Skin reducing mastectomy and immediate reconstruction: The effect of radiotherapy on complications and patient reported outcomes

Aim

Skin reducing mastectomy, dermal sling and immediate implant reconstruction (SRMIR) is an emerging technique where, de-epithelialised inferior skin flap sutured to pectoralis major provides vascularised, dermal sling for the implant. We aimed to assess patient satisfaction following SRMIR and determine if radiotherapy affected patient reported outcomes.

Method

A prospective database of women undergoing SRMIR was analysed. SRMIR was performed in 92 women (116 breasts). Radiotherapy was received by 45 women and it was not required in 47 women. Forty eight women had contralateral surgery: 21 breast reduction/mastopexy, 1 augmentation, 26 mastectomy/reconstruction. A validated breast evaluation questionnaire provided patient reported outcomes.

Results

Median follow up was 20 months. Early complications were similar in both groups, but those in the radiotherapy group had a higher incidence of implant loss (6/45 = 13% vs 1/47 = 2%; p = 0.06) and grade III/IV capsular contracture (11/45 = 24% vs 6/47 = 13%; p = 0.20).The outcome questionnaire was sent to 83 women who were disease free and had retained their implants. Sixty three women responded (76%). Patient reported satisfaction was high, with or without radiotherapy. Women receiving radiotherapy gave lower scores, but it was statistically significant only for general appearance and symmetry.

Conclusions

Although complications after radiotherapy are higher in patients who had SRMIR, the majority of women who retained their implant are highly satisfied with their reconstruction. Majority of these patients were happy to recommend SRMIR procedure to their friend.     

Ductal carcinoma in situ of the breast in younger women: A subgroup of patients at high risk

Background

After breast conservative treatment (BCT), young age is a predictive factor for recurrence in patients with Ductal Carcinoma In Situ (DCIS) of the breast. The purpose of this study was to evaluate predictive factors for recurrence and outcomes in these younger women (under 40 years) treated for pure DCIS.

Methods

From 1974 to 2003, 207 cases were collected in 12 French Cancer Centers. Median age was 36.3 years and median follow-up 160 months. Seventy four (35.8%) underwent mastectomy, 67 (32.4%) lumpectomy alone and 66 (31.9%) lumpectomy plus radiotherapy.

Results

37 recurrences occurred (17.8%): 14 (38%) were in situ and 23 (62%) invasive. After BCT, the overall rate of recurrence was 27% (33% in the lumpectomy plus radiotherapy group vs. 21% in the lumpectomy alone group). Comedocarcinoma subtype (p = 0.004), histological size more than 10 mm (p = 0.011), necrosis (p = 0.022) and positive margin status (p = 0.019) were statistically significant predictive factors for recurrence. The actuarial 15-year rates of local recurrence were 29%, 42% and 37% in the lumpectomy alone, lumpectomy and whole breast radiotherapy and lumpectomy + whole breast radiotherapy with additional boost groups respectively. After recurrence, the 10-year overall survival rate was 67.2%.

Conclusion

High recurrence rates (mainly invasive) after BCT in young women with DCIS are confirmed. BCT in this subgroup of patients is possible if clear and large margins are obtained, tumor size is under 11 mm and necrosis- and/or comedocarcinoma-free.     

Intra-operative radiotherapy of rectal cancer: Results of the French multi-institutional randomized study

Purpose

To assess efficacy and tolerance of intra-operative radiation therapy (IORT) in patients suffering from locally advanced rectal cancer, treated with preoperative radiotherapy followed by surgical resection.

Methods and materials

In this French, multicenter, comparative, phase III study, 142 patients with locally advanced rectal cancer (T3 or T4 or N+, and M0), treated with a 4-week preoperative radiotherapy (40 grays) were randomly assigned to either surgical resection alone (Control group: n = 69) or combined to 18-gray intra-operative radiation therapy (IORT group: n = 73) between 1993 and 2001.

Results

The 5-year cumulative incidence of local control was 91.8% with IORT and 92.8% with surgery alone (p = 0.6018); the mean duration without local relapse (Kaplan-Meier method) was 107 versus 126 months, respectively. No statistically significant difference was demonstrated for overall survival (p = 0.2578) disease-free survival (p = 0.7808) and probability of metastatic relapse (p = 0.6037) with 5-year cumulative incidences of 69.8% versus 74.8%, 63.7% versus 63.1%, and 26.1% versus 30.2%, respectively. 48 patients of the IORT group and 53 patients of the control group were alive with a median follow-up of 60.1 and 61.2 months, respectively. Post-operative complications were observed in the IORT group in 21 patients (29.6%) and in the control group in 13 patients (19.1%) (p = 0.15), with an acceptable tolerance profile.

Conclusions

Although this randomized study did not demonstrate any significant improvement in local control and disease-free survival in rectal cancer patients treated with preoperative radiation therapy receiving IORT or not, it confirmed the technical feasibility and the necessity for evaluating IORT for rectal carcinoma in further clinical studies.     

Y-box-binding protein 1 (YB1) in breast carcinomas: Relation to aggressive tumor phenotype and identification of patients at high risk for relapse

Aims

To investigate the expression pattern of Y-box-binding protein 1 (YB1) in breast carcinomas, its clinicopathological and prognostic value, and its association with the breast cancer stem cell phenotype [CD44⁺/CD24^−/low].

Methods and results

Immunohistochemistry was performed on 225 paraffin embedded specimens of invasive breast carcinomas to detect the expression of the proteins YB1, ER, PR, HER2, p53, Ki67, bcl-2, CD44 and CD24. YB1 protein was detected in the nuclei, the cytoplasm and the stroma of the tumor cells. Cytoplasmic YB1 was detected more often in carcinomas of ductal type (p = 0.002), of higher nuclear grade (p < 0.001), with lack of ER expression (p = 0.002), positive expression of p53 and Ki67 (p = 0.002 and p = 022, respectively), and with present CD44⁺/CD24^−/low breast cancer stem cells (p = 0.001), while its association with bcl-2 was found to be inverse (p = 0.042). Nuclear YB1 was found to exert unfavorable impact on the disease-free survival of the unselected patients (p = 0.05) and the patients having been subjected to adjuvant chemotherapy and radiotherapy (p = 0.036 and p = 0.05, respectively).

Conclusions

Cytoplasmic YB1 is associated with an aggressive and “stem cell-like” tumor phenotype, while nuclear localization discriminates patients at high risk for recurrence, especially those who are subjected to chemo- and radiotherapy.     

Treatment outcomes and unfavorable prognostic factors in patients with occult breast cancer

Aims

The purpose of this study was to evaluate the treatment outcomes and prognostic factors in patients with occult breast cancer (OBC).

Methods

We retrospectively analyzed 95 patients with OBC who were treated at our facility between January 1998 and June 2010. Of the 95 patients, 64 underwent mastectomy plus axillary lymph node dissection (ALND) with or without post-mastectomy radiation (Mast + ALND group), 13 underwent ALND followed by ipsilateral breast radiotherapy (BR + ALND group) and the remaining 18 were treated with ALND (ALND group).

Results

Patients who underwent Mast + ALND or BR + ALND had significantly improved rates of locoregional recurrence-free survival (LRFS) and recurrence/metastasis-free survival (RFS) than patients who only underwent ALND (p < 0.05). There were no significant differences in the LRFS (p = 0.718), RFS (p = 0.935) and breast cancer-specific survival (BCSS) (p = 0.991) rates between the patients who underwent Mast + ALND compared with those who received BR + ALND. Multivariate analysis revealed that patients with four or more involved lymph nodes had significantly worse outcomes (p = 0.042, HR = 4.63, 95% CI = 1.66–32.47 for BCSS and p = 0.038, HR = 3.62, 95% CI = 1.08–20.77 for RFS).

Conclusions

Patients with OBC who received ALND and subsequent breast radiotherapy had similar outcomes to patients who underwent mastectomy. The presence of four or more involved lymph nodes may independently predict poor outcomes of OBC.     

Effect of neoadjuvant chemotherapy on outcomes of immediate free autologous breast reconstruction

Background

Neoadjuvant chemotherapy (NC) is increasingly being utilised although the effects on outcomes of free autologous breast reconstruction and adjuvant treatment remain unclear. The aim of this study was to examine the effect of NC on complications following immediate free flap breast reconstruction.

Methods

A prospective study of immediate free flap breast reconstructions comparing patients who received NC with those who did not was conducted in a single specialist regional unit.

Results

Eighty-seven patients (95 flaps) were included in the study, 30 of which (35 flaps) received NC followed by free flap breast reconstruction. Twenty patients in the NC group had one or more complications compared with 37 patients in the control group (p = 0.87). Nine patients in the NC group had more than one complication compared with 11 patients in the control group, although this difference was not significant (p = 0.26). Both obesity (p = 0.016) and current cigarette smoking (p = 0.014) were significantly associated with the occurrence of any complication in patients who had received NC. Adjuvant radiotherapy was delayed in 3 patients in the NC group, and adjuvant chemotherapy was delayed in 3 control patients (p = 1). The mean preoperative haemoglobin was significantly lower in the NC group than in the control group (p = 0.00037), although there was no significant difference in blood transfusion requirements.

Conclusions

Patients undergoing immediate autologous breast reconstruction following NC have a similar complication and reoperation rate to patients not receiving NC. Preoperative blood haemoglobin level was found to be significantly lower following NC and postoperative blood transfusion triggers should take this into account.     

Benefits and drawbacks of short-course preoperative radiotherapy in rectal cancer patients aged 75 years and older

Purpose

To study incidence of local recurrences, postoperative complications and survival, in patients with rectal carcinoma aged 75 years and older, treated with either surgery and pre-operative 5 × 5 Gy radiotherapy or surgery alone.

Patients and methods

A random sample of patients aged over 75 years with pT2-T3, N0-2, M0 rectal carcinoma diagnosed between 2002 and 2004 in the Netherlands was included, treated with surgery alone (N = 296) or surgery in combination with pre-operative radiotherapy (N = 346). Information on local recurrent disease, postoperative complications, ECOG-performance score and comorbidity was gathered from the medical files.

Results

Local recurrences developed less frequently in patients treated with pre-operative radiotherapy compared to surgery alone (2% vs 6%, p = 0.002). Postoperative complications developed more frequently in irradiated patients (58% vs 42%, p < 0.0001). Especially deep infections (anastomotic leakage, pelvic abscess) were significantly increased in this group (16% vs 10%, p = 0.02). 30-day mortality was equal in both groups (8%). A significant increase in postoperative complication rate and 30-day mortality was only seen in those with “severe comorbidity” compared to patients without comorbidity (respectively 58% and 10% vs 43% and 3%), COPD (59% and 12%), diabetes (60% and 11%) and cerebrovascular disease (62% and 14%). In multivariable analysis, postoperative complications predicted 5-year survival.

Conclusion

Elderly patients receiving pre-operative radiotherapy show a lower local recurrence rate. However, as incidence rates of local recurrent disease are low and incidence of postoperative complications is increased in irradiated patients, omitting preoperative RT may be suitable in elderly patients with additional risks for complications or early death.     

Adjuvant chemoradiotherapy with or without intraoperative radiotherapy for the treatment of resectable locally advanced gastric adenocarcinoma

Purpose

To document the long-term efficacy of intraoperative electron radiotherapy (IOERT) followed by concurrent chemotherapy and external-beam radiotherapy (EBRT) in the management of locally advanced gastric cancer.

Materials and methods

A total of 97 consecutive patients with T3/4 or N+ gastric adenocarcinoma were enrolled. Fifty-one patients received adjuvant chemoradiotherapy (EBRT group) and 46 received IOERT (dose range, 12-15 Gy) followed by chemoradiotherapy (EBRT + IOERT group).

Results

The 5-year locoregional control rates were 50% and 35% in the two groups with or without IOERT, respectively (p = 0.04). Two patients had recurrence within the IOERT field in the EBRT + IOERT group and 14 patients recurred in the same area in the EBRT group (p = 0.02). Multivariate analyses revealed that adjuvant IOERT was an independent prognosticator for both local-regional control (p = 0.02) and disease-free survival (p = 0.05). G3/4 late toxicity was observed in 5 patients in the EBRT + IOERT group, but none in the EBRT group (p = 0.02).

Conclusions

Higher radiation dose may contribute to the improvement of local control, especially in the field encompassed by IOERT. The addition of IOERT to surgery and adjuvant chemoradiation deserves further investigation in a randomized trial.     

“Axillary recurrences after sentinel lymph node biopsy: A multicentre analysis and follow-up of sentinel lymph node negative breast cancer patients”

Introduction

The objective of this study was to conduct a multicentre data analysis to identify prognostic factors for developing an axillary recurrence (AR) after negative sentinel lymph node biopsy (SLNB) in a large cohort of breast cancer patients with long follow-up.

Patients and methods

The prospective databases from different hospitals of clinically node negative breast cancer patients operated on between, 2000 and 2002 were analyzed. SLNB was performed and pathological analysis done by local pathologists according to national guidelines. Adjuvant treatment was given according to contemporary guidelines. Multivariate analysis was performed using all available variables, a p-value of <0,05 was considered to be significant.

Results

A total of 929 patients who did not undergo axillary lymph node dissection were identified. After a median follow up of 77 (range 1–106) months, fifteen patients developed an isolated AR (AR rate 1,6%). Multivariate analysis showed that young age (p = 0.007) and the absence of radiotherapy (p = 0.010) significantly increased the risk of developing an AR. Distant metastasis free survival (DMFS) was significantly worse for patients with an AR compared to all other breast cancer patients (p < 0,0001).

Conclusion

Even after long-term follow up, the risk of developing an AR after a negative SLN in breast cancer is low. Young age and absence of radiation therapy are highly significant factors for developing an axillary recurrence. DMFS is worse for AR patients compared to patients initially diagnosed with N0 or N1 disease.     

Association of breast tumour bed seroma with post-operative complications and late normal tissue toxicity: Results from the Cambridge Breast IMRT trial

Aims

There are two main surgical techniques for managing the tumour bed after breast cancer excision. Firstly, closing the defect by suturing the cavity walls together and secondly leaving the tumour bed open thus allowing seroma fluid to collect. There is debate regarding which technique is preferable, as it has been reported that a post-operative seroma increase post-operative infection rates and late normal tissue side effects.

Methods

Data from 648 patients who participated in the Cambridge Breast IMRT trial were used. Seromas were identified on axial CT images at the time of radiotherapy planning and graded as not visible/subtle or easily visible. An association was sought between the presence of seroma and the development of post-operative infection, post-operative haematoma and 2 and 5 years normal tissue toxicity (assessed using serial photographs, clinical assessment and self assessment questionnaire).

Results

The presence of easily visible seroma was associated with increased risk of post-operative infection (OR = 1.80; p = 0.004) and post-operative haematoma (OR = 2.1; p = 0.02). Breast seroma was an independent risk factor for whole breast induration and tumour bed induration at 2 and 5 years. The presence of breast seroma was also associated with inferior overall cosmesis at 5 years. There was no significant association between the presence of seroma and the development of either breast shrinkage or breast pain.

Conclusion

The presence of seroma at the time of radiotherapy planning is associated with increased rates of post-operative infection and haematoma. It is also an independent risk factor for late normal tissue toxicity. This study suggests that full thickness surgical closure may be desirable for patients undergoing breast conservation and radiotherapy.     

Atherosclerotic lesions in lymphoma survivors treated with radiotherapy

Background and purpose

Radiotherapy causes premature atherosclerosis in Hodgkin’s lymphoma survivors (HLSs). We determined whether atherosclerosis within the radiation field was predicted by traditional risk factors independent of radiation and compared the extent of atherosclerosis in HLSs treated with mantle field radiotherapy with non-irradiated patients.

Material and methods

Forty-three HLSs (median age 50 years, range 38–63) treated with mantle field radiotherapy were included. Cardiovascular risk factors were registered at first follow-up (FU-1) 5–13 years after treatment. A second follow-up (FU-2) occurred 18–27 years after treatment. At FU-2, in-field atherosclerosis was assessed by computed tomography with calculation of coronary artery calcium volume score (CACS) and pre-cranial artery atherosclerosis score (PAS). Peripheral endothelial dysfunction was assessed by ante-brachial strain-gauge plethysmography. CT angiography of pre-cranial vessels was also performed in 43 non-irradiated patients.

Results

Multiple linear regression analyses showed that cholesterol at FU-1 was a predictor of CACS (β 308 (95% CI 213–403), p < 0.001), PAS (β 3.67 (95% CI 2.29–5.04), p < 0.001) and peripheral endothelial dysfunction (β 2.74 (95% CI 0.47–5.01), p = 0.02). There were more atherosclerotic lesions in HLSs (n = 141) than in non-irradiated patients (n = 73, p = 0.001).

Conclusion

Irradiated arteries are characterized by widespread atherosclerotic lesions aggravated by elevated levels of cholesterol.     

Benefits of postoperative radiotherapy in multimodality treatment of resected small-cell lung cancer with lymph node metastasis

Aim

The purpose of this study is to evaluate the role of postoperative radiotherapy (PORT) in resected small-cell lung cancer (SCLC).Methods: This study retrospectively analyzed 143 patients with completely resected SCLC in our institution between 1996 and 2011. The primary endpoint was overall survival (OS). The log-rank test and Cox regression model were used to evaluate the factors influencing local-regional recurrence (LRR) and OS.

Results

The median OS for the entire population was 34 months, and the 5-year OS rate was 34.6%. In multivariate analysis, age, surgical procedure, pathology stage, adjuvant chemotherapy and distant relapse were significant factors for survival. For the whole population, PORT had no effect on OS, with a median OS of 40 months in the PORT group versus 27 months in the non-PORT group (p = 0.260). However, in patients with N1 disease, the median OS were 40 months in the PORT group versus 14 months in the non-PORT group (p = 0.032). The corresponding OS in N2 patients were 35 months versus 17 months, respectively (p = 0.040). Similarly, PORT significantly reduced the LRR in patients with positive lymph node. For patients with N1 disease, the 3-year LRR rate was 0.0% in the PORT group versus 14.3% in the non-PORT group (p = 0.037). The corresponding LLR rate in N2 patients was 4.2% versus 56.6% (p < 0.001).

Conclusion

PORT significantly reduced LRR and improved OS in patients with regional metastasis SCLC. We suggest supplementing PORT in the multimodality treatment of resected SCLC with lymph node metastasis.     

Optimising measles virus-guided radiovirotherapy with external beam radiotherapy and specific checkpoint kinase 1 inhibition

Background and purpose

We previously reported a therapeutic strategy comprising replication-defective NIS-expressing adenovirus combined with radioiodide, external beam radiotherapy (EBRT) and DNA repair inhibition. We have now evaluated NIS-expressing oncolytic measles virus (MV-NIS) combined with NIS-guided radioiodide, EBRT and specific checkpoint kinase 1 (Chk1) inhibition in head and neck and colorectal models.

Materials and methods

Anti-proliferative/cytotoxic effects of individual agents and their combinations were measured by MTS, clonogenic and Western analysis. Viral gene expression was measured by radioisotope uptake and replication by one-step growth curves. Potential synergistic interactions were tested in vitro by Bliss independence analysis and in in vivo therapeutic studies.

Results

EBRT and MV-NIS were synergistic in vitro. Furthermore, EBRT increased NIS expression in infected cells. SAR-020106 was synergistic with EBRT, but also with MV-NIS in HN5 cells. MV-NIS mediated ¹³¹I-induced cytotoxicity in HN5 and HCT116 cells and, in the latter, this was enhanced by SAR-020106. In vivo studies confirmed that MV-NIS, EBRT and Chk1 inhibition were effective in HCT116 xenografts. The quadruplet regimen of MV-NIS, virally-directed ¹³¹I, EBRT and SAR-020106 had significant anti-tumour activity in HCT116 xenografts.

Conclusion

This study strongly supports translational and clinical research on MV-NIS combined with radiation therapy and radiosensitising agents.     

Breast conserving surgery in combination with intraoperative radiotherapy after previous external beam therapy: an option to avoid mastectomy

Purpose

Mastectomy is the standard procedure in patients with in-breast tumor recurrence (IBTR) or breast cancer after irradiation of the chest due to Hodgkin’s disease. In certain cases a second breast conserving surgery (BCS) in combination with intraoperative radiotherapy (IORT) is possible. To date, data concerning BCS in combination with IORT in pre-irradiated patients are limited. This is the first pooled analysis of this special indication with a mature follow-up of 5 years.

Methods

Patients with IBTR after external beam radiotherapy (EBRT; treated in two centers) for breast cancer were included. Patients with previous EBRT including the breast tissue due to other diseases were also included. IORT was performed with the Intrabeam?-device using low kV X-rays. Clinical data including outcome for all patients and toxicity for a representative cohort (LENT-SOMA scales) were obtained. Statistical analyses were done including Kaplan–Meier estimates for local recurrence, distant metastasis and overall survival.

Results

A total of 41 patients were identified (39 patients with IBTR, 2 with Hodgkin`s disease in previous medical history). Median follow-up was 58 months (range 4–170). No grade 3/4 acute toxicity occurred within 9 weeks. Local recurrence-free survival rate was 89.9% and overall survival was 82.7% at 5 years. Seven patients developed metastasis within the whole follow-up.

Conclusions

BCS in combination with IORT in IBTR in pre-irradiated patients is a feasible method to avoid mastectomy with a low risk of side effects and an excellent local control and good overall survival.

     

Breast conserving surgery after neoadjuvant therapy for large primary breast cancer

Aim

The aim of this study was to evaluate the safety of breast conserving surgery in patients with breast tumours satisfactorily downstaged after neoadjuvant therapy.

Methods

A retrospective cohort study was undertaken to analyze the loco-regional recurrence (LRR) after breast conserving surgery. We enrolled 88 patients with breast cancer subjected to neoadjuvant therapy (NAT group) who achieved an objective response due to neoadjuvant treatment and compared them with 191 patients with early breast cancer (EBC group) who were submitted to primary conserving surgery. Lumpectomy or quadrantectomy with axillary lymph node dissection was performed in all patients who received adjuvant radiotherapy. Systemic adjuvant therapy was offered to all patients. The mean periods of observation were 61.3 months in the NAT group and 67.5 months in the EBC group.

Results

The mean age was 53 years in the NAT group and 56 years in the EBC group (p = 0.04). There was no histological type and histological grade difference between groups. In the NAT group, the mean diameter of residual tumour was lower and the mean volume of breast tissue resection was higher than in the EBC group (p = 0.01 and p = 0.002, respectively). The ipsilateral recurrence rate was 7.9% in the NAT group and 7.8% in the EBC group (p = 0.9). The most important predictive factor of recurrence in the NAT group was the age of patient.

Conclusion

Breast conserving therapy is a safe procedure in satisfactorily downstaged breast cancer after neoadjuvant therapy.     

Prognosis following local recurrence after breast conserving treatment in young women with early breast cancer

Background

Few studies have focussed on the prognosis of young women with local recurrence (LR) after breast-conserving therapy and the factors that can be used to predict their prognosis.

Methods

We studied the outcome and related prognostic factors in 124 patients with an isolated local recurrence in the breast following breast-conserving surgery and radiotherapy for early stage breast cancer diagnosed at the age of 40 years or younger.

Results

The median follow-up of the patients after diagnosis of LR was 7.0 years. At 10 years from the date of salvage treatment, the overall survival rate was 73% (95% CI, 63–83), the distant recurrence-free survival rate was 61% (95% CI, 53–73), and the local control rate (i.e. survival without subsequent LR or local progression) was 95% (95% CI, 91–99). In the multivariate analysis, the risk of distant metastases also tended to be higher for patients with LR occurring within 5 years after BCT, as compared to patients with LR more than 5 years after BCT (Hazard ratio [HR], 1.89; p = 0.09). A worse distant recurrence-free survival was also observed for patients with a LR measuring more than 2 cm in diameter, compared to those with a LR of 2 cm or smaller (HR, 2.88; p = 0.007), and for patients with a LR causing symptoms or suspicious findings at clinical breast examination, compared to those with a LR detected by breast imaging only (HR 3.70; p = 0.03).

Conclusions

These results suggest that early detection of LR after BCT in young women can improve treatment outcome.     

Acute toxicity of intraoperative radiotherapy and external beam-accelerated partial breast irradiation in elderly breast cancer patients

Background and purpose

We investigated the acute toxicity of accelerated partial breast irradiation using external beam (EB-APBI) or intraoperative radiotherapy (IORT) techniques in elderly breast cancer patients.

Materials and methods

Women ≥ 60 years with unifocal breast tumors of ≤ 30 mm were eligible for this prospective multi-center cohort study. IORT was applied with electrons following lumpectomy (23.3 Gy). EB-APBI was delivered using 3D-CRT or IMRT in 10 daily fractions of 3.85 Gy within 6 weeks after surgery. Acute toxicity was scored using the CTCAE v3.0 at 3 months after treatment. Patient-reported symptoms were analyzed using visual analogue scales (VAS) for pain and fatigue (scale 0–10), and single items from the EORTC QLQ-C30 and Breast Cancer questionnaires.

Results

In total, 267 (IORT) and 206 (EB-APBI) patients were available for toxicity analysis. More patients experienced ≥ grade 2 CTCAE acute toxicity in the IORT group (10.4% IORT and 4.9% EB-APBI; p = 0.03); grade 3 toxicity was low (3.3% IORT and 1.5% EB-APBI; ns); and no grade 4 toxicity occurred. EB-APBI patients experienced less fatigue direct postoperatively (EORTC p < 0.00, VAS p < 0.00). After 3 months only pain, according to the VAS scale, was significantly worse in the EB-APBI group (p < 0.00).

Conclusion

Acute toxicity after IORT and EB-APBI treatment is acceptable.

     

Tumour bed clip localisation for targeted breast radiotherapy: Compliance is proportional to trial-related research activity: Tumour bed clip localisation in breast radiotherapy

Background

In breast cancer, with the increasing use of intensity-modulated radiotherapy (IMRT), the need for accurate tumour bed localisation is paramount. We determined current practice of clip usage in patients referred to a regional centre for radiotherapy following breast conserving surgery. We also investigated whether participation of surgical units in IMRT trials, where tumour bed clip use is emphasised, was associated with clip insertion.

Methods

A retrospective cohort study of consecutive CT planning images (n = 205), of breast cancer patients treated with radiotherapy following breast conserving surgery. Presence and number of clips; referring hospital and referring surgeon of the patient was recorded. This was correlated to previous participation of referring hospital to IMRT trials.

Results

Of 196 eligible patients, 126 (64%) had clips sited, of which 15 (12%) had two or fewer clips. Five referring hospitals were high recruiters (≥14 patients), and five hospitals were low/non-recruiters (≤1 patient) to IMRT trials. Of patients from low/non-recruiting centres, 29 of 43 (67%) had clips omitted, compared to 41 of 153 (27%) from high-recruiting centres (p < 0.001). Median number of clips used in centres recruiting high numbers of patients was four, compared to zero in low recruiting centres. Ten of 31 referring surgeons routinely omitted clips.

Conclusion

Despite inclusion in national guidelines, clip insertion has not become routine in the UK in patients undergoing breast conserving surgery. However, hospitals involved in breast radiotherapy randomised controlled trials are more compliant with clip usage recommendations. Auditing of clip insertion should be considered as a quality control marker in breast surgery.     

Earlier and sustained response with incidental use of cardiovascular drugs among patients with low- to medium-grade meningiomas treated with radiosurgery (SRS) or stereotactic radiotherapy (SRT)

Background and purpose

Beneficial outcome for cancer treated with radiotherapy (RT) and β-blockers has been reported. We hypothesize a potential combined impact of stereotactic RT with incidental use of cardiovascular drugs also in meningiomas.

Materials and methods

In 64 patients with 70 intracranial meningiomas (male/female = 17/53; median follow-up = 2 years) from a prospective database with sustained RT/cardiovascular drug therapy tumor response (progression, stable disease, regression) was evaluated at predefined follow-up intervals of 3, 12 and 24 months based on MR-imaging. For this retrospective cohort analysis stepwise univariate and multivariate analyses for group comparison were performed. Between groups analysis and stepwise uni- and multivariate analysis was performed.

Results

At one year follow-up there was a significant better tumor response for patients with antihypertensives use (p = 0.008) and radiosurgery (SRS) (p = 0.054), the difference between patients with and without antihypertensive medication remains significant in multivariate analysis. Two years after RT, only patients with β-blocker use had a significant better response to RT (p = 0.032). Additionally, for the use of β-blockers a trend toward significance for early tumor response at 3 months compared to the control group was observed (p(one tailed) = 0.059).

Conclusions

Our data suggest that concomitant antihypertensive medication (especially β-blockers) may lead to an earlier and sustained response in stereotactic irradiated low- to medium-grade intracranial meningiomas by affecting the β-adrenergic pathways.     

Risk of second primary lung cancer in women after radiotherapy for breast cancer

Background

Several epidemiological studies have reported increased risks of second lung cancers after breast cancer irradiation. In this study we assessed the effects of the delivered radiation dose to the lung and the risk of second primary lung cancer.

Methods

We conducted a nested case–control study of second lung cancer in a population based cohort of 23,627 early breast cancer patients treated with post-operative radiotherapy from 1982 to 2007. The cohort included 151 cases diagnosed with second primary lung cancer and 443 controls. Individual dose-reconstructions were performed and the delivered dose to the center of the second lung tumor and the comparable location for the controls were estimated, based on the patient specific radiotherapy charts.

Results

The median age at breast cancer diagnosis was 54 years (range 34–74). The median time from breast cancer treatment to second lung cancer diagnosis was 12 years (range 1–26 years). 91% of the cases were categorized as ever smokers vs. 40% among the controls. For patients diagnosed with a second primary lung cancer five or more years after breast cancer treatment the rate of lung cancer increased linearly with 8.5% per Gray (95% confidence interval = 3.1–23.3%; p < 0.001). This rate was enhanced for ever smokers with an excess rate of 17.3% per Gray (95% CI = 4.5–54%; p < 0.005).

Conclusions

Second lung cancer after radiotherapy for early breast cancer is associated with the delivered dose to the lung. Although the absolute risk is relative low, the growing number of long-time survivors after breast cancer treatment highlights the need for advances in normal tissue sparing radiation techniques.