Mutagen sensitivity and risk of second cancer in younger adults with head and neck squamous cell cancer: 15-year results.

PURPOSE: To evaluate the mutagen sensitivity phenotype on the risk of second primary cancer (SPC) in patients with head and neck squamous cell carcinoma (HNSCC), and to estimate the long-term rate of SPC and the outcome with SPC. METHODS: A survey was made regarding SPC among 124 younger (≤ 50 years) adults with HNSCC who were enrolled in a pretreatment mutagen sensitivity investigation during 1996-2006. Mutagen sensitivity was assessed by exposing lymphocytes to bleomycin in vitro and quantifying the bleomycin-induced chromatid breaks per cell (b/c). Patients were classified as hypersensitive (> 1 b/c) or not hypersensitive (≤ 1 b/c). RESULTS: Mean follow-up time for all patients was 68 months (range: 5-288 months), and the 15-year cancer-specific survival was 15%. Twenty patients (16%) developed a SPC (15-year estimated rate: 41%), and half of them was hypersensitive. The crude rate of SPC for hypersensitive (n = 65) or not hypersensitive (n = 59) patients were 15 and 17%, respectively (p = 0.4272). The 15-year estimated rate of SPC for hypersensitive and not hypersensitive patients was 36 and 48%, respectively (p = 0.3743). Gender, UICC stages, anatomical sites of index cancer did not prove to be a significant risk factor for SPC. Forty-five percent of SPC developed after the 10-year follow-up. The 3­year cancer-specific survival was 23% with SPC. CONCLUSION: According to our findings, mutagen hypersensitivity was not associated with an increased SPC risk in HNSCC patients. Patients are at a lifelong risk of developing a SPC. Survival with SPC is very poor.

Dosimetric comparison between treatment plans of patients treated with low-dose-rate vs. high-dose-rate interstitial prostate brachytherapy as monotherapy: Initial findings of a randomized clinical trial.

PURPOSE: The aim of this study was to compare the dosimetry of intraoperative dose plans of prostate cancer patients treated with low-dose-rate (LDR) and high-dose-rate (HDR) interstitial brachytherapy (BT). METHODS AND MATERIALS: A randomized clinical trial was initiated at our institution to compare the results and side effects of LDR and HDR BT as monotherapy in the treatment of early, organ-confined prostate cancer patients. Eighty-seven patients were randomly assigned to receive HDR afterloading BT with one fraction of 19 Gy or permanent LDR 125I seed BT with 145 Gy. Inverse optimization algorithms were used for planning. Stranded seeds were implanted using live ultrasound imaging after preimplant treatment planning. Final dosimetry of HDR treatments was based on updated needle and contour positions. Statistical comparisons with nonparametric test were performed between the corresponding dose-volume parameters. RESULTS: The V100 and V150 were 99% and 61%, respectively, for LDR, whereas 98% and 32% for HDR treatments. The D90 was less for HDR (122% vs. 110%). The dose distributions were more homogeneous and conformal with HDR technique (dose homogeneity index, 0.39 vs. 0.67; conformal index, 0.65 vs. 0.80). The urethra and rectum received significantly less dose with HDR. The D10 and D30 for urethra were 133% and 128%, respectively, for LDR and 114% and 111% for HDR treatments. The [Formula: see text] for rectum was 68% and 55% for LDR and HDR technique, respectively. CONCLUSIONS: Both techniques provided acceptable target volume coverage with a slightly higher value with the LDR technique. The dose distributions were more homogeneous and conformal, and both urethra and rectum were better protected with the HDR technique.

Eight-year follow up result of the OTOASOR trial: The Optimal Treatment Of the Axilla - Surgery Or Radiotherapy after positive sentinel lymph node biopsy in early-stage breast cancer: A randomized, single centre, phase III, non-inferiority trial.

INTRODUCTION: The National Institute of Oncology, Budapest conducted a single centre randomized clinical study. The OTOASOR (Optimal Treatment Of the Axilla - Surgery Or Radiotherapy) trial compares completion of axillary lymph node dissection (cALND) to regional nodal irradiation (RNI) in patients with sentinel lymph node metastasis (pN1sn) in stage I-II breast cancer. PATIENTS AND METHODS: Patients with primary invasive breast cancer (cN0 and cT ≤ 3 cm) were randomized before surgery for cALND (standard treatment) or RNI (investigational treatment). Sentinel lymph nodes (SN) were investigated with serial sectioning at 0.5 mm levels by hematoxylin-eosin staining. Investigational treatment arm patients received 50 Gy RNI instead of cALND. Adjuvant treatment and follow up were performed according to the actual guidelines. Between August 2002 and June 2009, 1054 patients were randomized for cALND and 1052 patients for RNI. SN was evaluated in 2073 patients and was positive in 526 patients (25.4%). 474 cases were evaluable (244 in the cALND and 230 in the RNI arm), and in the cALND group 94 of 244 patients (38.5%) who underwent completion axillary surgery has additional positive nodes. The two arms were well balanced according to the majority of main prognostic factors. Primary endpoint was axillary recurrence and secondary endpoints were overall survival (OS) and disease-free survival (DFS). RESULTS: Mean follow-up was 97 months (Q1-Q3: 80-120). Axillary recurrence was 2.0% in cALND arm vs. 1.7% in RNI arm (p = 1.00). OS at 8 years was 77.9% vs. 84.8% (p = 0.060), and DFS was 72.1% in cALND arm and 77.4% after RNI (p = 0.51). The results show that RNI is statistically not inferior to cALND treatment. CONCLUSIONS: The long term follow-up results of this prospective-randomized trial suggest that RNI without cALND does not increase the risk of axillary failure in selected patients with early-stage invasive breast cancer (cT ≤ 3 cm, cN0) and pN1(sn). Axillary radiotherapy should be an alternative treatment for selected patients with sentinel lymph node metastases.

Dosimetric and radiobiological comparison of TG-43 and Monte Carlo calculations in 192Ir breast brachytherapy applications.

PURPOSE: To investigate the clinical significance of introducing model based dose calculation algorithms (MBDCAs) as an alternative to TG-43 in 192Ir interstitial breast brachytherapy. MATERIALS AND METHODS: A 57 patient cohort was used in a retrospective comparison between TG-43 based dosimetry data exported from a treatment planning system and Monte Carlo (MC) dosimetry performed using MCNP v. 6.1 with plan and anatomy information in DICOM-RT format. Comparison was performed for the target, ipsilateral lung, heart, skin, breast and ribs, using dose distributions, dose-volume histograms (DVH) and plan quality indices clinically used for plan evaluation, as well as radiobiological parameters. RESULTS: TG-43 overestimation of target DVH parameters is statistically significant but small (less than 2% for the target coverage indices and 4% for homogeneity indices, on average). Significant dose differences (>5%) were observed close to the skin and at relatively large distances from the implant leading to a TG-43 dose overestimation for the organs at risk. These differences correspond to low dose regions (<50% of the prescribed dose), being less than 2% of the prescribed dose. Detected dosimetric differences did not induce clinically significant differences in calculated tumor control probabilities (mean absolute difference <0.2%) and normal tissue complication probabilities. CONCLUSION: While TG-43 shows a statistically significant overestimation of most indices used for plan evaluation, differences are small and therefore not clinically significant. Improved MBDCA dosimetry could be important for re-irradiation, technique inter-comparison and/or the assessment of secondary cancer induction risk, where accurate dosimetry in the whole patient anatomy is of the essence.

A retrospective dosimetric comparison of TG43 and a commercially available MBDCA for an APBI brachytherapy patient cohort.

PURPOSE: To compare dosimetry using a contemporary model based dose calculation algorithm (MBDCA) following TG186 recommendations, and the conventional TG43 method in an (192)Ir high dose rate (HDR) accelerated partial breast irradiation (APBI) patient cohort. METHODS: Data of 38 APBI patients were studied. Dosimetry for the treatment plans was performed using both the TG43 and TG186 dose calculation methods of the Oncentra Brachy v4.4 treatment planning system (TPS). Analysis included indices of clinical interest for the planning target volume (PTV coverage, dose homogeneity, conformity) as well as dose volume histograms (DVH) for the breast, lung, heart, rib and skin. Significance testing of observed differences between TG43 and TG186 results was carried out and the effect of target location to these differences was studied. RESULTS: Statistically significant differences were observed in the values of clinically relevant DVH parameters for the PTV and the organs at risk (OAR), except for the heart. Differences for the PTV are relatively small (<1% for coverage, on the order of 2% for homogeneity and conformity) with a slight TG43 overestimation except for the dose homogeneity. Percentage differences are larger for the rib and lung (on the order of 4% for Dmax and 5% for V10Gy, respectively) and maximum for the skin (on the order of 6% for D10cc), with a correlation of the observed differences with target location. CONCLUSION: While the MBDCA option of the TPS appears to improve dosimetric accuracy, differences from TG43 do not appear to warrant dose prescription changes or treatment protocol amendment..

Cetuximab and platinum-based chemoradio- or chemotherapy of patients with epidermal growth factor receptor expressing adenoid cystic carcinoma: a phase II trial.

BACKGROUND: Epidermal growth factor receptor (EGFR) is highly expressed in adenoid cystic carcinoma (ACC). The efficacy and toxicity of cetuximab with concomitant platinum-based chemoradio- or chemotherapy in patients with locally advanced or metastatic ACC, respectively, was evaluated. METHODS: Eligible patients (9 with locally advanced tumour and 12 with metastases) had positive tumour EGFR expression. The cetuximab loading dose (400 mg m⁻²) was followed by 250 mg m⁻² per week. Locally advanced tumours were irradiated (mean dose 65 Gy) and treated with concomitant cisplatin (75 mg m⁻², intravenously). Patients with metastases received concomitant cisplatin and 5-fluorouracil (4 × 1000 mg m⁻²). RESULTS: For patients with locally advanced disease (median follow-up: 52 months), the median progression-free survival (PFS) was 64 months and the 2-year overall survival (OS) rate was 100%. For patients with metastases (median follow-up: 72 months), the median PFS and OS were 13 and 24 months, respectively. In both groups the objective response rate was >40%. Skin rash, in-field dermatitis, mucositis and vomiting were the most frequent grade 3/4 adverse events. CONCLUSION: In this single-arm study, the efficacy of cetuximab plus chemoradio- or chemotherapy appeared favourable as compared with historical controls. All side effects were manageable and did not hamper the treatment.

OECI Workshop on late side-effects of cancer treatments.

This Workshop was organised by the Organisation of European Cancer Institutes (OECI) to provide a forum for discussing the late side-effects resulting from different cancer treatments. One of the main Workshop objectives was to generate recommendations on how to improve knowledge and, consequently, long-term care for cancer survivors.

Prognosis of patients with local recurrence after mastectomy or conservative surgery for early-stage invasive breast cancer.

Between 1983 and 1987, 1309 women with stage I or II breast cancer underwent mastectomy (n=894) or conservative surgery (CS, n=415). Of these patients, 124 developed an isolated local recurrence (ILR): chest wall, 56 and in-breast, 68. The 10-year actuarial rate of cause-specific survival after treatment for ILR was 52%. On multivariate analysis three independent prognostic factors for the risk of death after ILR were identified: operability of recurrence (operable vs. inoperable, relative risk [RR]: 5.9), age at initial diagnosis (>40 vs. < or = 40 years, RR: 2.2) and time to ILR (>24 vs. < or = 24 months, RR: 2). Initial lymph node stage (negative vs. positive) showed borderline significance (p=0.06), and type of initial surgery (CS vs. mastectomy) and recurrent tumor grade (1-2 vs. 3) were not independent predictors of survival. In the mastectomy group, single surgical scar recurrence with initial node negative stage predicted good prognosis, and the 10-year survival was 85%. In the CS group, the 10-year survival rate was 88% with new primary tumor and 54% with true recurrence (p=0.01), and the type of salvage surgery (mastectomy vs. repeat complete excision) had no significant impact on survival (p=0.2). The majority (n=44) of CS patients developed < or = 2 cm in-breast recurrence, and the 10-year survival was 81% after both salvage excision (n=28) and mastectomy (n=16). The identified unfavorable prognostic factors are pointers of the forthcoming systemic progression. Patients with < or = 2 cm in-breast recurrence might receive a second CS.

Early European experience with the MammoSite radiation therapy system for partial breast brachytherapy following breast conservation operation in low-risk breast cancer.

Preliminary results of ultrasound studies do exist in the literature on the successful use of the MammoSite Radiation Therapy System (RTS), a new device for delivering brachytherapy following breast-conserving surgery. In Europe, some groups started a prospective multicentre trial to investigate the use of the MammoSite RTS. In this early publication, we analysed the surgical procedure and placement of the MammoSite, treatment planning and radiation delivery complications, and early cosmesis, as well as the comfort of the patients. Between June 2002 and March 2005, a total of 54 low-risk breast cancer patients fulfilling the enrolment criteria were implanted intra- or postoperatively using the MammoSite applicator. After inflating the balloon in the excision cavity, the reference isodose was defined 1cm from the balloon's surface. Twenty-eight patients were treated with primary brachytherapy with a total dose of 34 Gy (2x3.4 Gy) and 16 patients had a boost with a mean dose of 13.3 Gy (range: 7.5-15 Gy; 2x2.5 Gy) combined with external beam radiotherapy (EBRT). Doses ranged between 46 and 50 Gy. We analysed the postimplant anatomic position of the applicator in relation to the skin and chest wall as well as the geometric form of the balloon via ultrasound, computed tomography and X-ray before, during and after the treatment. Forty-four out of 54 patients (81.5%) were eligible for MammoSite RTS brachytherapy. Ten patients were excluded from the trial due to the strict study criteria and received no brachytherapy. Balloon rupture occurred in two cases. We observed seroma in 16 patients (36%); furthermore, an abscess developed in two patients (4.5%) within 3 months of implantation. Postoperative air gaps and haematoma were successfully reduced by draining the operation cavity in one institution. At a mean follow-up of 14 months (range 3-31 months), the skin-related side effects observed were skin discoloration or inflammation in 36 patients (82%) and teleangiectasia in eight patients (18%). The MammoSite RTS is a feasible treatment modality for postoperative partial breast irradiation after breast-conserving surgery for selected low-risk breast cancer patients. The main advantage of the system is the necessity of only one applicator for the delivery of fractionated radiotherapy over a 5-day treatment period. In addition, patient tolerance of the procedure is high. Based on this early experience, the method may serve as a successful alternative to conventional multicatheter brachytherapy for a highly select group of patients, but we have to bear in mind the higher level of acute toxicity.

The time-course of metastases from breast cancer after mastectomy and breast-conserving surgery with and without isolated local-regional recurrence.

We have examined time intervals between events in 390 metastatic breast cancer (MBC) patients whose distant failure developed within 10 years from initial surgery of Stage I/II disease. All of the patients underwent axillary dissection and mastectomy (n=295) or breast-conserving surgery (BCS, n=95), between 1983 and 1987. Distinctions have been made between distant failure with (n=79) and without (n=311) isolated local-regional recurrence (LRR). The median survival time after first relapse was significantly longer with intrabreast (30 months) and chest wall (24 months) than with distant relapse (15 months), but with axillary (17 months) or with supraclavicular (17 months) relapse survival was similar. The delay between LRR and distant metastasis was shorter with axillary (7 months) and supraclavicular (9 months) than with breast (20 months) and chest wall (12 months) recurrences. The median postmetastatic survival time by site of first relapse was significantly shorter with supraclavicular (6 months) and axillary (9 months) than with distant site relapse (15 months) but with intrabreast (12 months) or with chest wall (11 months) recurrence survival was similar. In MBC, regional recurrences are associated with a shorter interval between events than with local recurrences. The shortened intervals for patients with regional recurrence suggest that metastases existed at the time of initial surgery. The question of whether prevention of local or regional recurrence or both improves cause-specific survival after mastectomy or BCS needs to be answered in randomized studies.

[Management of the axilla in breast cancer: evidences and unresolved issues]. / Az axilla kezelése emlórákban: evidenciák és vitatott kérdések.

In this study the evidences governing the management of the axilla were examined and on the base of these evidences, the optimal clinical practice was outlined. Computerized searches for publications, debating specific treatment of axilla, were done of MEDLINE data. Level of evidence was determined using standard criteria: 1. metaanalysis of randomized trials, 2. randomized trial, 3. prospective and retrospective studies, 4. reports and opinion of expert committees and working teams. The probability of lymph node involvement is related directly to the size of the primary tumour, and even with small tumour (up to 10 mm), the risk of nodal metastases is in the order of 10-20%. To date, the best strategy for determining complete lymph node status (qualitative and quantitative information) is through axillary dissection. For an accurate staging, at least ten nodes have to be obtained. Formal axillary sampling does not provide total quantitative data in patients with involved axilla. Sentinel node biopsy is a promising alternative to axillary dissection for staging but it is still under way. Axillary dissection should be omitted in patients with ductal carcinoma in situ since the probability of nodal involvement is less than 1%. In invasive breast cancer, the risk of axillary recurrence in the untreated axilla varies from about 10% to 40%. For women with stage I-II breast cancer at least level I and II axillary node dissection should be offered as the standard procedure to reduce the risk of regional recurrence. Women at high risk of axillary recurrence (> or = 4 involved nodes, < 6 nodes were obtained from a positive axilla) will require axillary irradiation after axillary dissection. However, there is a lack of higher level evidence to support the benefit of post-dissection axillary irradiation. Evidences suggest that axillary irradiation is as effective as axillary dissection in preventing regional recurrence. The following factors have to be considered for decisions regarding dissection or irradiation: patient wishes, general condition, age, the necessity of pathological nodal status for systemic therapy and the risk of post-treatment morbidity. At this time, there is no well defined subgroup of patients in whom axillary intervention can be safely omitted. In selected patients with clinically negative axilla, the decision to observe the axilla rather than use surgery or irradiation should be made jointly between the women and her specialists (surgeon, radiation and medical oncologist). The benefits of axillary treatment in prolonging survival are unclear. Studies have reported different effects on survival. Until evidences remain insufficient, the risk of axillary recurrence has to be minimized, and more and more patients have to be provide to get treatments in randomized clinical trials. Patient should be fully informed about the benefits and the potential side effects of treatments. A combination of radiotherapy and axillary dissection results an increased morbidity rate compared with either alone.

[Breast-conserving treatment for early invasive lobular breast cancer: 15 years results]. / Emlómegtartó kezelés korai invazív lobularis emlórákban: 15 éves eredmények.

BACKGROUND: Infiltrating lobular cancer is biologically different from invasive ductal cancer and there is disagreement regarding appropriate local management of this disease. PURPOSE: To examine treatment outcomes after breast-saving surgery for patients with invasive lobular breast cancer. MATERIAL AND METHODS: Between 1983 and 1987, 77 women with early, stage I-II invasive lobular breast cancer were treated with complete gross excision of the tumour and axillary dissection. Fifty-eight of these patients were treated with 50 Gy ipsilateral breast irradiation, and 19 did not receive radiotherapy. During 176 month median follow-up local-regional recurrences, distant metastases, contralateral breast cancers, breast cancer deaths and deaths caused by other disease were scored. The probability of survival was estimated by Kaplan-Meier method. In uni- and multivariate analysis the Cox-model was used. Relative risk (RR) and associated confidence intervals (CI) were calculated from the regression coefficients. Statistical differences in proportions and means were assessed by log rank and Fisher exact-tests. RESULTS: In the saved breast, the actual rate of local recurrence at 15 years was 13% for irradiated and 53% for non-irradiated patients (RR: 0.1; 95% CI: 0.03-0.31; p: < 0.0001). The incidence of total breast cancer relapses (local-regional recurrences and distant metastases) was also higher for non-irradiated than for irradiated patients (74% vs. 40%; p: 0.0168). In multivariate analysis irradiation (no vs. yes) showed a significant effect on local tumour control (RR: 0.08: 95% CI: 0.02-0.28; p: 0.0001), but menopausal (pre vs. post), T-(T1 vs. T2) and N-(N0 vs. N1) status did not. The breast cancer specific survival at 15 years was 74% without and 62% with local recurrence (RR: 1.45; 95% CI: 0.53-3.96; p: 0.4697). The majority of local recurrences (9 of 14) were curable by salvage surgery. For all patients the rate of contralateral breast cancer was 6.5%. CONCLUSION: Results of long-term follow-up confirmed that breast-conserving surgery and radiotherapy is a reasonable treatment for patients with early invasive lobular breast cancer. The majority of local recurrences are curable by salvage surgery.

The role of STIR MRI sequence in the evaluation of the breast following conservative surgery and radiotherapy.

The purpose of the study was to define the value of fat suppressed STIR sequence in the MRI of the conserved breast. To our knowledge, this study is the first clinical evaluation of STIR sequence in post-therapy conditions. Forty patients with early (T1-2, N0-1) invasive breast cancer underwent conservative surgery and postoperative radiotherapy. Routine follow-up examinations, including physical examination and mammography were supplemented with breast MRI in all cases 6-166 months (mean 27.6) after initial treatments. Three patients had bilateral cancer. Including follow-up (9 patients) MRI examinations, altogether 53 MRIs were available for analysis. An 0.5 T MRI (Elscint, Haifa, Israel) was used with double breast coil. Axial T1 and T2 weighted spin echo, STIR and 3D gradient echo dynamic sequences were performed. Pre- and postcontrast slices underwent serial subtraction. Twenty-eight circumscribed lesions were identified. All were well visualised on STIR sequence, regardless of histologic nature of lesions. One low grade DCIS was not detected by any sequence. Differential diagnosis between benign and malignant lesions was not possible by STIR sequence alone. STIR sequence was found to be more sensitive in the detection of treatment related breast edema and fluid collection, than T2 SE (spin-echo) sequence. Even the patients who were not good candidates for subtracted contrast enhanced dynamic studies - because of motion artefacts - could have been examined with satisfactory results. STIR is a very sensitive sequence for depicting circumscribed lesions and post-therapy complications, but not suitable for differentiation. It is a useful tool in the follow-up of patients with conserved breast subjected to radiotherapy.

The importance of interstitial radiotherapy in the treatment of the base of tongue tumors: a retrospective analysis.

The authors have reviewed their experience with interstitial brachytherapy for the base of tongue cancer with the purpose of introducing treatment strategy and technique and presenting results. Between January 1993 and May 1999 twenty-one patients with primary squamous cell cancer of the base of tongue (T1-4N0-2) were treated by interstitial radiotherapy (RT). Seventeen patients with advanced stage cancer received brachytherapy (BT) boost after 60-66 Gy teletherapy and 4 patients with early stage (T1-2N0) were managed by sole BT after tumor excision and elective neck node dissection in case of positive or very narrow (< 5 mm) margin. High-dose rate (HDR) after-loading unit (Ir-192 source) was used with rigid needles or flexible plastic tubes. The treatment plan was performed by PLATO 3D BT planning system. The mean dose of boost BT or sole BT was 20 Gy (12-24 Gy) and 27 Gy (24-30 Gy), respectively. All treatments were delivered on consecutive days with a twice daily fractionation schedule, except the rigid needle technique (n = 4), where the dose was 12 Gy with a single fraction. After definitive RT of advanced stage disease, the rate of complete or partial remission was 65% (11/17) and 35% (6/17), respectively. At a mean follow-up time of 32 months the local tumor control for the entire patient population was 62% (13/ 21). Five patients (24%) died of local and/or regional failure and sixteen patients (76%) are alive (6 with local and/or regional disease and 10 without evidence of disease). All of the four sole BT treated patients belong to the latter group. The incidence of grade 2 or grade 3 mucositis was 48% and 52%, respectively. To achieve good local control with adequate doses, avoiding surgical morbidity and associated functional loss and to minimize late radiation sequelae, the combination of percutan and interstitial RT seems to be very advantageous in the treatment of the advanced tumor of the base of tongue. For patients with early stage (T1-2N0) cancer, sole postoperative BT of the tumor bed - by positive or very narrow margins - seems to be a feasible option. However, more patients and longer follow-up is required to define the value of sole BT.

Postirradiation angiosarcoma of the chest wall and breast: issues of radiogenic origin, diagnosis and treatment in two cases.

The authors report two cases of postradiation angiosarcoma (AS) among 5,100 breast cancer patients treated in the period 1980-1994 at the National Institute of Oncology, Budapest. Relevant data in the literature is also reviewed to analyze the questions of radiogenic origin, diagnosis and treatment. Secondary AS occurred in these cases in a previously irradiated field after a 6- and 8-year latency period, respectively. Detailed histopathological and immunohistochemical examinations from the biopsy specimens confirmed the diagnosis as AS. The first patient was treated successfully with radical surgery. The second patient, with unresectable AS, died of rapid local progression within 4 months. The incidence of chest wall and breast AS after radiotherapy was found to be 0.46 per 1,000 in our patient population, which means an estimated odds ratio of 2.9 for secondary AS. Patients treated with radiotherapy for primary breast cancer are at higher risk for developing secondary AS compared to the healthy population. An etiological relationship between radiotherapy and subsequent AS of the chest wall and breast is likely, but still controversial. Initial radical surgery is the only effective treatment for achieving long-term survival. These very rare cases deserve special attention due to the atypical clinical appearance, difficulties of differential diagnosis and poor prognosis.

The role of boost irradiation in the conservative treatment of stage I-II breast cancer.

In this article, we review the current status, indication, technical aspects, controversies, and future prospects of boost irradiation after breast conserving surgery (BCS). BCS and radiotherapy (RT) of the conserved breast became widely accepted in the last decades for the treatment of early invasive breast cancer. The standard technique of RT after breast conservation is to treat the whole breast up to a total dose of 45 to 50 Gy. However, there is no consensus among radiation oncologists about the necessity of boost dose to the tumor bed. Generally accepted criteria for identification of high risk subgroups, in which boost is recommended, have not been established yet. Further controversy exists regarding the optimal boost technique (electron vs. brachytherapy), and their impact on local tumor control and cosmesis. Based on the results of numerous retrospective and recently published prospective trials, the European brachytherapy society (GEC-ESTRO), as well as the American Brachytherapy Society has issued their guidelines in these topics. These guidelines will help clinicians in their medical decisions. Some aspects of boost irradiation still remain somewhat controversial. The final results of prospective boost trials with longer follow-up, involving analyses based on pathologically defined subgroups, will clarify these controversies. Preliminary results with recently developed boost techniques (intraoperative RT, CT-image based 3D conformal brachytherapy, and 3D virtual brachytherapy) are promising. However, more experience and longer follow-up are required to define whether these methods might improve local tumor control for breast cancer patients treated with conservative surgery and RT.

The impact of radiotherapy on the incidence and time of occurrence of local recurrence in early-stage breast cancer after breast conserving therapy.

There is still little information on the delay of local recurrence after conservatively treated and irradiation breast cancer. To evaluate the impact of radiation therapy (RT) on the incidence and on the time of occurrence of ipsilateral breast tumor recurrence (IBTR), we reviewed the treatment results in 415 women with UICC Stage I or II unilateral breast cancer. All underwent breast conserving surgery (BCS) and full axillary dissection between 1983 and 1987. Out of them 309 patients were irradiated and 106 were not. The median dose of RT was 50 Gy in five weeks to the whole breast. Systemic therapy, when it was given, consisted of 6-cycles of CMF for node positive premenopausal women and 20 mg tamoxifen for three years for postmenopausal women. The median follow up time was 120 months in survivors. The 10-year actuarial IBTR rate was 36.6% for the nonirradiated and 9.1% for the irradiated women (p = 0.0000); 48.6% for patients treated with CMF and 4.2% for those treated with CMF plus RT (p = 0.0051); 29.0% for patients treated with tamoxifen and 7.9% for those treated with tamoxifen plus RT (p = 0.0318). The patient's age and the presence of an extensive intraductal component (EIC) were both highly associated with the likelihood of tumor recurrence in the treated breast. Patients under 41 years of age had an actuarial 10-year IBTR rate of 75% without RT and 17. 1% with RT (p = 0.0006). Women with an EIC positive tumor had an IBTR rate of 88.9% when RT was not given and 27.2% when RT was given (p = 0.0003). In invasive lobular cancer, irradiated patients had a IBTR rate of 2.3%, compared to 53.2% for nonirradiated patients (p = 0.0008). RT resulted in a significant delay in the appearance of IBTR (p = 0.0250) and the median time was increased by 20.0 months. We conclude that RT has the property of not only preventing but also delaying IBTR. In invasive lobular tumors the risk of IBTR is very high when RT is omitted, but BCS plus radiation therapy is effective treatment. Patients wih EIC positive tumor are at high risk of IBTR even when a median dose of 50 Gy is given to the whole breast.