Radiotherapy For Early Breast Cancer Research Articles

Cosmetic outcome 1, 2, 3, and 4 years after intraoperative radiotherapy or external beam radiotherapy for early breast cancer: An objective assessment of patients from a randomized controlled trial.

Cosmetic outcome 1, 2, 3, and 4 years after intraoperative radiotherapy or external beam radiotherapy for early breast cancer: An objective assessment of patients from a randomized controlled trial.

Gene expression profiling of human dermal fibroblasts exposed to bleomycin sulphate does not differentiate between radiation sensitive and control patients

BackgroundGene expression profiling of the transcriptional response of human dermal fibroblasts to in vitro radiation has shown promise as a predictive test of radiosensitivity. This study tested if treatment with the radiomimetic drug bleomycin sulphate could be used to differentiate radiation sensitive patients and controls in patients who had previously received radiotherapy for early breast cancer.FindingsEight patients who developed marked late radiation change assessed by photographic breast appearance and 8 matched patients without any change were selected from women entered in a prospective randomised trial of breast radiotherapy fractionation. Gene expression profiling of primary skin fibroblasts exposed in vitro to bleomycin sulphate and mock treated fibroblast controls was performed. 973 genes were up-regulated and 923 down-reguated in bleomycin sulphate treated compared to mock treated control fibroblasts. Gene ontology analysis revealed enriched groups were cellular localisation, apoptosis, cell cycle and DNA damage response for the deregulated genes. No transcriptional differences were identified between fibroblasts from radiation sensitive cases and control patients; subgroup analysis using cases exhibiting severe radiation sensitivity or with high risk alleles present in TGF β1 also showed no difference.ConclusionsThe transcriptional response of human dermal fibroblasts to bleomycin sulphate has been characterised. No differences between clinically radiation sensitive and control patients were detected using this approach.

P264 Intraoperative radiotherapy in early breast cancer – a single institution experience

P264 Intraoperative radiotherapy in early breast cancer – a single institution experience

P265 Cosmetic outcome one, two, three and four years after intra-operative radiotherapy compared with external beam radiotherapy for early breast cancer: an objective assessment of patients from a randomised controlled trial

P265 Cosmetic outcome one, two, three and four years after intra-operative radiotherapy compared with external beam radiotherapy for early breast cancer: an objective assessment of patients from a randomised controlled trial

Randomized Controlled Trial of Forward-Planned Intensity Modulated Radiotherapy for Early Breast Cancer: Interim Results at 2 Years

This single-center randomized trial was designed to investigate whether intensity-modulated radiotherapy (IMRT) reduces late toxicity in patients with early-stage breast cancer. The standard tangential plans of 1,145 nonselected patients were analyzed. The patients with inhomogeneous plans were randomized to a simple method of forward-planned IMRT or standard radiotherapy (RT). The primary endpoint was serial photographic assessment of breast shrinkage. At 2 years, no significant difference was found in the development of any photographically assessed breast shrinkage between the patients randomized to the interventional or control group (odds ratio, 1.51; 95% confidence interval, 0.83-1.58; p = .41). The patients in the control group were more likely to develop telangiectasia than those in the IMRT group (odds ratio, 1.68; 95% confidence interval 1.13-2.40; p = .009). Poor baseline surgical cosmesis resulted in poor overall cosmesis at 2 years after RT. In patients who had good surgical cosmesis, those randomized to IMRT were less likely to deteriorate to a moderate or poor overall cosmesis than those in the control group (odds ratio, 0.63; 95% confidence interval, 0.39-1.03, p = .061). IMRT can lead to a significant reduction in telangiectasia at comparatively early follow-up of only 2 years after RT completion. An important component of breast induration and shrinkage will actually result from the surgery and not from the RT. Surgical cosmesis is an important determinant of overall cosmesis and could partially mask the longer term benefits of IMRT at this early stage.

Treatments to die for

It turns out that there are a few anecdotes of deaths from acupuncture administered by poorly trained therapists in Asia, but none in Britain. So we have to be frightened that we might die from acupuncture?1 And is orthodox medicine blameless? The Department of Health itself estimates that there are ‘some 850,000 adverse events in the NHS every year … resulting in additional costs in excess of £2 billion annually’.2 The charity Action against Medical Accidents works with around 4000 people every year who have been affected by ‘patient safety incidents’ (the term used by the NHS). Dr Stuart Gray, whose father died as a result of a massive overdose of diamorphine administered by an out-of-hours GP from Germany, says ‘It is deeply disturbing to be informed that so many NHS bodies still completely disregard the National Patient Safety Agency safety alerts’.3 A public inquiry is currently investigating the deaths of hundreds of patients at Mid Staffordshire NHS Foundation Trust. Adverse events are not always immediately apparent. Radiotherapy to the breast is one example where many women have had progressive problems resulting in, for instance, bone necrosis and soft tissue fibrosis, leading in some cases to bone fractures, arm amputations, and second cancers.4 Indeed, according to Jan Stjernsward, ‘routine use of radiotherapy in early breast cancer … seemed to be associated with increased mortality, an iatrogenic failure’.5 However, complementary medicine, including acupuncture, can sometimes ameliorate such problems. So can we all please work in a truly holistic manner, and allow patients to use the best of complementary therapy together with all that orthodox medicine has to offer? It seems to me that orthodox medicine is in greater need than complementary of the maxim ‘First do no harm’.

Abstract P4-11-09: Evidence of Better Cosmetic Outcome after Intra-Operative Radiotherapy with the TARGIT Technique Compared with External Beam Radiotherapy for Early Breast Cancer: Objective Assessment of Patients Enrolled in a Randomised Controlled Trial

Abstract Background: The international randomised TARGIT Trial started accrual in 2000 to determine if there is non-inferiority between the novel technique of TARGIT [intra-operative radiotherapy with Intrabeam® (Carl Zeiss, Germany)] and conventional external beam radiotherapy (EBRT) in women with early breast cancer, with the main outcome measure of risk of local relapse within the treated breast. We report here the data from a sub-protocol assessing cosmesis in a sub-set of patients over 50 years old participating in the TARGIT Trial from one centre (Perth, Australia). Materials and methods: Frontal digital photographs from 114 patients (59 TARGIT, 55 EBRT) taken at baseline and 1, 2 and 3 years after completion of breast conserving surgery were assessed blinded to allocated treatment using specialist software (BCCT.core 2.0, INESC Porto, Portugal) which produces a composite score (Excellent, Good, Fair, Poor) based on asymmetry, colour and scar. Results: Median age at randomisation was 61 (IQR 56-67) years; all patients were free from recurrence. The categories Excellent and Good; Fair and Poor; were combined to form EG and FP, respectively. Results are shown in Figure 1. On average patients in the TARGIT group attained EG significantly sooner than those in the EBRT group; a higher cumulative proportion of patients in the TARGIT group had attained EG by each of the three annual examinations post surgery, Log Rank test p=0.0244. By 1 year post surgery 74.6% (SE 5.7%) and 56.4% (SE 6.7%) had achieved EG cosmesis in the TARGIT and EBRT groups respectively. Discussion: These results indicate that the cosmetic effects of targeted radiotherapy using Intrabeam® are better than those obtained with conventional EBRT, with the largest difference one year after surgery. Figure 1. Cosmetic outcome by randomised treatment Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-11-09.

Intraoperative Radiotherapy as Accelerated Partial Breast Irradiation for Early Breast Cancer

Intraoperative radiotherapy (IORT) was originally introduced in breast cancer treatment as an "anticipated boost" during the procedure of breast conserving surgery (BCS). In addition to whole breast irradiation (WBI), it has yielded excellent long-term results [31, 38]. Under the assumption that the majority of in-breast tumor recurrences (IBTR) occur in the originally affected site, accelerated partial breast irradiation (APBI) as the sole treatment modality was initiated in several studies and with different techniques, one of which was IORT first with electrons, later also with conventional x-rays [29]. The question whether and for whom the gold standard of WBI may be replaced by APBI - especially IORT - alone has recently been one of the most controversial issues of adjuvant therapy for breast cancer. Two recently published studies by Veronesi et al. [36] and Vaidya et al. [35] presenting shortterm results of single shot IORT with electrons (ELIOT) and with an orthovoltage system (TARGIT), respectively, have further invigorated this discussion as illustrated by several letters to the editor commenting on the TARGIT study. While Vaidya et al. [35] indicate their results of IORT alone as "an alternative to WBI for selected patients" and one editorial even proclaims it as standard [6], all the authors of the respective letters [10, 16, 27, 33] strongly disagree with this conclusion. The present editorial comments on the two publications and, furthermore, provides respective statements of the breast cancer expert panel of the German Society of Radiation Oncology (DEGRO).

Cosmetic outcome one, two and three years after intra-operative radiotherapy compared with external beam radiotherapy for early breast cancer: an objective assessment of patients from a randomised controlled trial

Background: The randomised controlled TARGIT Trial was designed to determine non-inferiority between the novel technique of TARGIT [intra-operative radiotherapy with Intrabeam® (Carl Zeiss, Germany)] and conventional external beam radiotherapy (EBRT) in women with early breast cancer. The main outcome objective is risk of local relapse within the treated breast. We report here data from a sub-protocol assessing cosmesis in 114 women over 50 years participating in the TARGIT Trial from one centre (Perth, Australia).

Clinical observation of early breast cancer after breastconserving surgery and radiotherapy

Objective To observe the oncololigcal and cosmetic outcomes and complication of breastconserving surgery and radiotherapy for early breast cancer. Methods A total of 78 early breast cancer patients, who were treated in the First People's Hospital of Pingdingshan between January 2001 and September 2008, were identified and followed. Among them, 36 were in stage Ⅰ and 42 in stage Ⅱ. Tangential irradiation was used with a dose of 50 Gy. Tumor bed received a boost dose of 10 Gy electron beam. For axillary lymph node-positive patients, ipsilateral supraclavicular field was hybrid irradiated with 50 Gy X and electron beam.Results The total follow-up ranged from 6 to 98 months. Local recurrence was observed among 4.9% of the patients. The 3-year and 5-year overall survival rate were 96.6% and 92.7% ,respectively. The breast cosmetic satisfaction rate was 94.9%. The main complications reported were acute skin reaction and upper limb edema.Conclusion Breast-conserving surgery and post-operative radiotherapy in early breast cancer patients can lead to satisfactory survival rates and cosmetic effects and hence improved life quality. Key words: Breast neoplasms; Breast conserving therapy; Radiotherapy

Quality of life after breast radiotherapy

1 Hopwood P, Haviland JS, Sumo G, Mills J, Bliss JM, Yarnold JR. Comparison of patient-reported breast, arm, and shoulder symptoms and body image after radiotherapy for early breast cancer: 5-year follow-up in the randomised Standardisation of Breast Radiotherapy (START) trials. Lancet Oncol 2010; 11: 231–40. 2 Carling M, Goodare H, Ironside A, Millington J, Rogers C. Radiotherapy hypofractionation in early breast cancer. Lancet 2008; 372: 204–05. 3 Bartelink H, Arriagada R. Hypofractionation in radiotherapy for breast cancer. Lancet 2008; 371: 1050–52. 4 Withers HR. Radiation biology and treatment options in radiation oncology. Cancer Res 1999; 59 (suppl): 1676–84. 5 Powell S, Cooke J, Parsons C. Radiation-induced brachial plexus injury: followup of two diff erent fractionation schedules. Radiother Oncol 1990; 18: 213–20. 6 Hanley B, Staley K. Yesterday’s women: the story of R.A.G.E. London: Macmillan Cancer Support, 2006. Correspondence Quality of life after breast radiotherapy

Thermoluminescence dosimetry for skin dose assessment during intraoperative radiotherapy for early breast cancer

Dosimetry for intraoperative radiotherapy (IORT) after wide local excision for breast cancer using a 50 kV X-ray needle (Intrabeam) was performed in vivo using thermoluminescence dosimetry. Eight LiF:Mg,Ti chips were placed on the skin around the incision site after wide local excision while the tumour bed was irradiated to a prescribed dose of 5 Gy 10 mm from the applicator surface. The maximum and mean measured skin dose for 57 patients ranged from 0.64 to 7.1 Gy and 0.56 to 4.78 Gy, respectively, reflecting different tissue thicknesses overlying the applicator. The average maximum dose of 2.93+/-1.46 Gy was below the threshold for severe radiation skin toxicity.

Randomised phase II trial of hyperbaric oxygen therapy in patients with chronic arm lymphoedema after radiotherapy for cancer

Background A non-randomised phase II study suggested a therapeutic effect of hyperbaric oxygen (HBO) therapy on arm lymphoedema following adjuvant radiotherapy for early breast cancer, justifying further investigation in a randomised trial. Methods Fifty-eight patients with ⩾15% increase in arm volume after supraclavicular ± axillary radiotherapy (axillary surgery in 52/58 patients) were randomised in a 2:1 ratio to HBO ( n = 38) or to best standard care ( n = 20). The HBO group breathed 100% oxygen at 2.4 atmospheres absolute for 100 min on 30 occasions over 6 weeks. Primary endpoint was ipsilateral limb volume expressed as a percentage of contralateral limb volume. Secondary endpoints included fractional removal rate of radioisotopic tracer from the arm, extracellular water content, patient self-assessments and UK SF-36 Health Survey Questionnaire. Findings Of 53/58 (91.4%) patients with baseline assessments, 46 had 12-month assessments (86.8%). Median volume of ipsilateral limb (relative to contralateral) at baseline was 133.5% (IQR 126.0–152.3%) in the control group, and 135.5% (IQR 126.5–146.0%) in the treatment group. Twelve months after baseline the median (IQR) volume of the ipsilateral limb was 131.2% (IQR 122.7–151.5%) in the control group and 133.5% (IQR 122.3–144.9%) in the treatment group. Results for the secondary endpoints were similar between randomised groups. Interpretation No evidence has been found of a beneficial effect of HBO in the treatment of arm lymphoedema following primary surgery and adjuvant radiotherapy for early breast cancer.

Cosmetic outcome two and three years after intraoperative radiotherapy compared with external beam radiotherapy for early breast cancer: An objective assessment of patients from a randomized controlled trial.

570 Background: The international randomized TARGIT Trial, due to finish accrual in 2010, was designed to determine if there is equivalence between the novel technique of IORT (intraoperative radiotherapy with Intrabeam [Carl Zeiss, Germany]) and conventional external beam radiotherapy (EBRT) in women with early breast cancer. The main outcome objective is risk of local relapse within the treated breast. We report here the two- and three-year data from a subprotocol assessing cosmesis in a subset of 105 women over 50 participating in the TARGIT Trial from one center (Perth, Australia). Methods: Frontal digital photographs from patients at one TARGIT center (Perth, Australia) were assessed, blind to treatment, using specialist software (BCCT.core 2.0, INESC Porto, Portugal) that produces a composite score (excellent, good, fair, poor) based on symmetry, color, and scar. Statistical advice was given by the Biostatistics Group, The Joint UCL, UCLH, & Royal Free Biomedical Research Unit. Results: 105 patients have been assessed, median age at randomization 62 years (range 50 to 82). Photographs were taken 2 years (median 23 months, n=105) and 3 years (median 35 months, n=84) after initial breast conserving surgery; none had subsequent breast surgery. The scores were dichotomized into excellent and good, and fair and poor (Table). After 2 years 78% (43/55) of the IORT patients and 74% (37/50) of EBRT patients had excellent or good cosmetic outcome. 84 of these patients were assessed again at 3 years with similar results. Conclusions: These results indicate that there is no evidence of a difference in comesis between IORT and conventional EBRT, two and three years after surgery. Cosmetic outcome by randomized treatment Year 2 assessment (n=105) Year 3 assessment (n=84*) Excellent/good Fair/poor Excellent/good Fair/poor IORT 43 12 36 6 EBRT 37 13 32 10 * Statistical note: These patients are a subset of the 105 patients assessed at year 2 and the two chi-squared tests (below) are not independent: Year 2: Chi- Square = 0.25, df=1, p = 0.62 Year 3: Chi-Square = 1.24, df=1, p = 0.27. No significant financial relationships to disclose.

Fewer fractions of adjuvant external beam radiotherapy for early breast cancer are safe and effective and can now be the standard of care: Why the UK’s NICE accepts fewer fractions as the standard of care for adjuvant radiotherapy in early breast cancer

Fractionation regimes for individual tumour sites have varied greatly across the UK for many years. This has been particularly true for breast cancer which accounts for up to 40% of a radiotherapy department’s work load. Over the last 30 years or so many UK oncology centres have coped with this large case load and a lack of megavoltage machines by reducing fractionation and routinely using internationally non standard regimes so that these regimes have themselves become one of the options for standard treatment. Nowadays, medicine is largely evidence based rather than historically relying more on clinical experience or intuition. Large studies particularly in the UK and Canada set out to address this question and have shown that fewer fractions are equivalent in terms of local recurrence, late tissue effects and cosmesis. Current studies are focusing on further hypofractionation and partial breast radiotherapy (see papers Yarnold (2010) Is it safe to push “hypofractionation” further?. The Breast (this issue). Lehman (2010) The less than whole breast radiotherapy approach. The Breast (this issue)).

Dosimetric analysis of radiation dose to latissimus dorsi myocutaneous flap in women undergoing adjuvant radiotherapy for early breast cancer—short report

Breast reconstruction following mastectomy often involves the use of regional myocutaneous flaps such as the latissimus dorsi (LDM) and transverse rectus abdominus flaps. A history of previous radiation to the skin paddle of the myocutaneous flap planned for breast reconstruction may cause the plastic surgeon to consider using an alternative muscle flap which has not received radiation. To aid decision-making in the setting of previous radiation, we prospectively assessed the dose given to the latissimus myocutaneous flap of a small series of seven women who were to undergo adjuvant 3-D conformal radiation therapy after breast conservation surgery (four) or mastectomy (three). The skin paddles of this flap were marked using wires prior to the planning CT scan required for 3-D conformal therapy. Radiation dose to the skin paddles was minimal but the LD muscle dose averaged 888 cGy. The thoracodorsal artery received the highest doses of radiation averaging 2,750 cGy with 55.5% of the artery receiving at least 2,500 cGy and 25.3% of the artery receiving at least 4,500 cGy which was almost a prescription radiation dose to the whole breast. The clinical implications of this level of radiation dose to the arterial pedicle are likely minimal because it is a peripheral small blood vessel. The surgeon and the radiation oncologist should be aware of this as a potential factor and its possible effects on breast reconstruction outcome particularly in the midst of other predictors of poor vascularity such as smoking, diabetes, or peripheral vascular disease. We plan to study further the dose to LDM flap in a larger series of women. However, information about dose to planned myocutaneous flap in the setting of history of previous breast radiation can be easily obtained from the radiation plan and should be ascertained prior to breast reconstruction.

Commentary on “Dosimetric analysis of radiation dose to latissimus dorsi myocutaneous flap in women undergoing adjuvant radiotherapy for early breast cancer—short report” by Albuquerque et al.

This paper is a report on a small number of cases; however, the value of the manuscript is the emphasis on the latissimus dorsi myocutaneous flap. This flap has tended to be pushed aside by free tissue transfer or TRAM flaps, etc. This is unfortunate because the latissimus dorsi flap is easy to perform, very reliable, and usually of the correct size. It is reliable even after radiation. I was pleased to note that a large series is anticipated. I look forward to future studies by this group.

Interval between breast-conserving surgery and radiotherapy in early-breast cancer: How long before an effect on local control?

Interval between breast-conserving surgery and radiotherapy in early-breast cancer: How long before an effect on local control?

364 The serious uncommon side effects after radiotherapy in early breast cancer

364 The serious uncommon side effects after radiotherapy in early breast cancer

Partial Breast Irradiation or Whole Breast Radiotherapy for Early Breast Cancer: A Meta-Analysis of Randomized Controlled Trials

The purpose of the study was to compare treatment outcomes in patients with breast cancer treated with partial breast irradiation (PBI) and of those treated with whole breast-radiation therapy (WBRT). We conducted a systematic review and meta-analysis of published randomized clinical trials comparing PBI versus WBRT. Primary outcome was overall survival and secondary outcomes were locally, axillary, supraclavicular, and distant recurrences. A search of the literature identified three trials with pooled total of 1,140 patients. We found no statistically significant difference between partial and whole breast radiation arms associated with death (OR 0.912, 95% CI 0.674-1.234, p = 0.550), distant metastasis (OR 0.740, 95% CI, 0.506-1.082, p = 0.120), or supraclavicular recurrences (pooled OR 1.415, 95% CI 0.278-7.202, p = 0.560). However, PBI was statistically significantly associated with an increased risk of both local (pooled OR 2.150, 95% CI, 1.396-3.312; p = 0.001) and axillary recurrences (pooled OR 3.430, 95% CI, 2.058-5.715; p < 0.0001) compared with whole breast-radiation. Partial breast irradiation does not seem to jeopardize survival and may be used as an alternative to whole breast-radiation. Nevertheless the issue of loco-regional recurrence needs to be further addressed.