Breast-conserving treatment for ductal carcinoma in situ: Impact of boost and tamoxifen on local recurrences.

PURPOSE: Ductal carcinoma in situ represents 15 to 20% of all breast cancers. Breast-conserving surgery and whole breast irradiation was performed in about 60% of the cases. This study reports local recurrence rates in patients with ductal carcinoma in situ treated by breast-conserving surgery and whole breast irradiation with or without boost and/or tamoxifen and compares different therapeutic options in two European countries. PATIENTS AND METHODS: From 1998 to 2007, 819 patients with pure ductal carcinoma in situ were collected, both in France (266) and Italy (553). Median age was 56. All underwent breast-conserving surgery and whole breast irradiation; 391 (48%) received a boost (55% in France and 45% in Italy, P=0.017) and 173 (22.5%) tamoxifen (4.5% in France and 32% in Italy, P<0.0001). RESULTS: With a 90-month median follow-up, there were 51 local recurrences (6.2%), including 27 invasive (53%). The 5- and 10-year local recurrence rates were 4% and 8.6%. Two patients developed axillary recurrence and 12 (1.5%) metastases (seven after invasive local recurrence); 41 (5%) patients had contralateral breast cancer. In the multivariate analysis, high nuclear grade and lack of tamoxifen are the most powerful predictors of local recurrence, with 2.6 (95% confidence interval [95% CI]: 1.74-3.89, P=0.0012) and 2.85 (95% CI: 1.42-5.72, P=0.04) odds ratio (OR) estimates, respectively. Age, margin status and boost did not influence local recurrence rates. CONCLUSIONS: This study confirms the ductal carcinoma in situ treatment heterogeneity among countries and the unfavourable prognostic role of nuclear grade. Tamoxifen reduces local recurrence rates and might be considered for some subgroups of patients, but further confirmation is required. The boost usefulness still remains unclear.

Irradiation with standard tangential breast fields in patients treated with conservative surgery and sentinel node biopsy: using a three-dimensional tool to evaluate the first level coverage of the axillary nodes.

Recent data show that axillary coverage can be obtained, but only through a selective CT-based treatment planning, as standard tangential fields are inadequate to deliver therapeutic doses. Currently, the replacement of axillary dissection with new techniques, such as sentinel node (SN) biopsy, makes it necessary to re-address the question about the real role of axillary irradiation, complicated by the differences in the anatomy of dissected and undissected axillary regions. The purpose of this paper is the dosimetric analysis of first axillary level coverage in standard irradiation of 15 breast-cancer patients treated with quadrantectomy and SN biopsy (negative finding). During surgery a clip on the site of the SN was positioned, marking the caudal margin of first axillary level. After the breast treatment plan was completed, the first axillary level was contoured on CT scans, from the site of the surgical clip up to the sternal manubrium, for coverage analysis with dose-volume histograms (DVHs) and three-dimensional isodose visualization. The maximum dose mean ranged from 5% to 80% of the prescribed dose (mean value 48.7%). The mean total dose received by the volume of interest was lower than 40 Gy in all but one patient. No patient had total irradiation of first nodal level; only one patient had 35% of the volume enclosed in the 100% isodose. Our analysis lead to the conclusion that therapeutic doses are not really delivered to first level axillary level nodes by a standard tangential field technique, and that specific treatment planning and beam arrangement are required when adequate coverage is necessary.

Postmastectomy radiotherapy and concomitant adjuvant chemotherapy versus adjuvant chemotherapy alone in premenopausal breast cancer patients with positive axillary nodes.

AIMS: To evaluate the efficacy of postmastectomy radiotherapy (RT) combined with adjuvant chemotherapy compared to adjuvant chemotherapy alone as regards overall survival (OS), overall disease-free survival (ODFS), local disease-free survival (LDFS) and distant disease-free survival (DDFS). METHODS: We reviewed retrospectively two non-randomized groups of premenopausal high-risk breast cancer patients treated from 1985 to 1990 in the following Institutions: Department of Radiation Oncology of Brescia University, "Istituto del Radio O. Alberti" (IRA), and Department of Oncology of Brescia Hospital "Beretta Foundation" (BF). A total of 163 patients was found to satisfy the criteria of the current analysis: 81 patients received adjuvant chemotherapy alone [6 cycles CMF(1-8)] at BF and 82 patients received postoperative radiotherapy and chemotherapy [8 cycles CMF(1-21)] at IRA. A modified CMF schedule was chosen at IRA to avoid the feared increase in toxicity due to the association with RT. Primary surgical treatment was modified radical mastectomy with axillary node dissection in both cases. RESULTS: A statistically significant improvement in OS was found in systemic adjuvant therapy patients compared to those also given RT (77.6% vs 59%; P = 0.0025). No statistically significant improvement in ODFS was found in the CMF(1-8) arm compared to the RT and CMF(1-21) stm: 51.6% vs 43.6%; P = 0.46. A statistically significant improvement in LDFS at 5 years was found in irradiated patients (89.3% vs 76.2%; P <0.05). The DDFS was also improved, although without evidence of statistical significance, in the CMF(1-8) group: at 5 years 65% vs 44% (P = 0.059). CONCLUSIONS: The study confirmed that RT reduces the risk of local recurrence but without a statistically significant reduction in mortality. The lack of a survival benefit may somehow reflect the dose reduction in CMF(1-21). The evidence that CMF(1-8) offers undoubtable advantages over the CMF(1-21) regimen in OS and, perhaps, in distant control suggests that the dose intensity of CMF in this setting may also be important. In fact, although many CMF(1-8) patients received a dose intensity lower than 100%, 95% of them received a dose intensity higher than the maximum one of the CMF(1-21) patients. Although our results should be interpreted with caution, they seem to provide further rationale for testing the association of postoperative radiotherapy and the CMF(1-8) regimen in stage II breast cancer with positive nodes and treated with demolitive surgery, as already done in the conservative management of breast cancer, also in view of the new support therapies now available (i.e. hematologic growth factors).

[Management control and operative outcome of the Radio Institute "O. Alberti." Management of oncologic follow-up]. / Il controllo della gestione e il bilancio operativo dell'Istituto del Radio "O. Alberti". La gestione del follow-up oncologico.

Post-treatment cancer patient surveillance is an area with few given standards where the need of guidelines has become imperative with the recent emphasis on controlling the ever-increasing health care cost. Unfortunately, literature reports are often inconclusive and ambiguous, mostly because of the lack of properly controlled trials comparing the cost and benefits of various follow-up protocols. In addition, the actual impact on patient survival and quality of life is questionable. At the Istituto del Radio "O. Alberti" (IRA), we consider the follow-up as a sort of population screening aimed at the early detection and treatment of recurrent disease. While aggressive surveillance undoubtedly detects some cancers before symptoms develop, it is debated whether the impact on survival and quality of life are measurable. The early detection of relapse is only a potential survival benefit if recurrent disease is curable with further treatment or at least if salvage treatment is more effective in patients with less severe disease. We investigated the effectiveness, efficacy and medical care of our follow-up protocol. April to June, 1996, we examined 1,223 of 2,148 expected patients; 225 patients disattended the scheduled visits. IRA spent about It. L. 33,800 per examination. Fifty-seven patients were hospitalized to carry out treatment and IRA hospitalization charges were about It. L. 1,100,000 while overall social expenses were about It. L. 6,600,000. Regular visits to see an oncologist provide easy access to specialist medicine and convey a sense of being looked after with a caring system. 94.5% of patients prefers to continue the follow-up program with scheduled visits. Most patients (70%) know about the examinations they undergo but consistently overestimate the importance of laboratory tests and imaging findings and underestimate the importance of medical history and physical examination. In addition, most patients (95%) misinterpret the term "normal" relative to a test result. This study suggests that patients are unfamiliar with the limitations of more costly diagnostic and follow-up studies, which reflects the fact that physicians spend little time discussing follow-up strategies with their patients, especially regarding the cost-benefit analysis and the sensitivity and specificity of the laboratory tests and imaging examinations. Finally, in our opinion follow-up cost is acceptable even though expenses should be reduced optimizing the request of instrumental examinations. Therefore, oncologists should definitely try to inform their patients about the clinical importance of follow-up.

[Intracavitary brachytherapy in esophageal neoplasms. Experience at the Radiology Institute of Brescia]. / La brachiterapia endocavitaria nelle neoplasie esofagee. L'esperienza dell'istituto del Radio di Brescia.

We investigated the role of brachytherapy in the management of esophageal cancer. From March, 1990, to December 1994, seventy patients, with biopsy-proved esophageal carcinoma, were treated with brachytherapy +/- external beam radiotherapy. According to the TNM staging system, 24 patients were graded as T1, 24 as T2, 10 as T3, 9 as T4, and 3 as Tx. Median Karnofsky score was 80. Dysphagia was the major symptom in 68% of cases. Treatment consisted of low dose rate first, and then high dose rate brachytherapy, with progressive optimization of doses and fractions, up to total doses of 15-30 Gy in low dose rate and 7-21 Gy in high dose rate. When associated, external beam radiotherapy was delivered with conventional schedules. Tolerance to treatment was good with slight acute toxicity. Symptoms were markedly improved, with reduction of dysphagia in 100% of cases. Overall survival was 75%, 47%, 23% and 18% at 6, 12, 24, 36 months; no significant difference was found between low and high dose rate groups. Furthermore, no difference was shown in the overall survival of the group treated with brachytherapy alone and the one with associated external beam radiotherapy. Late toxicity occurred in 10% of patients and was managed by endoscopic procedures in all cases. In our opinion, brachytherapy appears to be an effective palliative treatment; its role as radical treatment remains to be defined.