Maria Cristina Leonardi

Breast carcinoma in elderly women: Features of disease presentation, choice of local and systemic treatments compared with younger postmenopausal patients

Aging remains one of the single greatest risk factors for the development of new breast carcinoma. The aim of the study was to evaluate the relation between biologic features at first diagnosis of breast carcinoma and treatment choice for postmenopausal women ≥ 50 years to optimize treatment in the elderly.

Full-Dose Intraoperative Radiotherapy With Electrons During Breast-Conserving Surgery: Experience With 590 Cases

Background:Previous studies show that local recurrences after breast-conserving treatment occur in the site of the primary tumor. The need for postoperative radiotherapy on the whole breast is challenged in favor of radiotherapy limited to the area of the breast at high risk of recurrence. The new mobile linear accelerators easily moved close to the operating table to allow the full-dose irradiation during surgery. Patients and Methods:From July 1999 to December 2003, 590 patients affected by unifocal breast carcinoma up to a diameter of 2.5 cm received wide resection of the breast followed by intraoperative radiotherapy with electrons (ELIOT). Most patients received 21 Gy intraoperatively, biologically equivalent to 58 to 60 Gy in standard fractionation. Patients were evaluated 1, 3, 6, and 12 months after surgery, and thereafter every 6 months, to look for early, intermediate, late complications, and other events. Results:After a follow-up from 4 to 57 months (mean, 24 months; median, 20 months), 19 patients (3.2%) developed breast fibrosis, mild in 18, severe in 1, which resolved within 24 months. Three patients (0.5%) developed local recurrences, 3 patients ipsilateral carcinomas in other quadrants and other 5 patients contralateral breast carcinoma. One patient (0.2%) died of distant metastases. Conclusions:ELIOT is a safe method for treating conservatively operated breasts, avoids the long period of postoperative radiotherapy, and reduces drastically the cost of radiotherapy. ELIOT reduces radiation to normal tissues and organs. Results on short-term and middle-term toxicity up to 5 years of follow-up are good. Data on local control are encouraging.

How Do the ASTRO Consensus Statement Guidelines for the Application of Accelerated Partial Breast Irradiation Fit Intraoperative Radiotherapy? A Retrospective Analysis of Patients Treated at the European Institute of Oncology

PURPOSE To verify how the classification according to the American Society for Therapeutic Radiation Oncology (ASTRO) consensus statement (CS) for the application of accelerated partial breast irradiation (APBI) fits patients treated with intraoperative radiotherapy with electrons (ELIOT) at a single institution. METHODS AND MATERIALS The study included 1,822 patients treated with ELIOT as the sole radiation modality outside of a clinical trial at the European Institute of Oncology after breast-conserving surgery for invasive breast cancer, who were classified into CS groups of suitable, cautionary, and unsuitable. The outcome in terms of ipsilateral breast recurrence, regional node relapse, distant metastases, progression free-survival, cause-specific survival, and overall survival were assessed. RESULTS All the 1,822 cases except for 25 could be classified according to ASTRO CS: 294 patients met the criteria for inclusion into the suitable group, 691 patients into the cautionary group, and 812 patients into the unsuitable group. The 5-year rate of ipsilateral breast recurrence for suitable, cautionary, and unsuitable groups were 1.5%, 4.4%, and 8.8%, respectively (p = 0.0003). Whereas the regional node relapse showed no difference, the rate of distant metastases was significantly different in the unsuitable group compared with the suitable and cautionary groups, having a significant impact on survival. CONCLUSION In the context of patients treated with ELIOT, the ASTRO guidelines identify well the groups for whom APBI might be considered as an effective alternative to whole breast radiotherapy and also identify groups for whom APBI is not indicated.

PRELIMINARY RESULTS OF ELECTRON INTRAOPERATIVE THERAPY BOOST AND HYPOFRACTIONATED EXTERNAL BEAM RADIOTHERAPY AFTER BREAST-CONSERVING SURGERY IN PREMENOPAUSAL WOMEN

PURPOSE To report the acute and preliminary data on late toxicity of a pilot study of boost with electron intraoperative therapy followed by hypofractionated external beam radiotherapy (HEBRT) of the whole breast. METHODS AND MATERIALS Between June 2004 and March 2007, 211 women with a diagnosis of early-stage breast cancer were treated with breast-conserving surgery. During surgery, an electron intraoperative therapy boost of 12 Gy was administered to the tumor bed. Adjuvant local treatment was completed with HEBRT, consisting of a course of 13 daily fractions of 2.85 Gy to the whole breast to a total dose of 37.05 Gy. Acute toxicity of the breast was evaluated at the end of HEBRT and at 1 month of follow-up. Late toxicity was recorded at 6 and 12 months of follow-up. RESULTS We report the data from 204 patients. The maximal acute skin toxicity was observed at the end of HEBRT (182 patients evaluable) with 7 (3.8%) Grade 3, 52 (28.6%) Grade 2, 123 (67.6%) Grade 1, and no Grade 0 or Grade 4 cases. A total of 108 patients were evaluated for late toxicity. The recorded late skin toxicity was Grade 4 in 1 patient (0.9%), Grade 3 in 1 patient, and Grade 2 or less in 106 patients (98.2%). CONCLUSIONS The results of this study have shown that electron intraoperative therapy followed by HEBRT allows for the delivery of a high dose to the tumor bed and an adequate dose to the whole breast. This treatment is feasible, compliance is high, and the rate of acute toxicity and the preliminary data on chronic toxicity seem acceptable.

Three-dimensional conformal or stereotactic reirradiation of recurrent, metastatic or new primary tumors. Analysis of 108 patients.

Purpose:To analyze the outcome of reirradiation of recurrent/metastatic or new primary tumors with three-dimensional conformal (3D-CRT) or stereotactic (SRT) techniques.Patients and Methods:108 patients reirradiated between 01/2002 and 01/2005 at the European Institute of Oncology, Milan, Italy, were analyzed. Primary diagnosis included breast, lung, head/neck, urologic tumors, and other primaries. Curative and palliative intent were applied to 27 (25%) and 81 patients (75%), respectively. 3D-CRT and SRT were employed in 57 (53%) and 48 patients (44%), respectively, up to a mean dose of 23 Gy.Results:Median follow-up was 7 months (range, 1–50 months). Response, stabilization, and progression were observed in 33%, 36%, and 17% of patients, respectively (15 patients were not evaluable). No severe toxicity was reported. Median overall survival amounted to 32.6 months and was longer in patients treated with curative intent.Conclusion:A small portion of patients can be cured with a second course of radiotherapy, and in many cases, palliation can be obtained. Low toxicity of reirradiation with use of modern techniques should allow for the delivery of higher doses and, in consequence, lead to an improvement in reirradiation outcome.Ziel:Analyse der Therapieergebnisse nach Rebestrahlung von Rezidivtumoren, Metastasen oder Zweittumoren mit dreidimensionaler Konformationsstrahlentherapie (3D-CRT) oder stereotaktischer Radiotherapie (SRT).Patienten und Methodik:108 zwischen 01/2002 und 01/2005 am European Institute of Oncology, Mailand, Italien, rebestrahlte Patienten wurden analysiert. Bei Erstdiagnose lagen Tumoren der Mamma, der Lunge, des HNO-Bereichs sowie urologische und andere Tumoren vor. 27 Patienten (25%) wurden mit kurativer Zielsetzung und 81 (75%) in palliativer Absicht mit einer mittleren Gesamtdosis von 23 Gy bestrahlt.Ergebnisse:Die mediane Nachbeobachtungszeit betrug 7 Monate (1–50 Monate). Ansprechen, Stabilisierung und Progression wurden bei 33%, 36% und 17% der Patienten beobachtet. 15 Patienten konnten nicht ausgewertet werden. Schwerwiegende Toxizität wurde nicht beobachtet. Das mediane Gesamtüberleben lag bei 32,6 Monaten und war bei Patienten, die in kurativer Absicht behandelt wurden, länger.Schlussfolgerung:Ein kleiner Teil der Patienten kann durch eine Rebestrahlung in Remission gebracht werden, in vielen Fällen lässt sich eine Palliation erreichen. Die gute Verträglichkeit der Rebestrahlung bei Verwendung moderner Techniken ermöglicht zukünftig die Applikation einer höheren Dosis und damit evtl. auch eine weitere Verbesserung der Ergebnisse.

Three-Dimensional Conformal or Stereotactic Reirradiation of Recurrent, Metastatic or New Primary Tumors

Purpose:To analyze the outcome of reirradiation of recurrent/metastatic or new primary tumors with three-dimensional conformal (3D-CRT) or stereotactic (SRT) techniques.Patients and Methods:108 patients reirradiated between 01/2002 and 01/2005 at the European Institute of Oncology, Milan, Italy, were analyzed. Primary diagnosis included breast, lung, head/neck, urologic tumors, and other primaries. Curative and palliative intent were applied to 27 (25%) and 81 patients (75%), respectively. 3D-CRT and SRT were employed in 57 (53%) and 48 patients (44%), respectively, up to a mean dose of 23 Gy.Results:Median follow-up was 7 months (range, 1–50 months). Response, stabilization, and progression were observed in 33%, 36%, and 17% of patients, respectively (15 patients were not evaluable). No severe toxicity was reported. Median overall survival amounted to 32.6 months and was longer in patients treated with curative intent.Conclusion:A small portion of patients can be cured with a second course of radiotherapy, and in many cases, palliation can be obtained. Low toxicity of reirradiation with use of modern techniques should allow for the delivery of higher doses and, in consequence, lead to an improvement in reirradiation outcome.Ziel:Analyse der Therapieergebnisse nach Rebestrahlung von Rezidivtumoren, Metastasen oder Zweittumoren mit dreidimensionaler Konformationsstrahlentherapie (3D-CRT) oder stereotaktischer Radiotherapie (SRT).Patienten und Methodik:108 zwischen 01/2002 und 01/2005 am European Institute of Oncology, Mailand, Italien, rebestrahlte Patienten wurden analysiert. Bei Erstdiagnose lagen Tumoren der Mamma, der Lunge, des HNO-Bereichs sowie urologische und andere Tumoren vor. 27 Patienten (25%) wurden mit kurativer Zielsetzung und 81 (75%) in palliativer Absicht mit einer mittleren Gesamtdosis von 23 Gy bestrahlt.Ergebnisse:Die mediane Nachbeobachtungszeit betrug 7 Monate (1–50 Monate). Ansprechen, Stabilisierung und Progression wurden bei 33%, 36% und 17% der Patienten beobachtet. 15 Patienten konnten nicht ausgewertet werden. Schwerwiegende Toxizität wurde nicht beobachtet. Das mediane Gesamtüberleben lag bei 32,6 Monaten und war bei Patienten, die in kurativer Absicht behandelt wurden, länger.Schlussfolgerung:Ein kleiner Teil der Patienten kann durch eine Rebestrahlung in Remission gebracht werden, in vielen Fällen lässt sich eine Palliation erreichen. Die gute Verträglichkeit der Rebestrahlung bei Verwendung moderner Techniken ermöglicht zukünftig die Applikation einer höheren Dosis und damit evtl. auch eine weitere Verbesserung der Ergebnisse.

Tailoring treatment for ductal intraepithelial neoplasia of the breast according to Ki-67 and molecular phenotype

Background:The post-surgical management of ductal intraepithelial neoplasia (DIN) of the breast is still a dilemma. Ki-67 labelling index (LI) has been proposed as an independent predictive and prognostic factor in early breast cancer.Methods:The prognostic and predictive roles of Ki-67 LI were evaluated with a multivariable Cox regression model in a cohort of 1171 consecutive patients operated for DIN in a single institution from 1997 to 2007.Results:Radiotherapy (RT) was protective in subjects with DIN with Ki-67 LI ≥14%, whereas no evidence of benefit was seen for Ki-67 LI <14%, irrespective of nuclear grade and presence of necrosis. Notably, the higher the Ki-67 LI, the stronger the effect of RT (P-interaction <0.01). Hormonal therapy (HT) was effective in both Luminal A (adjusted hazard ratio (HR)=0.56 (95% CI, 0.33–0.97)) and Luminal B/Her2neg DIN (HR 0.51 (95% CI, 0.27–0.95)).Conclusion:Our data suggest that Ki-67 LI may be a useful prognostic and predictive adjunct in DIN patients. The Ki-67 LI of 14% could be a potential cutoff for better categorising this population of women at increased risk for breast cancer and in which adjuvant treatment (RT, HT) should be differently addressed, independent of histological grade and presence of necrosis.

A double-blind, randomised, vehicle-controlled clinical study to evaluate the efficacy of MAS065D in limiting the effects of radiation on the skin: interim analysis

Our aim was to assess the efficacy of MAS065D, a non-steroidal water-in-oil cream, in preventing and limiting skin reactions caused by radiation therapy (RT). 40 women treated with conservative breast cancer surgery followed by radiotherapy, were randomised to receive MAS065D (22 pts) or vehicle (18 pts). Radiotherapy was delivered in 20 fractions: 2.25 Gy to the whole breast plus a concomitant boost of 0.25 Gy to the tumour bed up to a total dose of 50 Gy. Evaluations of skin toxicity, erythema, and subjective symptoms were carried out weekly and 3 weeks after treatment completion. A statistically significant difference between vehicle and MAS065D groups was recorded regarding the maximum severity of skin toxicity (p < 0.0001), burning within the radiation field (p = 0.039) and desquamation (p = 0.02), in favour of the latter. We conclude that MAS065D may be considered a safe and effective treatment in the prevention and minimization of skin reactions and associated symptoms.

Capecitabine Initially Concomitant to Radiotherapy Then Perioperatively Administered in Locally Advanced Rectal Cancer

PURPOSE To evaluate the impact of neoadjuvant capecitabine, concomitant to radiotherapy, followed by capecitabine monotherapy, in operable locally advanced rectal cancer (LARC) by measuring pathologic response and conservative surgery rate, toxicity profile, and disease-free survival (DFS). METHODS AND MATERIALS From October 2002 to July 2006, a total of 51 patients affected by LARC (T3-T4 or any node positive tumor), received capecitabine (825 mg/m(2), orally, twice daily continuously) concomitant to radiotherapy on the pelvis (50.4 Gy/ 28 fractions), followed by two cycles of capecitabine (1,250 mg/m(2), orally, twice daily, 14 days on 7 days off) up until 2 weeks before surgery. Tailored adjuvant systemic treatment was discussed according to pathologic stage. RESULTS Of 51 patients, (median age 61 years, range 38-82 years; 19 women and 32 men; ECOG performance status 0/1/2: 46/4/1), 50 were evaluable for response: 18% complete pathologic remission; 12% T-downstaging, and 30% N-downstaging. One patient died before surgery from mesenteric stroke. Grade 3 acute toxicities were 2% diarrhea, 8% dermatitis, 2% liver function test elevation, and 2% hand-foot syndrome. Sphincter preservation rates for tumors < or =6 cm from the anal verge were 62% and 80% for the whole population. Median follow up was 43.0 months (range 0.8-68.6 months). Five-years DFS was 85.4% (95% CI = 75.3-95.4%). CONCLUSIONS Based on our study results, we conclude that this regimen is well tolerated and active and compares favorably with existing capecitabine-based approaches.

Long-term side effects and cosmetic outcome in a pool of breast cancer patients treated with intraoperative radiotherapy with electrons as sole treatment

AIMS To evaluate late toxicity and cosmetic outcome after intraoperative radiotherapy using electrons (ELIOT) as sole treatment modality in early breast cancer patients. METHODS A total of 119 patients selected randomly among 1200 cases was analyzed. Late toxicities were documented using the LENT-SOMA scoring system, cosmesis was evaluated with the Harvard scale, and a numeric rating scale was used to assess symptoms. RESULTS After a median follow-up of 71 months, grade II fibrosis was observed in 38 patients (31.9%) and grade III fibrosis in 7 patients (5.9%). Postoperative complications (12.6%) did not correlate with late toxicity. Physicians and patients scored cosmesis as excellent or good in 84% and 77.3% of the cases, respectively. Patient satisfaction was higher than 90%. CONCLUSIONS In the study, ELIOT gives low and acceptable long-term toxicity. A longer follow-up and a larger number of patients are needed to confirm these promising results.