly decreased in psoriatic hyperproliferative epidermis as well as in basal cell epithelioma, squamous cell carcinoma and seborrheic keratosis. Following tape stripping in vivo, pig epidermis revealed a marked increase in thymidine uptake and mitotic counts. The peak of the thymidine uptake was observed at 24 h, which was followed by the increased mitotic counts (peak at 48 h). The pig skin revealed a decreased epidermal SOD activity following the tape stripping. A decline of SOD activity was observed within 7 days after the tape stripping and about a 50% decrease was observed at 48 h. Epidermis is known to contain both Cu, Zn-SOD and Mn-SOD activities; the decreased SOD activity after tape stripping was mainly due to decreased Cu, Zn-SOD activity without any significant alteration of Mn-SOD activity. Following UVB irradiation (2MED) in vivo, pig epidermis revealed decreased thymidine incorporation as well as decreased mitotic counts. Epidermal SOD activity, however, was not altered by the UVBirradiation. Pig epidermis is also known to indicate decreased cell proliferative activity in the presence of various chemicals in vitro. These modalities, which include retinoid (Ro 10-1670), colchicine and protein synthesis inhibitors (puromycin, actinomycin D, cycloheximide), had no effect on the epidermal SOD activity. Our results indicate that, although the decreased SOD activity appears to be comcomitant with keratinocyte hyperproliferation, no alteration of SOD activity is observed in hypoproliferative epidermis. The significance of the altered SOD activity in the regulatory mechanism of keratinocyte proliferation remains unknown at present.     

An accumulation of glucosylceramide in the stratum corneum due to attenuated activity of beta-glucocerebrosidase is associated with the early phase of UVB-induced alteration in cutaneous barrier function

Epidermal glucosylceramide (GlcCer) metabolism is essential to the maintenance of skin homeostasis. Although exposure of the skin to ultraviolet (UV) radiation elicits dramatic physiological and biological changes in the epidermis attributable to barrier perturbation, wrinkle formation and inflammation, little is known about UV-induced changes in GlcCer metabolism. In this study, we have assessed β-glucocerebrosidase (GlcCer’ase) activity in murine epidermis before and after a single UVB irradiation and have compared it with GlcCer and ceramide (Cer) levels. GlcCer’ase enzymatic activity was significantly suppressed in a dose-dependent manner one day after UVB (70 mJ/cm²) irradiation despite a significant increase in GlcCer’ase mRNA. The marked decrease in enzyme activity was followed by an accumulation of GlcCer in the stratum corneum, which peaked at day 2. This decreased level of GlcCer’ase activity returned to 80% of the control level by day 3 followed by a return of GlcCer level to the control level by day 4. In the whole epidermis, significant increases in Cer and GlcCer levels occurred on day 3 and on day 2, respectively. These results suggest that UVB irradiation dramatically affects the metabolism of GlcCer to Cer in the epidermis (including the stratum corneum) and that this may be closely associated with the early and minor phase of UVB-induced alteration in cutaneous barrier function.