Two-year clinical experience with tomotherapy: the French national cancer institute project on implementing new technology.

The pooled 2-year clinical experience using three tomotherapy units installed in France in 2007 is presented. Treatment indications and protocols were devised for each disease site and were the result of a consensus. A total of 642 patients were treated for central nervous system, head and neck, thoracic, abdominal, and pelvic tumors. Overall, grade 3, 4, and 5 acute toxicity was 10.7%, 0.3%, and 0.2%, respectively. Grade 3 chronic toxicity was 1.2%. There was no grade 4 or 5 chronic toxicity. The use of tomotherapy in a broad clinical practice is safe, and acute and chronic toxicity both are acceptable for all anatomical locations.

Preliminary experience of whole-brain radiation therapy (WBRT) in breast cancer patients with brain metastases previously treated with bevacizumab-based chemotherapy.

We report our experience of bevacizumab-based chemotherapy (BBCT) followed by whole-brain radiation therapy (WBRT) for breast cancer (BC) patients (pts) with inoperable brain metastases (BM) or who refused surgery. This is a retrospective study of seven metastatic BC pts treated at the Institut Curie with at least one course of BBCT before WBRT, with a delay of ≤ 12 months between the two treatments. Toxicity was scored according to the common terminology criteria for adverse events (v4. 2010). Median age was 56 years (41-65). Median follow-up was 5.9 months (0.4-24.6). The median dose of bevacizumab was 10 mg/kg. Median number of cycles BBCT was six (5-17). Different chemotherapy regimens were used, the most common combination was paclitaxel-bevacizumab. WBRT was delivered in ten fractions, five fractions/week, for two weeks, to a total of 30 Gy. One pt underwent stereotactic radio surgery (SRS) after WBRT. No pt received BBCT during RT. Most common reported side-effects were nausea (n = 4), headache (n = 3), vomiting (n = 1), and vertigo (n = 3). All pts had mild or moderate grade ≤ 2 neurologic toxicity. There were no radiological signs of necrosis or cerebral ischemia. BBCT before WBRT was not associated with severe brain toxicity. Because of the limited number of pts, the different BBCT regimens, and important delays between treatments, these results must be confirmed prospectively.

Management of operable invasive breast cancer in women over the age of 70: long-term results of a large-scale single-institution experience.

BACKGROUND: The treatment of choice for elderly women with breast cancer remains controversial. This retrospective analysis of a cohort from a single institution was designed to evaluate whether such patients are really undertreated because of their age and to reappraise their usual management. METHODS: The characteristics of 538 patients aged > or = 70 years with operable breast cancer, treated between 1995 and 1999, were retrospectively analyzed comparing patients aged 70 to 75 years (group I, n = 288), 75 to 80 years (group II, n = 156), and > or = 80 years (group III, n = 94). Cause-specific survival, distant recurrence-free interval, and local control were estimated by the Kaplan-Meier method and compared by log rank test. Multivariate analysis used Cox regression. RESULTS: In group III, tumors were more frequently T2 than T1 (P < 0.0001) and estrogen receptor negative (P = 0.045) than in groups I and II. Surgery was performed in 94.6% of patients, breast-conserving in 72.1% (62% in group III; P = 0.0015) with axillary dissection in 89.2% (77% in group III; P = 0.0015); 100% received radiotherapy after lumpectomy (hypofractionated in 63% of group III; P < 0.0001). Adjuvant hormone therapy and chemotherapy were administered to 57 and 3.7% of patients, respectively. At 7 years, no difference in the three groups was observed for cause-specific survival (91% for group I, 89% for group II, 86% for group III) distant recurrence-free interval, and local control (>90%). CONCLUSIONS: Elderly patients with operable breast cancer who are completely and correctly treated with realistic treatment options that are based on surgery and adjuvant radiotherapy have a similar chance of being cured as younger patients.

Concurrent capecitabine and whole-brain radiotherapy for treatment of brain metastases in breast cancer patients.

Preclinical data have demonstrated that ionizing radiation acts synergistically with capecitabine. This report retrospectively assessed the use of capecitabine concurrently with whole-brain radiotherapy (WBRT) in patients with brain metastases from breast cancer. From January 2003 to March 2005, five breast cancer patients with brain metastases were referred for WBRT with concurrent capecitabine. Median age was 44 years (range: 38-53). The median dose of capecitabine was 1,000 mg/m(2) twice daily for 14 days (day1-14). Treatment cycles were repeated every 21 days, concurrently with WBRT (30 Gy, 3 Gy per fraction, 5 days per week). Median survival after starting WBRT plus capecitabine was 6.5 months (range 1-34 months). One patient achieved a complete response. Two patients achieved partial response, including one with local control lasting until most recent follow-up. One patient had stable disease. The remaining patient was not assessable for response because of early death. Most commonly reported adverse events were nausea (n = 2) and headache (n = 2), always grade 1. Other toxicities were grade 3 hand/foot syndrome (n = 1), moderate anemia requiring transfusion and dose reduction of capecitabine (n = 1), and grade 1 mucositis (n = 1). Although promising, these preliminary data warrant further assessment of capecitabine-based chemoradiation in brain metastases from breast cancer and need to be further validated in the setting of a clinical trial.

Solitary plasmocytoma: improvement in critical organs sparing by means of helical tomotherapy.

PURPOSE: Helical tomotherapy (HT) was assessed in two patients with paramedullar solitary bone plasmocytoma. We compared doses delivered to critical organs, according HT plan or tridimensional conformal plan. METHODS AND MATERIALS: One male (patient no. 1), 67 yr-old and one female (patient no. 2), 37-yr-old, with histologically, biologically and radiological confirmed paramedullar solitary plasmocytoma have been treated in our department between November 2007 and February 2008 using HT. The prescription dose was 40 Gy in 20 fractions. This HT treatment planning was compared with a routine dosimetric work that was executed for a standard conformal radiotherapy treatment planning. RESULTS: Treatment tolerance was excellent, without any side effects. Both patients achieved 9-month complete remission. HT resulted in substantial critical organs sparing. For patient no. 1, dose delivered to 20% of the total intestine volume was reduced from 28 Gy for conformal radiotherapy to 13 Gy for HT. Radiation dose delivered to 20% of the left kidney was reduced from 25 Gy to 7 Gy. For patient no. 2, volume of left lung that received at least 20 Gy was 12% for conformal radiotherapy vs. 6% for HT. CONCLUSIONS: For paramedullar solitary plasmocytoma, HT has the potential to significantly improve the quality of the dose distribution both in terms of better dose homogeneity within the planning target volume and more efficient sparing of critical organs.

How to boost the breast tumor bed? A multidisciplinary approach in eight steps.

PURPOSE: To describe a new procedure for breast radiotherapy that will improve tumor bed localization and radiotherapy treatment using a multidisciplinary approach. PATIENTS AND METHODS: This pilot study was conducted by departments of radiation oncology, surgery, and radiology. A new procedure has been implemented, summarized as eight steps: from pre-surgery contrast CT to surgery, tumor bed planning target volume (PTV) determination, and finally breast and tumor bed irradiation. RESULTS: Twenty patients presenting with T1N0M0 tumors were enrolled in the study. All patients underwent lumpectomy with the placement of surgical clips in the tumor bed region. During surgery, 1 to 5 clips were placed in the lumpectomy cavity before the plastic procedure. All patients underwent pre- and postoperative CT scans in the treatment position. The two sets of images were registered with a match-point registration. All volumes were contoured and the results evaluated. The PTV included the clips region, the gross tumor volume, and the surgical scar, with an overall margin of 5-10 mm in all directions, corresponding to localization and setup uncertainties. For each patient the boost PTV was discussed and compared with our standard forward-planned PTV. CONCLUSIONS: We demonstrate the feasibility of a tumor bed localization and treatment procedure that seems adaptable to routine practice. Our study shows the advantages of a multidisciplinary approach for tumor bed localization and treatment. The use of more than 1 clip associated with pre- to postoperative CT image registration allows better definition of the PTV boost volume.

Postmastectomy electron beam chest wall irradiation in women with breast cancer: a clinical step toward conformal electron therapy.

PURPOSE: Electron beam radiotherapy of the chest wall with or without lymph node irradiation has been used at the Institut Curie for >20 years. The purpose of this report was to show the latest improvements of our technique developed to avoid hot spots and improve the homogeneity. METHODS AND MATERIALS: The study was split into two parts. A new electron irradiation technique was designed and compared with the standard one (dosimetric study). The dose distributions were calculated using our treatment planning software ISIS (Technologie Diffusion). The dose calculation was performed using the same calculation parameters for the new and standard techniques. Next, the early skin toxicity of our new technique was evaluated prospectively in the first 25 patients using Radiation Therapy Oncology Group criteria (clinical study). RESULTS: The maximal dose found on the five slices was 53.4 +/- 1.1 Gy for the new technique and 59.1 +/- 2.3 Gy for the standard technique. The hot spots of the standard technique plans were situated at the overlap between the internal mammary chain and chest wall fields. The use of one unique field that included both chest wall and internal mammary chain volumes solved the problem of junction. To date, 25 patients have been treated with the new technique. Of these patients, 12% developed Grade 0, 48% Grade 1, 32% Grade 2, and 8% Grade 3 toxicity. CONCLUSIONS: This report describes an improvement in the standard postmastectomy electron beam technique of the chest wall. This new technique provides improved target homogeneity and conformality compared with the standard technique. This treatment was well tolerated, with a low rate of early toxicity events.

Age remains the first prognostic factor for loco-regional breast cancer recurrence in young (<40 years) women treated with breast conserving surgery first.

PURPOSE: To ascertain the loco-regional recurrence (LRR) rate and its major prognostic factors in patients younger than 40 and to determine the influence of age on the features of breast cancer and its treatment in two age groups: 35 years and [36-39] years. METHODS AND MATERIALS: Between 1985 and 1995, 209 premenopausal women, younger than 40, were treated for early breast cancers with primary breast conserving surgery followed by radiotherapy+/-chemotherapy. Median age was 37 years with 66 patients (32%) 35 years and 143 older (68%). Median follow-up was 12 years. Tumours' characteristics were: cT1 in 75%, pN0 in 60%. RESULTS: LRR rate was 38% at 10 years, contralateral breast cancer rate 12%. Age was the only prognostic factor for LRR. The relative risk of LRR increased by 7% for every decreasing year of age. The annual risk of local recurrence peaked between 2 and 3 years after the initial diagnosis and returned to the level of contra-lateral breast cancer at 10 years. The younger population had infiltrating carcinomas that were significantly more commonly ductal, less commonly lobular, and of higher grade - they received chemotherapy more often. CONCLUSION: Using conventional methods we could find no explanation as to why age remained the most important prognostic factor for breast cancer LRR. Known prognostic factors such as involved surgical margins seemed erased by adequate radiotherapy doses.

Responses to concurrent radiotherapy and hormone-therapy and outcome for large breast cancers in post-menopausal women.

INTRODUCTION: This study aimed to evaluate responses and outcome of hormone-therapy (HT) and radiotherapy (RT) given concurrently for large breast cancers in post-menopausal women. MATERIAL AND METHODS: Forty-two breast carcinomas in 41 women were treated with HT and concurrent RT to the breast +/- lymph node bearing areas. For 30 tumours this was followed by breast surgery (with axillary lymph node dissection when the axilla had not been irradiated). RT delivered a median dose to the tumour of 50 Gy (48-66) and 75 Gy (65-84) for, respectively, preoperative and exclusive RT-HT. Median follow-up was 64 months. RESULTS: Out of 42 clinically assessable tumours (after a mean dose of 50 Gy), 9 tumours (21%) had complete clinical responses, 24 (57%) partial responses, 9 (21%) stable disease. Breast-conserving surgery or exclusive RT-HT was possible in 74% of tumours. For 29 patients who underwent breast surgery, the rate of pathological complete responses was 17%. At 50 Gy no skin toxicity higher than grade 2 occurred. Five year OS, RFS and local control were, respectively, 85%, 84% and 97%. Lymphoedema occurred in one patient. CONCLUSION: Concurrent association of RT-HT demonstrated good efficacy, both in terms of clinical and pathological complete responses. It allowed breast conservation with acceptable tolerance and good 5-year local control.

Whole breast radiotherapy in the lateral isocentric lateral decubitus position: Long-term efficacy and toxicity results.

PURPOSE: To evaluate previously published whole breast radiotherapy (WBRT) using ILD (isocentring lateral decubitus) technique in terms of toxicity and efficacy. MATERIALS AND METHODS: From 2006 to 2010, 832 female patients with early-stage breast cancer (BC) treated by conservative surgery underwent 3D-conformal WBRT-ILD at Institut Curie. The acute toxicity of treatment was evaluated weekly and the late toxicity (6months and later after the treatment) was evaluated every 6months till the 5th year after the end of the radiotherapy using NCI CTC v3.0 scale. Dosimetric study was performed to analyse the mean cardiac dose and the mean homolateral and contralateral lung doses. RESULTS: The median follow up was 6.4years. The median age was 61.5years (range, 29-90), and median body mass index (BMI) was 26.3. Fifty one percent of the patients presented left sided BC and 49% right sided. Different type of fractions were used: 46.5% of pts.: 50 (breast)+16Gy (boost) in 33fractions (fr), in 17.9%-50Gy/25fr, in 26.1%-40/15fr or 41.6Gy/13fr and in 9.5%: 30Gy/5fr. Acute dermatitis was present in 93% with a median of apparition of 4weeks, and only 2,8% grade 3. In multivariate analysis, the cup size had significant influence (p=0.0004) and the fractionation had a significative influence (p=0.0001). In the all patients' population, 94.1% of cases had no skin toxicity at 1year. No cardiac or pulmonary toxicity was reported. The median overall survival had not been reached at the end of follow-up. We observed 36 (3.6%) recurrences, as following: 30 local (breast) recurrences, 4 lymph node (LN), and 2pts experiencing both. CONCLUSION: Whole breast radiotherapy in the lateral decubitus position provides excellent results in terms of local control and survival. ILD is well tolerated with very good acute toxicity profile. No cardiac or pulmonary toxicity were observed in this study. Longer follow-up is needed to confirm these results.

Long-Term Results of a Highly Performing Conformal Electron Therapy Technique for Chest Wall Irradiation After Mastectomy.

PURPOSE: To evaluate locoregional control and survival after mastectomy, as well as toxicity, in patients irradiated by a previously described postmastectomy highly conformal electron beam radiation therapy technique (PMERT). METHODS AND MATERIALS: We included all women irradiated by postmastectomy electron beam radiation therapy for nonmetastatic breast cancer between 2007 and 2011 in our department. Acute and late toxicities were retrospectively assessed using Common Terminology Criteria for Adverse Events version 3.0 criteria. RESULTS: Among the 796 women included, 10.1% were triple-negative, 18.8% HER2-positive, and 24.6% received neoadjuvant chemotherapy (CT). Multifocal lesions were observed in 51.3% of women, and 64.6% had at least 1 involved lymph node (LN). Internal mammary chain, supraclavicular, infraclavicular, and axillary LNs were treated in 85.6%, 88.3%, 77.9%, and 14.9% of cases, respectively. With a median follow-up of 64 months (range, 6-102 months), 5-year locoregional recurrence-free survival and overall survival were 90% (95% confidence interval 88.1%-92.4%) and 90.9% (95% confidence interval 88.9%-93%), respectively. Early skin toxicity was scored as grade 1 in 58.5% of patients, grade 2 in 35.9%, and grade 3 in 4.5%. Concomitant CT was associated with increased grade 3 toxicity (P<.001). At long-term follow-up, 29.8% of patients presented temporary or permanent hyperpigmentation or telangiectasia or fibrosis (grade 1: 23.6%; grade 2: 5.2%; grade 3: 1%), with higher rates among smokers (P=.06); 274 patients (34.4%) underwent breast reconstruction. Only 24 patients (3%) had early esophagitis of grade 1. Only 3 patients developed ischemic heart disease: all had been treated by anthracycline-based CT with or without trastuzumab, all had been irradiated to the left chest wall and LN, and all presented numerous cardiovascular risk factors (2-4 factors). CONCLUSIONS: This study demonstrated the good efficacy of this technique in terms of locoregional control and survival, and good short-term and long-term safety. Longer follow-up is required to analyze chronic cardiac events.

Medico-economic impact of MSKCC non-sentinel node prediction nomogram for ER-positive HER2-negative breast cancers.

BACKGROUND: Avoiding axillary lymph node dissection (ALND) for invasive breast cancers with isolated tumor cells or micrometastatic sentinel node biopsy (SNB) could decrease morbidity with minimal clinical significance. PURPOSE: The aim of this study is to simulate the medico-economic impact of the routine use of the MSKCC non-sentinel node (NSN) prediction nomogram for ER+ HER2- breast cancer patients. METHODS: We studied 1036 ER+ HER2- breast cancer patients with a metastatic SNB. All had a complementary ALND. For each patient, we calculated the probability of the NSN positivity using the MSKCC nomogram. After validation of this nomogram in the population, we described how the patients' characteristics spread as the threshold value changed. Then, we performed an economic simulation study to estimate the total cost of caring for patients treated according to the MSKCC predictive nomogram results. RESULTS: A 0.3 threshold discriminate the type of sentinel node (SN) metastases: 98.8% of patients with pN0(i+) and 91.6% of patients with pN1(mic) had a MSKCC score under 0.3 (false negative rate = 6.4%). If we use the 0.3 threshold for economic simulation, 43% of ALND could be avoided, reducing the costs of caring by 1 051 980 EUROS among the 1036 patients. CONCLUSION: We demonstrated the cost-effectiveness of using the MSKCC NSN prediction nomogram by avoiding ALND for the pN0(i+) or pN1(mic) ER+ HER2- breast cancer patients with a MSKCC score of less than or equal to 0.3.

Pathological response to preoperative concurrent chemo-radiotherapy for breast cancer: results of a phase II study.

This study evaluated, in terms of pathological complete response (pCR) and acute toxicity, preoperative concurrent (5-fluorouracil (5-FU)-vinorelbine) chemoradiotherapy for large breast cancers. A total of 60 women were included in the study. Chemotherapy consisted of 4 cycles of 5-FU, 500 mg/m2/d, continuous infusion (d1-d5) and vinorelbine, 25 mg/m2 (d1; d6). Starting with the second cycle, radiotherapy delivered 50 Gy to the breast and 46 Gy to the internal mammary and supra/infra-clavicular lymph nodes. Breast surgery and axillary lymph node dissection were then performed. Four patients did not complete their chemotherapy. Breast conservation was possible in 69% of patients. The rate of pCR was 27%. Three factors were associated with pCR: histological grade 3, absence of hormonal receptors and high mitotic index. Grade 4 haematological toxicity occurred in 22% of patients. In conclusion, chemoradiotherapy demonstrated good efficacy, both in terms of pCR and in allowing breast conservation with acceptable tolerance.

CT-scan based localization of the internal mammary chain and supra clavicular nodes for breast cancer radiation therapy planning.

BACKGROUND AND PURPOSE: To evaluate the influence of the position and the exact localizations of supra clavicular nodes (SCN) and internal mammary chain (IMC) and their variability among patients in order to improve treatment planning in breast cancer (BC) patients. PATIENTS AND METHODS: A total of 46 CT scans of the chest were examined. All patients were female treated with breast conserving surgery and radiotherapy. The study was divided into two phases. The first consisted of measurements on 20 diagnostic CT scans, performed in the supine position with both arms over the head. All patients received contrast. This first phase was performed as a training program for radiologist and radiation oncologist to prepare for the second phase of the study: 26 CT scans in treatment position on angled board without injection. For this second group, patients had one arm raised above the head (treated side) and the other kept by the side (contralateral side). Measurements were performed on both sides to evaluate the influence of the arm position. The depths of IM- and SC vessels were measured at five points: (1) the origin of the internal mammary artery, (2) the sterno-clavicular articulation, (3-5) the first, second and third rib interspaces (RI). Measurements of the depth and of the distance between the internal mammary vessels and the middle axis of the sternum were obtained using electronic calipers on a PACS workstation. RESULTS: There were important individual variations of the depth of SCN, as follows: 20-84 mm (diagnostic) and 19-64 (treatment position). No differences in the depth of the IMC were found between treated and contralateral side at the region of the I, II, and III rib interspaces. The lateral margin of the IMC was never more than 40 mm from the middle axis of the sternum (I, II, III rib interspaces). There was no difference in the lateral limits of IMC (the distance between the IM vessels and the middle axis of the sternum) between the two sides: treated and contralateral. CONCLUSIONS: This study shows the importance of the patients' individual anatomy, their position and the large variability in the depth of SCN. It is important to visualize these regions to permit individual dosimetric optimization.

Helical tomotherapy and volumetric modulated arc therapy: New therapeutic arms in the breast cancer radiotherapy.

AIM: To analyse clinical and dosimetric results of helical tomotherapy (HT) and volumetric modulated arc therapy (VMAT) in complex adjuvant breast and nodes irradiation. METHODS: Seventy-three patients were included (31 HT and 42 VMAT). Dose were 63.8 Gy (HT) and 63.2 Gy (VMAT) in the tumour bed, 52.2 Gy in the breast, 50.4 Gy in supraclavicular nodes (SCN) and internal mammary chain (IMC) with HT and 52.2 Gy and 49.3 Gy in IMC and SCN with VMAT in 29 fractions. Margins to particle tracking velocimetry were greater in the VMAT cohort (7 mm vs 5 mm). RESULTS: For the HT cohort, the coverage of clinical target volumes was as follows: Tumour bed: 99.4% ± 2.4%; breast: 98.4% ± 4.3%; SCN: 99.5% ± 1.2%; IMC: 96.5% ± 13.9%. For the VMAT cohort, the coverage was as follows: Tumour bed: 99.7% ± 0.5%, breast: 99.3% ± 0.7%; SCN: 99.6% ± 1.4%; IMC: 99.3% ± 3%. For ipsilateral lung, Dmean and V20 were 13.6 ± 1.2 Gy, 21.1% ± 5% (HT) and 13.6 ± 1.4 Gy, 20.1% ± 3.2% (VMAT). Dmean and V30 of the heart were 7.4 ± 1.4 Gy, 1% ± 1% (HT) and 10.3 ± 4.2 Gy, 2.5% ± 3.9% (VMAT). For controlateral breast Dmean was 3.6 ± 0.2 Gy (HT) and 4.6 ± 0.9 Gy (VMAT). Acute skin toxicity grade 3 was 5% in the two cohorts. CONCLUSION: HT and VMAT in complex adjuvant breast irradiation allow a good coverage of target volumes with an acceptable acute tolerance. A longer follow-up is needed to assess the impact of low doses to healthy tissues.

Axillary treatment in conservative management of operable breast cancer: dissection or radiotherapy? Results of a randomized study with 15 years of follow-up.

PURPOSE: Axillary dissection is the standard management of the axilla in invasive breast carcinoma. This surgery is responsible for functional sequelae and some options are considered, including axillary radiotherapy. In 1992, we published the initial results of a prospective randomized trial comparing lumpectomy plus axillary radiotherapy versus lumpectomy plus axillary dissection. We present an update of this study with a median follow-up of 180 months (range, 12 to 221 months). PATIENTS AND METHODS: Between 1982 and 1987, 658 patients with a breast carcinoma less than 3 cm in diameter and clinically uninvolved lymph nodes were randomly assigned to axillary dissection or axillary radiotherapy. All patients underwent wide excision of the tumor and breast irradiation. RESULTS: The two groups were similar for age, tumor-node-metastasis system stage, and presence of hormonal receptors; 21% of the patients in the axillary dissection group were node-positive. Our initial results showed an increased survival rate in the axillary dissection group at 5 years (P =.009). At 10 and 15 years, however, survival rates were identical in both groups (73.8% v 75.5% at 15 years). Recurrences in the axillary node were less frequent in the axillary dissection group at 15 years (1% v 3%; P =.04). There was no difference in recurrence rates in the breast or supraclavicular and distant metastases between the two groups. CONCLUSION: In early breast cancers with clinically uninvolved lymph nodes, our findings show that long-term survival does not differ after axillary radiotherapy and axillary dissection. The only difference is a better axillary control in the group with axillary dissection.

Salvage treatment for local or local-regional recurrence after initial breast conservation treatment with radiation for ductal carcinoma in situ.

The present study evaluated the outcome of salvage treatment for women with local or local-regional recurrence after initial breast conservation treatment with radiation for mammographically detected ductal carcinoma in situ (DCIS; intraductal carcinoma) of the breast. The study cohort consisted of 90 women with local only first failure (n=85) or local-regional only first failure (n=5). The histology at the time of recurrence was invasive carcinoma for 53 patients (59%), non-invasive carcinoma for 34 patients (38%), angiosarcoma for one patient (1%), and unknown for two patients (2%). The median follow-up after salvage treatment was 5.5 years (mean=5.8 years; range=0.2-14.2 years). The 10-year rates of overall survival, cause-specific survival, and freedom from distant metastases after salvage treatment were 83%, 95%, and 91%, respectively. Adverse prognostic factors for the development of subsequent distant metastases after salvage treatment were invasive histology of the local recurrence and pathologically positive axillary lymph nodes. These results demonstrate that local and local-regional recurrences can be salvaged with high rates of survival and freedom from distant metastases. Close follow-up after initial breast conservation treatment with radiation is warranted for the early detection of potentially salvageable local and local-regional recurrences.

Breast radiotherapy in the lateral decubitus position: A technique to prevent lung and heart irradiation.

PURPOSE: To present an original technique for breast radiotherapy, with the aim of limiting lung and heart irradiation, satisfying quality assurance criteria. METHODS AND MATERIAL: An original radiotherapy technique for breast irradiation has been developed at the Institute Curie in January 1996. It consists of isocentric breast irradiation in the lateral decubitus position (isocentric lateral decubitus [ILD]). This technique is indicated for voluminous or pendulous breasts needing breast irradiation only. Thin carbon fiber supports and special patient positioning devices have been developed especially for this technique. In vivo measurements were performed to check the dose distribution before the routine use of the technique. RESULTS: ILD has been successfully implemented in routine practice, and 500 patients have been already treated. Breast radiotherapy is performed using a dose of 50 Gy at ICRU point in 25 fractions. ILD shows good homogeneity of the dose in breast treatment volume, treatment fields are perpendicular to the skin ensuring its protection, and extremely low dose is delivered to the underlying lung and heart. CONCLUSION: In cases of voluminous breasts or patients with a history of lung and heart disease, our technique provides several advantages over the conventional technique with opposing tangential fields. This technique improves the dose homogeneity according to the ICRU recommendations.

Proliferation markers predictive of the pathological response and disease outcome of patients with breast carcinomas treated by anthracycline-based preoperative chemotherapy.

The cell proliferation rate has been correlated to the response of breast carcinomas to preoperative chemotherapy (CT) and to disease outcome. However, this parameter is not yet used to select which tumours should be treated with preoperative CT. Furthermore, there is no consensus in the method used to evaluate cell proliferation. In poor prognosis breast carcinomas (PPBCs) treated by intensive preoperative CT, we compared the predictive value of S phase fraction (SPF), mitotic index (MI) and Ki67. We also evaluated the prognostic significance of the variation of the MI after CT. A series of 55 T2-T4N0N1M0 breast carcinomas were treated with 4 cycles of cyclophosphamide, 5-fluorouracil (5-FU) and doxorubicin. SPF was determined by flow cytometry on pre-therapeutic needle aspiration products. MI and Ki67 were evaluated on pre-therapeutic biopsy samples and on the tumours after CT. Fifteen patients (27%) had a pathological complete response (pCR), whereas 40 (73%) had residual disease. All three proliferative markers were found to have predictive value, but this value was higher for MI than for SPF (P = 0.04) and Ki67 (P = 0.03): the rate of pCR was 50% in cases with MI > 17/3.3 mm2, but was only 7% in cases with MI under this threshold (P = 0.0003). A significant decrease of MI (mean 10.97) was observed after CT (P = 0.001). Furthermore, we observed that even for patients with residual tumour, the variation of MI after CT was a prognostic parameter and overall survival. The sequential analysis of MI in breast cancers treated by preoperative CT thus provides a surrogate for predicting long-term outcome.