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Introduction Two randomized intraoperative radiation therapy trials for early-stage breast cancer were recently published. The ELIOT Trial used electrons (IOERT), and the TARGIT-A Trial Update used 50-kV X-rays (IORT). These studies were compared for similarities and differences. The results were analyzed and used to determine which patients might be suitable for single-dose treatment. Method The primary sources of data were the ELIOT Trial and TARGIT-A Trial, as well as a comprehensive analysis of the peer-reviewed literature of accelerated partial breast irradiation (APBI) using 50-kV X-rays or electrons. Studies published or presented prior to March 2014 were analyzed for efficacy, patient restrictions, complications, and outcome. Results With a median follow-up of 5.8 years, the 5-year recurrence rates for ELIOT versus external beam radiation therapy (EBRT) patients were 4.4 % and 0.4 %, respectively, p = .0001. A low-risk ELIOT group was identified with a 5-year recurrence rate of 1.5 %. With a median follow-up of 29 months, the 5-year recurrence rates for the TARGIT-A versus EBRT patients were 3.3 % and 1.3 %, respectively, p = .042. Conclusion With 5.8 years of median follow-up, IOERT appears to have a subset of low-risk women for whom IOERT is acceptable. With 29 months of median follow-up the results of IORT with 50-kV devices are promising, but longer follow-up data are required. At the current time, single-fraction IOERT or IORT patients should be treated under strict institutional protocols.

Background: Women with early stage disease not only have a better prognosis, but also have the opportunity to preserve their breasts. Despite the positive evidence and outcomes for breast-conserving therapy (BCT), many women are unable or unwilling to undergo 5–7 weeks of external-beam radiotherapy (EBRT). We report the results of a single-institution phase II trial of accelerated partial breast irradiation (APBI) using a single dose of intraoperative electron radiotherapy (IOERT) in patients with low risk early stage breast cancer. Methods and materials: From July 2006 to December 2009, 226 patients suitable for BCT were enrolled in a phase II trial with IOERT as radical treatment immediately after surgical resection. All patients had biopsy proven cancer. After the surgeon temporarily re-approximated the excision cavity, a dose of 21 Gy using IOERT was delivered to the tumor bed with a margin of 2 cm laterally. Results: No acute reactions were reported after irradiation. Three patients experienced a transient edema. In 7 others a haematoma was observed. No cases of liponecrosis were observed. With a mean follow-up of 49 months (range 31–66 months), only one case of local recurrence has been reported. The observed toxicity was considered acceptable. As to cosmetic results, at 6 months after the end of IORT, 71/226 patients (31.4.%) had a score of 2 for symmetry and contour (asymmetry exhibited by 1/3 or less of volume breast), while 19/226 (8.4%) had a score 3 (asymmetry greater than 1/3 of breast volume). These findings remained unchanged at the following examinations. No breast oedema, discoloration at site or scar prominence were observed. Discussion: IOERT has significant advantages compared to other post-operative APBI approaches. The surgical re-approximation of the tumor bed, combined with the high quality of electron beam radiation, generates substantially more uniform dose distributions. IOERT offers the advantage of an excellent delineation of the tumor bed under visual control and high sparing of normal tissue, including the skin. IOERT delivers a very high biologically dose at the time of the surgery, when residual tumor cells are more rapidly proliferating. IOERT is insensitive to chemotherapy sequencing since all of the radiation is given during the surgery. IOERT offers low-risk women the possibility of a one-day procedure to treat their cancer and preserve their breast. The results of our study are very encouraging compared with other series with IOERT or APBI. The absolute recurrence rate of 0.4% and the recurrence rate per year of 0.2% of the present study are lower compared to the ones from the largest series with IOERT ever published (3.6% and 1.2%, respectively) (1). Conclusion: APBI using a single dose of IOERT can be delivered safely in women with early, low risk breast cancer. A longer follow-up is needed to ascertain its efficacy compared to that of the current standard treatment of whole breast irradiation. References 1. Veronesi U, Orecchia R, Luini A, et al. Intraoperative radiotherapy during breast conserving surgery: a study on 1,822 cases treated with electrons. Breast Cancer Res Treat 2010; 124:141–151. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-16-08.

Background We report the results of a single-institution, phase II trial of accelerated partial breast irradiation (APBI) using a single dose of intraoperative electron radiation therapy (IOERT) in patients with low-risk early stage breast cancer. Methods and Materials A cohort of 226 patients with low-risk, early stage breast cancer were treated with local excision and axillary management (sentinel node biopsy with or without axillary node dissection). After the surgeon temporarily reapproximated the excision cavity, a dose of 21 Gy using IOERT was delivered to the tumor bed, with a margin of 2 cm laterally. Results With a mean follow-up of 46 months (range, 28-63 months), only 1 case of local recurrence was reported. The observed toxicity was considered acceptable. Conclusions APBI using a single dose of IOERT can be delivered safely in women with early, low-risk breast cancer in carefully selected patients. A longer follow-up is needed to ascertain its efficacy compared to that of the current standard treatment of whole-breast irradiation.

Summary of phase II–III trials in LAPC (*CT combined with HT). GEM: Gemcitabine, CDDP: cisplatin, 5FU: 5-fluoracil, Oxa: Oxaliplatin. Tabelle 5. Zusammenfassung der Phase-II/III-Studien bei LAPC (*CT Kombiniert mit HT). GEM: Gemcitabin, CDDP: Cisplatin, 5FU: 5-Fluoracil, Oxa: Oxaliplatin. Study Patients (n)CT RT 1-year OSMedian OS (months) Moertel, 1981 86 5FU 60 Gy/30 F 46% 11.4GITSG, 1988 22 5FU 54 Gy/27 F 41% 9.7Ishii, 1997 20 5FU 50.4 Gy/28 F 42% 10.3Kornek, 2000 38 5FU - CDDP 55 Gy/28 F 53% 14Crane, 2001 51 GEM 30 Gy/10 F 10.3Louvet, 2002 30 GEMOX 47% 11.5El - Rayes, 2003 16 GEM - CDDP - 5FU 35% 10.3Cohen, 2005 55 5FU - Mitomycin C 59.4 Gy/33 F 8.4Haddock, 2007 47 GEM - CDDP 50.4 Gy/25 F 40% 10.2Huguet, 2007 128 GEM/GEMOX FOLFUGEM 65 Gy/38 F 47% 65%11.7 15Chauffert, 2008 119 GEM 5FU - CDDP 60 Gy/30 F 13 8.6Loehrer, 2008 74 GEM 1000 mg/mqGEM 600 mg/mq50.4 Gy/25 F 9.2 11Issels*, 2008 22 GEM - CDDP 16.9Ishikawa*, 2008 7 GEM 10.9Wilkowski, 2009 95 5FU GEM - CDDP GEM - CDDP 50 Gy/25 F 50 Gy/25 F 50 Gy/25 F 9.6 9.3 7.3Goldstein, 2009 48 GEM - OXA - 5FU 54 Gy/27 F 15.4Viret, 2009 51 DOCETAXEL - CDDP 54 Gy/27 F 9.6Colucci, 2010 199 GEM 8.3

Delineation of clinical target volume (CTV) is still controversial in glioblastomas. In order to assess the differences in volume and shape of the radiotherapy target, the use of pre-operative vs post-operative/pre-radiotherapy T(1) and T(2) weighted MRI was compared.4 CTVs were delineated in 24 patients pre-operatively and post-operatively using T(1) contrast-enhanced (T1(PRE)CTV and T1(POST)CTV) and T(2) weighted images (T2(PRE)CTV and T2(POST)CTV). Pre-operative MRI examinations were performed the day before surgery, whereas post-operative examinations were acquired 1 month after surgery and before chemoradiation. A concordance index (CI) was defined as the ratio between the overlapping and composite volumes.The volumes of T1(PRE)CTV and T1(POST)CTV were not statistically different (248 ± 88 vs 254 ± 101), although volume differences100 cm(3) were observed in 6 out of 24 patients. A marked increase due to tumour progression was shown in three patients. Three patients showed a decrease because of a reduced mass effect. A significant reduction occurred between pre-operative and post-operative T(2) volumes (139 ± 68 vs 78 ± 59). Lack of concordance was observed between T1(PRE)CTV and T1(POST)CTV (CI = 0.67 ± 0.09), T2(PRE)CTV and T2(POST)CTV (CI = 0.39 ± 0.20) and comparing the portion of the T1(PRE)CTV and T1(POST)CTV not covered by that defined on T2(PRE)CTV images (CI = 0.45 ± 0.16 and 0.44 ± 0.17, respectively).Using T(2) MRI, huge variations can be observed in peritumoural oedema, which are probably due to steroid treatment. Using T(1) MRI, brain shifts after surgery and possible progressive enhancing lesions produce substantial differences in CTVs. Our data support the use of post-operative/pre-radiotherapy T(1) weighted MRI for planning purposes.

Aims and background Hyperthermia, the heating of tumors to 41.5–43 °C, could be today considered the fourth pillar of the treatment of cancer. Employed for 20 years in Europe, the USA and Asia, hyperthermia, used in addition to radiotherapy, chemotherapy and surgery, increases both local control and overall survival, restores the chance of the surgery for inoperable tumors and allows a new low-dosage treatment of relapsed cancers previously treated with high radiotherapy dosage without increasing toxicity. Methods Hyperthermia can be either superficial, produced by a microwave generator, or regional, produced by a radiofrequency applicator with multiple antennas, which emanate a deep focalized or interstitial heating. Results The results are confirmed by phase III randomized trials, with level 1 evidence. A review of the international literature on hyperthermia, the experience of the University Hospital of Verona Radiotherapy Department (Italy) and a summary of the Symposium regarding the Evolution of Clinical Hyperthermia plus Radiotherapy during the Twentieth Congress of the French Society of Radiation Oncology (SFRO) are presented. Conclusions Hyperthermia is an important treatment modality in cancer treatment and its results are strongly supported by criteria of evidence-based medicine. Fifteen years of experience of the Radiation Oncology Department in Verona confirms the positive results obtained with international prospective trials, with level 1 evidence. Hyperthermia appears to be the fourth pillar beside surgery, radiotherapy and chemotherapy. Free full text available at www.tumorionline.it

To evaluate the safety of delivering pre-operative regional hyperthermia (HT) plus an intensified chemo-radiotherapy (CRT) regimen in patients suffering from locally advanced rectal cancer.Between June 2000 and April 2006, 76 patients with locally advanced (cT3-4 N0/+) rectal adenocarcinoma were treated with HT plus CRT. HT was given once a week, to a total of five treatments, 1 to 4 h after radiotherapy (50 Gy with 2-Gy fractions for 5 weeks, plus a 10-Gy boost on the tumour bed, with the same fractionation schedule). Chemotherapy consisted in 5FU 200 mg/m(2) continuous infusion throughout the 6 weeks of irradiation and OXA 45 mg/m(2) in a weekly bolus. Surgery followed 4 to 6 weeks after the completion of HT plus CRT.HT plus CRT was generally well tolerated. At pathologic examination, there was a pathologic complete response (pCR) (ypT0 ypN0) in 18 out of 76 patients (23.6%), a partial response (PR) in 34/76 ones (44.7%) and a stable disease (SD) in 20/76 (26.3%) ones; 4/76 patients (5.2%) had a progression disease (PD) (distant metastases) at the time of surgery. Good predictors of a longer disease-free survival (DFS) were in order ypN status (log-rank test: p = 0.0008), ypT status (p = 0.002) and pCR (p = 0.03).Preoperative CRT combined with regional HT yielded acceptable toxicity. The rate of pCR was encouraging, although further studies are needed to prove the long-term efficacy of adding HT to CRT.

Purpose We performed a new phase II trial enrolling patients with newly diagnosed high-grade glioma (HGG) to test the efficacy of a weekly alternating temozolomide (TMZ) schedule after surgery and concomitant chemoradiotherapy. Methods From January 2005 to January 2007, 34 patients (21 men, 13 women; age range 30–70, mean age 53) were enrolled. There were 32 glioblastoma multiforme and two anaplastic astrocytoma. Each patient after surgery received standard concurrent chemoradiotherapy. After a 4-week break, patients were then to receive 12 cycles of 1-week-on/1-week-off TMZ, with 75 mg/m2 for the first cycle, 100 mg/m2 for the second, 125 mg/m2 for the third, and 150 mg/m2 from the fourth to the 12th. Hematological toxicity was monitored every week during concomitant chemoradiotherapy and then every 4 weeks. Results After 12 months from the end of radiotherapy, the overall survival (OS) rate was 59% (20/38), distributed as follows: 60% (18/30) for recursive partitioning analysis (RPA) class 4 patients and 33% (1/3) for RPA class 6 patients; the only RPA class 1 patient was alive and disease free at the time of writing. Median OS was 13 months [95% confidence interval (CI) 11.02–14.98 months]. Hematological toxicity was seen in six patients (18%): grade 1 neutropenia in four, grade 2 thrombocytopenia in one, and grade 4 thrombocytopenia plus grade 1 neutropenia in one. There was one case of opportunistic infection (Pneumocystis carinii pneumonitis). Conclusion The toxicity of the TMZ dose-dense regimen was very low. Results seem to be encouraging for RPA lower classes (patients with good prognostic factors).

Purpose: Hyperthermia has been used in several trials to treat pelvic cancers without excessive toxicity and with positive results. The aim of this study was to evaluate feasibility and results in terms of biochemical recurrence-free, disease-free survival, overall survival, and treatment toxicity profile of hyperthermia combined with radiotherapy in locally advanced high risk prostate cancer. Patients and methods: From November 1998 to December 2004, 144 patients with locally advanced prostate cancer (LAPC) were enrolled in a phase II study. They were treated using conformal radiotherapy (CRT) plus local hyperthermia (LHT) and androgen suppression therapy (AST). Treatment modalities consisted of: 1) CRT with a mean dose of 74 Gy (2 Gy/ fraction/5 fractions per week); 2) LHT: one session per week during the first, second, third, and fourth week of the radiotherapy course; 3) AST was administered as neo-adjuvant and adjuvant therapy in more than 60% of patients. Results: The median follow-up time was 51.7 months. Four patients were lost at follow-up. Of 140 evaluated patients, four died because of intercurrent diseases and 12 because of progression of disease. Patients were evaluated in terms of five-year overall survival (87%), and five-year biochemical progression-free survival (49%). No significant side effects, except symptoms related to AST have been reported. No late grade 3 toxicity occurred. Conclusions: In advanced high risk prostatic cancer, hyperthermia is feasible and well tolerated. It may be useful to enhance the radiotherapy efficacy at intermediate dose in order to avoid higher doses of irradiation which increases acute and late sequelae. The advantage of LHT combined with CRT should be confirmed by a randomized phase III trial, comparing irradiation plus AST with or without hyperthermia.

In patients with locoregional recurrences of breast cancer not suitable for resection, subsequent local control is difficult to maintain in previously irradiated areas when reirradiation alone or reirradiation with chemotherapy is used. Due to the limited number of treatment options there is a high risk of subsequent failure and uncontrollable local disease. In this group of patients, local hyperthermia combined with radiotherapy increases the clinical response and local control, adding limited acute and late toxicity, as has been shown in randomized trials. Hyperthermia is an artificial elevation of tissue temperature (range 40-44°C for 30-60 min). If hyperthermia is applied shortly before or after radiation, the effect of radiation is enhanced by influencing intratumoral hypoxia and by inhibiting sublethal damage repair in the tumor. Moreover, hyperthermia combined with radiation reduces the total dose of radiation needed compared to radiation alone, of which a higher dose is needed to obtain the same effect. Few data are available on the combination of radiotherapy and hyperthermia with chemotherapy, although the results of trimodality treatment consisting of reirradiation and hyperthermia together with liposomal doxorubicin are promising. Therefore, this literature review was performed to provide more comprehensive data on the mechanism and use of hyperthermia in locoregional recurrence of breast cancer.

Purpose: To compare the epidemiologic, morphologic, and clinical characteristics of 92 children/adolescents (Group A) and 362 adults (Group B) with cerebral arteriovenous malformations (cAVMs) considered suitable for radiosurgery; to correlate radiosurgery-related permanent complication and post-radiosurgery bleeding rates in the 75 children/adolescents and 297 adults available for follow-up. Methods and Materials: Radiosurgery was performed with a model C 201-source Co 60 Leksell Gamma Unit (Elekta Instruments, Stockholm, Sweden). Fisher exact two-tailed, Wilcoxon rank–sum, and two-sample binomial exact tests were used for statistical analysis. Results: There were significant differences between the two populations in sex ( p = 0.015), clinical presentation ( p = 0.001), and location ( p = 0.008). The permanent complication rate was lower in younger (1.3%) than in older patients (5.4%), although the difference was not significant ( p = 0.213). The postradiosurgery bleeding rate was lower in Group A (1.3%) than in Group B (2.7%) ( p = 0.694), with global actuarial bleeding rates of 0.56% per year and 1.15% per year, respectively. Conclusions: The different characteristics of child/adolescent and adult cAVMs suggest that they should be considered two distinct vascular disorders. The similar rates of radiosurgery-related complications and latency period bleeding in the two populations show that gamma knife radiosurgery does not expose young patients to a higher risk of sequelae than that for older patients.

Background: Intraoperative radiotherapy during breast-conserving surgery is being studied as an alternative to 6 weeks of external beam radiotherapy (EBRT) for low-risk women; it can be delivered using electrons (intraoperative electron radiotherapy, IOERT) or 50-kV X-rays. Materials and Methods: We analyzed both single institutional and randomized studies involving single-fraction IOERT treatments. Rates for ipsilateral breast tumor recurrences, disease-specific survival, and overall survival were obtained. Results: IOERT had true 5-year recurrence rates of < 1.5% for ASTRO (American Society for Radiation Oncology) and ESTRO (European Society for Therapeutic Radiology and Oncology) suitable women, or for low-risk women as defined by the ELIOT trial. Women with ductal carcinoma in situ eligible for breast-conserving therapy, older women that currently receive no EBRT, and younger women with favorable biology are additional potential candidates. Conclusion: ASTRO suitable and ESTRO good women for accelerated partial breast irradiation are low-risk groups. Higher-risk women with favorable biology might also be suitable candidates for IOERT, providing the tumor biology can be determined prior to surgery. For intraoperative radiotherapy using 50-kV X-rays, follow-up was too short to assess the effectiveness of the treatment.

The Specific Absorption Rate (SAR) distribution pattern visualization by a matrix of E-field light-emitting sensors has demonstrated to be a useful tool to evaluate the characteristics of the applicators used in deep regional hyperthermia and to perform a quality assurance programme. A method to quantify the SAR from photographs of the sensor array--the so-called 'Power Stepping Technique'--has already been proposed. This paper presents a new approach to the quantitative determination of the SAR profiles in a liquid phantom exposed to electromagnetic fields from the Sigma-60 applicator (BSD-2000 system for deep regional hyperthermia). The method is based on the construction of a 'calibration curve' modelling the light-output of an E-field sensor as a function of the supplied voltage and on the use of a reference light source to 'normalize' the light-output readings from the photos of the sensor array, in order to minimize the errors introduced by the non-uniformity of the photographic process. Once the calibration curve is obtained, it is possible, with only one photo, to obtain the quantitative SAR distribution in the operating conditions. For this reason, this method is suitable for equipment characterization and also for the control of the repeatability of power deposition in time.

1059Background: Several phase III trials of breast IORT have recently been published with findings that have generated significant controversy and discussion. As different techniques were used in these trials in a broad range of patients, it is unclear if the results obtained were due to differences in technique, type of radiation or patient selection. The goal of the current study was to review findings from studies using only electron IORT in appropriately selected patients considered suitable for APBI. Methods: We performed a literature search addressing the use of electron IORT as the sole radiation treatment for early stage breast cancer. Publications that delivered IORT prior to tumor excision, and those that did not deliver the prescription dose as deeply as the chest wall, were excluded. The ASTRO and ESTRO Consensus guidelines were used to select patients from these studies based upon society derived criteria for the application of APBI. ESTRO Good category differs from ASTRO Suitable in that it ...

Meningiomas account for 16%-25% of all intracranial tumors, and quite often they rank amongst the most frequent neuro-oncological diagnostic subgroups in European or American registries (4, 5, 8, 54) As regards their natural history, (23, 29, 46, 55, 56, 59, 61) the few reported series of conservatively managed symptomatic meningiomas–bearing adequate FUhave documented a consistent progression in approximately one-third of patients, although in a wide spectrum of variability (TABLE 1).

Squamous-cell carcinoma of the head and neck includes a heterogeneous group of tumours of the upper air and food passages for which prognosis is difficult to assess. In fact, patients in comparable stages may have diverse clinical courses and responses to similar treatments. In order to better define the prognosis of each patient there is therefore a need to identify novel biological markers which reflect more accurately growth rate, progression and metastatic potential of each tumour. We assessed whether metastases correlate with micro-vessel counts (i.e. intratumoral vascularity) using the CD-31 monoclonal antibody (MAb) and p53 mutant protein expression, determined in the primary by immunocytochemical methods in 70 patients with locally advanced head and neck cancer. Patients were treated with concurrent chemo-radiotherapy; 50 of these presented loco-regional node metastasis at diagnosis whereas 3 cases, initially node-negative, developed distant metastasis during the period of observation. No feature was predictive for objective response to treatment. The overall mean and median blood vessel density at “hot spots” was 37.42 and 36, respectively, and 57% of the tumours expressed p53 mutant proteins. These 2 biological markers were significantly associated. Patients with metastases (loco-regional and distant) had a significantly higher mean blood-vessel density than those without tumour spread. Also, patients with p53-positive (+/ + +) tumours had a significantly higher incidence of metastasis than those with negative ones. Multivariate analysis showed that both vascularity and stage, but not p53 expression, are significant and independent predictors of metastasis in this series.

Purpose: Hyperthermia is now being widely used to treat clinical malignancies especially combined with radiotherapy and more rarely with chemotherapy. The combination of heat, radiation, and chemotherapy (trimodality) can lead to potent interaction. The present Phase I–II study was conducted to evaluate the feasibility and acute toxicity of a combination of cisplatin, hyperthermia, and irradiation in the treatment of superficial cervical nodal metastases from head and neck cancer. Methods and Materials: Eighteen patients with measurable neck metastases from previously untreated squamous cell head and neck tumors were entered into the trial. Therapy consisted of a conventional irradiation (total dose 70 Gy, 2 Gy five times a week) combined with a weekly administration of 20 mg/m 2 iv of cisplatin and a total of two sessions of local external microwave hyperthermia (desired temperature of 42.5°C for 30 min). Results: Feasibility of the treatment was demonstrated. Acute local toxicity was mild; no thermal blisters or ulcerations were reported and only two patients experienced local pain during hyperthermia. Cutaneous toxicity appeared greater than in our previous studies with irradiation plus hyperthermia and irradiation plus cisplatin. Systemic toxicity was moderate with major toxic effects observed in three patients (World Health Organization (WHO) grade 3 anaemia). Even though it was not an aim of the study to evaluate the nodal response, we observed a complete response rate of 72.2% (95% confidence interval 51–93.4%), 16.6% of partial response and 11.1% of no change. Conclusion: The study confirms the feasibility of the combination of cisplatin, heat, and radiation with an acceptable toxicity profile. The trimodal therapy deserves further evaluation as a way to enhance the efficacy of irradiation in the treatment of nodal metastases from head and neck tumors.

OBJECTIVE: To investigate the pattern of care and outcomes for newly diagnosed glioblastoma in Italy and compare our results with the previous Italian Patterns of Care study to determine whether significant changes occurred in clinical practice during the past 10 years. METHODS: Clinical, pathological, therapeutic, and survival data regarding 1059 patients treated in 18 radiotherapy centers between 2002 and 2007 were collected and retrospectively reviewed. RESULTS:Most patients underwent both computed tomography and magnetic resonance imaging either preoperatively (62.7%) or postoperatively (35.5%). Only 123 patients (11.6%) underwent a biopsy. Radiochemotherapy with temozolomide was the most frequent adjuvant treatment (70.7%). Most patients (88.2%) received 3-dimensional conformal radiotherapy. Median survival was 9.5 months. Two- and 5-year survival rates were 24.8% and 3.9%, respectively. Multivariate analysis showed the statistical significance of age, postoperative Karnofsky Performance Status scale score, surgical extent, use of 3-dimensional conformal radiotherapy, and use of chemotherapy. Use of a more aggressive approach was associated with longer survival in elderly patients. Comparing our results with those of the subgroup of patients included in our previous study who were treated between 1997 and 2001, relevant differences were found: more frequent use of magnetic resonance imaging, surgical removal more common than biopsy, and widespread use of 3-dimensional conformal radiotherapy + temozolomide. Furthermore, a significant improvement in terms of survival was noted (P < .001). CONCLUSION: Changes in the care of glioblastoma over the past few years are documented. Prognosis of glioblastoma patients has slightly but significantly improved with a small but noteworthy number of relatively long-term survivors.

We report a case of relapsed high-risk non-metastatic medulloblastoma in a 14-year-old boy, which was treated with intensity-modulated radiotherapy (IMRT) and temozolomide (TMZ). At the age of 11, the patient underwent an MRI-confirmed incomplete resection of a fourth-ventricle medulloblastoma, followed by conventional chemotherapy, craniospinal irradiation (55.8 Gy, 1.8 Gy/fraction) and then myeloablative chemotherapy followed by peripheral blood progenitor cell rescue. After 18 months of complete remission following the completion of chemotherapy, MRI showed a 2.5-cm mass in the olfactory notch. The patient underwent IMRT (45 Gy, 1.8 Gy/fraction) with concomitant administration of TMZ (180 mg/m2, 5 days every 21 days), which was well tolerated. After 5 cycles of TMZ, MRI showed complete remission with no evidence of the mass. TMZ was continued for another 5 cycles and then stopped. At 14 months from the completion of IMRT, a new MRI scan showed multiple nodular relapses around the fourth ventricle and the patient is currently treated with oral etoposide.

Undifferentiated small cell carcinoma of the bladder is a rare but aggressive subset of urinary tract neoplasms. Analogous to small-cell carcinoma of the lung, this tumor frequently exhibits neuroendocrine differentiation. We report the 92nd and 93rd case of small cell carcinoma of the bladder reported in the literature with characteristic cytologic, histologic, histochemical, and ultrastructural features. The patients were treated initially with chemotherapy, but after a brief clinical course died for progression of disease and for myocardial infarction, respectively. The pathologic and clinical features and therapeutic options of the cases described in the literature are reviewed.

To our knowledge, there are no published reports on the effectiveness of radiosurgery in the management of brain metastases from testicular nonseminomatous germ cell tumor. The authors evaluate the results of gamma knife (GK) treatment in three patients with these unusual intracranial lesions. Between April 1995 and July 2001, three patients with brain metastasis from testicular nonseminomatous germ cell tumor underwent adjuvant radiosurgery at our department. The primary tumor had been surgically removed in all cases. At diagnosis, one patient was stage IB and two were stage III poor risk. Chemotherapy and whole brain radiotherapy were administered before radiosurgery in all cases. Pre-GK radiotherapy was administered with a daily fraction dosage of 1.8-2.0 Gy. The indications for radiosurgery were tumor volume

Adjuvant pelvic radiotherapy (XRT) after radical surgery for uterine cancer may cause various (mainly gastrointestinal) side effects capable of affecting a patient's lifestyle. This prospective study used a diary card to evaluate toxicity and daily quality of life changes in uterine cancer patients given postoperative pelvic radiotherapy.The self-completed diary card listed 12 items concerning lifestyle changes and side effects. The patients were stratified by age (/=65 vs65 years).Twenty-five patients were evaluable, and a total of 848 days were assessed (82.6% of the 1027 days of XRT). The mean number of daily stools progressively increased during treatment (P0.01). No statistically significant differences were observed in terms of nausea or pain. There was a significant decrease in appetite (P0.01). Vaginal symptom scores did not significantly change during treatment, and no significant differences were found in terms of anxiety, daily activities, or compliance to therapy. The subjective perception of overall well-being and the quality of life score progressively and significantly decreased over time (P0.01). The younger patients had significantly more bowel movements, less appetite, more pain and vaginal burning, less vaginal bleeding, more anxiety, a greater reduction in daily activities and therapeutic compliance, a poorer subjective perception of overall well-being, and a lower quality of life score.The use of a diary card may be an adequate means of detecting the extent of treatment-related changes in the lifestyle of uterine cancer patients receiving postoperative radiotherapy.

PURPOSE: Adjuvant pelvic radiotherapy after radical surgery for rectal cancer may produce several side-effects (mainly gastrointestinal) capable of affecting patient lifestyle. This prospective study evaluated by means of a diary card the toxicity and daily changes in the quality of life of patients with rectal cancer treated with postoperative pelvic radiotherapy. METHODS: We used a diary card listing ten items about lifestyle changes and side-effects compiled by patients themselves. The patients were stratified by age (≤ 65 vs. > 65 years), the presence or not of a stoma, and the administration or not of concurrent chemotherapy. RESULTS: Twenty-seven patients were evaluable. The mean number of bowel movements increased across time, without statistically significant differences. Nausea and appetite did not significantly change during the treatment period. There was a statistically significant, progressive increase in the perception of pain (P < 0.03). Although not significantly, the anxiety scores were lower during radiotherapy than at baseline. Daily activities and compliance with therapy did not significantly change during the treatment. There was a significant worsening in overall well-being (P < 0.04) and quality of life evaluation (P < 0.03). The patients who received chemoradiotherapy experienced a worsened lifestyle and greater side-effects. Older patients experienced less pain but had statistically significant higher levels of anxiety. Patients with a stoma reported a better quality of life score than those without. CONCLUSIONS: The use of a diary card may be an adequate means of detecting the extent of treatment-related changes in the lifestyle of patients with rectal cancer treated by postoperative radiotherapy.

To evaluate the efficacy of Gamma Knife (GK) radiosurgery in terms of neurologic improvement and tumor growth control (TGC) in a large series of patients with cavernous sinus meningioma (CSM).One hundred thirty-eight patients with CSM (28 males, 110 females; mean age: 56.2 years) were treated with GK between February 1993 and February 2001. GK was used as a first-choice treatment in 68/138 patients and as postoperative adjuvant therapy in 70/138. In 32 patients, it was possible to compare the size of the planned treatment volume to tumor volume using the conformity index (CI); optimal CI values were taken to beor =1.5 (range: 0.94-2.24).A follow-up (FU) period of at least 12 months was available for 111 patients (median: 48.2 months, range: 12.1-84.5 months). Clinical conditions were improved or stable in 107/111 patients (96.5%). Neurologic recovery was observed in 76% of cases treated by GK alone and in 56.5% of adjuvant treatments (p0.03). Adequate TGC was documented in 108/111 tumors (97%), with shrinkage/disappearance in 70/111 (63%) and no variation in volume in 38/111 (34%); the overall actuarial progression-free survival rate at 5 years was 96%. Tumor size regression was observed in 79.5% of patients with FU30 months, compared with 47.5% of patients with FU30 months (p0.001). One hundred percent TGC was shown in treated patients with a CIor =1.5 (20/32), compared with 92% TGC in cases with a CI1.5 (p0.15, NS). Radiosurgical sequelae were transient in 4/111 cases (3.5%) and permanent in one case (1%).For the FU period of our series (median:4 years), GK radiosurgery seems to be both safe (permanent morbidity 1%) and effective (96% neurologic improvement/stability, 97% overall TGC, 96% actuarial TGC at 5 years) and might be considered as a first-choice treatment for selected patients with CSM.

The optimal treatment of ductal carcinoma in situ (DCIS) of the breast has not yet been established. The effectiveness of adjuvant postoperative radiotherapy after conservative surgery is debated. Few data are available in Italy on the combined treatment. A collaborative multi-institutional study on this issue in 10 radiation oncology departments of the north-east of Italy was conducted. One hundred and thirty nine women with DCIS of the breast were treated between 1980 and 1990. Age ranged between 28 and 88 years (median 50 years). Surgical procedures were: quadrantectomy in 108, lumpectomy in 22 and wide excision in 9 cases. The axilla was surgically staged in 97 cases: all the patients were node-negative. Radiation therapy was delivered with 60Co units (78%) or 6 MV linear accelerators (22%) for a median total dose to the entire breast of 50 Gy (mean 49.48 Gy; range 45–60 Gy). The tumour bed was boosted in 109 cases (78%) at a dose of 4–30 Gy (median 10 Gy) for a minimum tumour dose of 58 Gy. Median follow-up was 81 months. Thirteen local recurrences were recorded, 7 intraductal and 6 invasive. All recurrent patients had a salvage mastectomy and are alive and free of disease. Actuarial overall, cause-specific and recurrence-free survival at 10 years are of 93%, 100% and 86%, respectively. The results of this retrospective multicentric study substantiate the favourable data reported in the literature and confirm the efficacy of the breast-conserving treatment of DCIS employing conservative surgery and adjuvant radiation therapy.

143 Background: We report the results of a single-institution phase II trial of accelerated partial breast irradiation (APBI) using a single dose of intraoperative electron radiotherapy (IOERT) in patients with low-risk early-stage breast cancer. Methods: From July 2006 to December 2009, 226 patients suitable for BCT were enrolled in a phase II trial with IOERT as radical treatment immediately after surgical resection. All patients had biopsy-proven cancer. After the surgeon temporarily re-approximated the excision cavity, a dose of 21 Gy using IOERT was delivered to the tumor bed with a margin of 2 cm laterally. Results: No acute reactions were reported after irradiation. Three patients experienced a transient edema. In 7 others a haematoma was observed. No cases of liponecrosis were observed. With a mean follow-up of 49 months (range 31-66 months), only one case of local recurrence has been reported. The observed toxicity was considered acceptable. As to cosmetic results, at 6 months after the end of IORT, 71/226 patients (31.4.%) had a score of 2 for symmetry and contour (asymmetry exhibited by 1/3 or less of volume breast), while 19/226 (8.4%) had a score 3 (asymmetry greater than 1/3 of breast volume). These findings remained unchanged at the following examinations. No breast oedema, discoloration at site or scar prominence were observed. Conclusions: IOERT offers the advantage of an excellent delineation of the tumor bed under visual control and high sparing of normal tissue, including the skin. IOERT delivers a very high biologically dose at the time of the surgery, when residual tumor cells are more rapidly proliferating. IOERT is insensitive to chemotherapy sequencing since all of the radiation is given during the surgery. The absolute recurrence rate of 0.4% and the recurrence rate per year of 0.2% of the present study are very encouraging. APBI using a single dose of IOERT can be delivered safely in women with early, low-risk breast cancer. A longer follow-up is needed to ascertain its efficacy compared to that of the current standard treatment of whole breast irradiation.

Aims and backgroundPure testicular seminoma has historically been treated with post-orchidectomy radiation therapy with excellent results. Recently, several aspects of the treatment of stage I seminoma have been questioned. We assessed long-term results and toxicity of patients with pure testicular seminoma treated at the Department of Radiation Oncology of S. Chiara Hospital, Trento.MethodsFrom 1953 to 1987, 102 patients with stage I pure testicular seminoma were given megavoltage irradiation with curative intent. All patients had a minimum follow-up of 3 years (maximum 37 years, median 13 years). They received a mean para-aortic/pelvic dose of 33.07 Gy (range 23.70-45.20 Gy) with different doses and fields reflecting the change in techniques over a long period of time.ResultsThe cause-specific actuarial survival at 30 years was 99% and crude survival 67%. One patient had an out-field relapse (inguinal) after a few months and was cured with radiotherapy and chemotherapy. Another patient relapsed with widespared metastases and died after 1 year of progressive disease. Early toxycity was mild and the treatment was well tolerated. Late side effects were reported in 8/102 patients.ConclusionIn our series adjuvant radiation therapy resulted in cure rates corresponding to those reported in the literature. The 30-year actuarial survival of 99% was extremely good and the toxicity of the treatment was mild. Post-orchidectomy radiation to the para-aortic and ipsilateral pelvic nodes is a safe and effective method of preventing recurrences and is currently to be considered the treatment of choice in stage I testicular seminoma.

p53 expression detected by immunocytochemistry is emerging as a novel potentially useful prognostic indicator in breast carcinoma. However, additional research is warranted because a consensus has not yet been achieved on: i) methodology and quality control issues; ii) its association with other new biological prognostic indicators; iii) its prognostic value in multivariate analysis including conventional and new pathobiological features and; iv) its clinical usefulness either as a prognostic and predictive factor. This study was undertaken in a series of 165 early-stage breast cancer patients (median follow-up of 5 years) to compare the prognostic role of p53 expression with that of several other markers that have been found to be of value, using a multivariate statistical analysis. These factors are: tumour angiogenesis, epidermal growth factor receptor (EGFR), c-erbB-2 expression, cathepsin D, growth fraction by Ki-67 antibody, DNA ploidy and S-phase fraction. The main results observed were: i) 47 of 165 (28.5%) carcinomas had pAb 1801 staining and were considered as p53-positive; ii) p53 expression was weakly associated with S-phase fraction by flow cytometry (OR=1.86; p=0.085); iii) p53 expression was significantly associated with recurrence (p53 negative [-] versus weak positive [+] tumours: p=0.07 and odds ratio of 2.21; p53 negative [-] versus high positive [++] tumours: p=0.01 and odds ratio of 2.86) and death (p53-versus +: p=0.53 and odds ratio of 1.35; p53- versus ++: p=0.05 and odds ratio of 2.53); iv) the determination of p53 is able to identify a subset of high risk patients in c-erbB-2 negative tumours, this group being generally considered at good prognosis; v) In multivariate analysis on relapse-free survival including all the above markers only tumour angiogenesis, cathepsin D, EGFR and S-phase fraction and nodal status retained significance, and for overall survival only tumour angiogenesis was significant and independent. This new information on p53 expression could be useful to the clinician for a more rationale approach in defining prognosis of breast cancer patients. The prognostic value of p53 depends on which other markers are additionally analyzed and previous studies have not always assayed tumour angiogenesis, which is the most important factor in this series. p53 still need to be assessed as a potential predictor of response to chemo or radiotherapy, because of its role in monitoring DNA damage.

The type I growth factor receptor family has been found to play an important role in the control of normal growth and differentiation. Moreover, the epidermal growth factor receptor and the c- erb B-2 oncogene seem to be implicated in the pathogenesis and behaviour of several cancers, including breast cancer. c- erb B-3 is a new member of the type I receptor family for which there is currently little information available on its expression in neoplastic tissues, and on its possible prognostic significance. This study was undertaken to define the prognostic value of c- erb B-3 expression in a series of node-negative breast cancer (NNBC) patients when compared, by multivariate analysis, with expression of the c- erb B-2 protein and conventional clinicopathological features. c erb B-3 was recognised by the novel monoclonal antibody RTJ1, whereas c- erb B-2 was detected by the polyclonal antibody 21N, using immunocytochemical methods. We found that overexpression of c- erb B-3 occurs frequently in NNBC. Overall, 138 of 212 carcinomas (65%) had some degree of membrane RTJ1 staining, and 28 (13%) showed strong and generalised positivity (+++). Twenty-four per cent of carcinomas had membrane 21N staining, and 12% presented strong and generalised positivity (+++). c- erb B-3 protein expression was significantly associated only with that of c- erb B-2 ( P = 0.05), whereas 21N positivity was significantly associated with small tumour size ( P = 0.02) and ductal histotype ( P = 0.04). No significant correlation between expression of either receptor proteins or relapse-free survival was observed after a median follow-up of 63 months. Applying multivariate analysis, only tumour size approached significance. Our results indicate that analysis of expression of c- erb B-3 and c- erb B-2 alone do not seem to be useful in identifying patients with NNBC at different risk of relapse or death.

Several phase II studies have shown that concurrent chemotherapy and radiotherapy (RT) improves the response rates and locoregional control in patients with advanced, unresectable squamous-cell carcinoma of the head and neck (HN). However, it is still unclear which is the drug of choice to be given with RT. We therefore conducted a randomized comparison of cisplatin (CDDP)-RT versus carboplatin (CRP)-RT in such patients. The two platinum compounds were given at equitoxic doses. The primary objective of the study was to compare the side effects and the response rates of the two regimens. Radiotherapy was given at conventional dosages, 2 Gy for 5 days every week for a total dose of 64 Gy with CDDP 80 mg/m2 or CRP 375 mg/m2 for three cycles on days 1, 21 and 42. At present 53 patients are entered in the study: 27 in the CDDP arm and 26 in the CRP. The two arms were balanced for all the pre-treatment characteristics. Both the schedules were well tolerated. However, incidence of nausea and vomiting (p=0.0045); anemia (p=0.032) and peripheral neuropathy (p=0.032) was significantly greater with CDDP-RT as compared to CRP-RT. On the other hand, CRP-RT gives a significantly higher incidence of stomatitis (p=0.0067) and a marginally worse thrombocytopenia (p=0.09). The complete response (CR) rates were similar in the two arms (55.5% in the CDDP-RT versus 61.5% in that CRP-RT, respectively) as well as the overall response rates (92.5% versus 84.5%, respectively; p=0.36). The estimated 1 -and 2 year overall and disease-free survival rates were not significantly different in the two arms. In both the groups logistic-regression models showed that those patients with a CR (p=0.017); stage III (p=0.011); smaller primary (p=0.025) and limited node-involvement (p0.001) had a significant better survival. We conclude that concurrent chemo-radiotherapy is an effective and safe treatment for patients with locally advanced HN cancer. The combination CRP-RT possess a similar activity but a different, and perhaps a more favorable, spectrum of toxicity when compared to the CDDP-RT therapy. Survival results need to be assessed in a larger series and followed for a more prolonged time.

4548 Background: The achievement of pathological complete response (pCR) seems essential to improve survival in EC. In a phase I study (Pasini et al, Ann Oncol 2005) we demonstrated the feasibility of a novel protocol of neoadjuvant chemoradiation. Based on these promising results, we have performed a phase II study. The primary end point was the pathological response rate, the secondary end points were survival and toxicity. Methods: 74 pts with stage II-III EC (37 adenocarcinomas) were enrolled; median age was 59 yrs (42–73). Treatment consisted of D 35 mg/m2 and P 25 mg/m2 d 1,8,15,29,36,43,50,57 plus 5-FU 180 mg/m2 c.i. d 1–21 and 150 mg/m2 c.i. d 29–64; concurrent RT (50 Gy) started on d 29. Surgery was performed 6 to 8 weeks after completion of RT. Results: 65/74 pts (88%) completed the planned chemo-radiation, while 9 required dose modification of chemotherapy. Median follow-up of living pts was 40 mo (18–75). Pathological findings: pT0 pN0 (pCR): 35 (47%); pTrm pN0:11 (15%)[residual microfoci]; Others: 28 (38%). The overall median survival was 50 mo; median survival times of Others, pTrm, and pCR subsets were 17, 42 months and not reached, respectively (p [Table: see text] No significant financial relationships to disclose.

1572 Background: The efficacy of temozolomide (TMZ) is strictly related to the possibility to reach and maintain high and prolonged cellular drug concentrations in the target tissue. Evidence exists demonstrating that the achievement of this goal and the subsequent activity of TMZ are categorically schedule dependent. Aim of the present randomized phase II study is to verify whether a treatment schedule with TMZ appropriately modified induces better response rates along with a decrease of mielotoxicity as compared to the conventional one. Methods: Twenty patients (5 F/15 M), median age of 53 years (range 35–74), median Karnofsky PS 90 (range 70–100), with GBM in progression after surgery and adjuvant RT have been treated as follows: Schedule A - TMZ for 5 days in a 28-day cycle, at the dose of 150 mg/m2/d at the first cycle and of 200 mg/m2/d thereafter, up to a total of 8 cycles. Schedule B - TMZ for 7 days alternating with 7 days of rest up to a total of 12 cycles: the starting dose of TMZ at the first cycle was 50 mg/m2/d with progressive serial dose escalations of 25 mg/m2/d in the subsequent ones until the achievement of the dose of 150 mg/m2/d at the 5th cycle, and then keeping this regimen until the 12th cycle. Results: They are summarized in the table : Severe thrombocytopenia and stomatitis have been observed only in patients treated with Schedule A. Conclusions: These preliminary results, which deserve to be confirmed in a larger sample size, indicate that the treatment with TMZ on alternate week basis is strongly interesting and promising. In spite of the modality and the small number of patients included in this study, which doesn’t allow a direct comparison between two different treatments, it should be noted that schedule B achieved a 2-year OS and PFS rate of 40% and 20% respectively, compared to 10% and 0% of schedule A. [Table: see text] No significant financial relationships to disclose.

4059 Background: dose-dense therapy should allow more frequent delivery of moderate doses over a short period with greater efficacy and lower toxicity than standard doses every 3 weeks. This neodjuvant phase I protocol was based on weekly D and cisplatin (P), continuous infusion (c.i.) of 5-FU and concomitant RT. The doses of D and RT were progressively escalated. Aims were pathological response rate and toxicity. Methods: from Oct 99 to Oct 03, 41 non metastatic pts (31 adenocarcinomas) were enrolled; median age was 61 yrs (47–76). Step 1: D and P 20 mg/m2 d 1,8,15 plus 5-FU 150 mg/m2 c.i. d 1–21. After one week rest, the same cycle was repeated at days 28, 35, 42 concurrently with RT (40 Gy). Step 2: D and P 25 mg/m2; 5-FU 180 mg/m2 days 1–21. Step 3: 5-FU prolonged to four weeks during RT (150 mg/m2 days 28–56). Step 4: D and P 25 mg/m2 added at day 49. Step 5: RT increased to 50 Gy. Step 6: D 30 mg/m2. Step 7: D 35 and P 25 mg/m2 added at day 56 and 5-FU prolonged to 5 weeks. Surgery was performed 4 t...

Purpose To evaluate the outcome of pts treated with Breast-Conserving Surgery (BCS) and definitive irradiation (DR) for Ductal Carcinoma in situ of the breast (DCIS). Patients and methods 110 cases (104 evaluable) treated between 1980 and 1990 have been collected in 9 Italian Institutions. All the cases were treated with BCS (quadrantectomy 78, wide excision 8, tumorectomy 18) and DR (median breast total dose 50 Gy, median boost dose 10 Gy). Results Median follow up time was 62 months (range 21–151). There were 6 (5.7%) failures in the breast. Neither nodal recurrences or distant metastases were observed. All the 6 patients were salvaged with mastectomy. Five metachronous controlateral breast tumors (2 invasive) and 4 second tumors developed during follow-up. Five-year actuarial overall, cause specific and breast-recurrence free survival is 94.6%, 100% and 90% respectively. Conclusion This study confirm that RCS and DR is an effective alternative to mastectomy in the treatment of DCIS of the breast.

Twenty-eight patients affected with disseminated prostate cancer, which proved hormone resistant (after castration and oestrogen administration), have undergone combined treatment with Testosterone (for 13 days) and 32P (for the last 7 days of the Testosterone treatment). During the initial fase of the treatment (Testosterone only), 14 patients experienced pain exacerbation and/or fever and one experienced immediate improvement. The exacerbation quickly disappeared following 32P administration, and 26 of the patients had distinct improvement at some time during or after treatment, with a mean remission duration of 3 months and mean survival rate of 7 months. No lytic or soft part deposit showed improvement; improvement was noticeable only in the mixed type or osteo-sclerotic metastases. This observation suggests that the androgen stimulates uptake of the isotope not inside the tumor cells but in the bone matrix around the tumoral deposit. The patient who showed very early improvement had a subsequent relapse on oestrogens, but later responded to the androgen alone.

Background Two randomized intraoperative radiation therapy trials for early-stage breast cancer were recently published. The ELIOT Trial used electrons (IOERT), and the TARGIT-A Trial Update used 50-kV X-rays (IORT). These studies were compared for similarities and differences. The results were analyzed and used to determine which patients might be suitable for single-dose treatment. Methods The primary sources of data were the ELIOT Trial and TARGIT-A Trial, as well as a comprehensive analysis of the peer-reviewed literature of accelerated partial breast irradiation (APBI) using 50-kV X-rays or electrons. Studies published or presented prior to March 2014 were analyzed for efficacy, patient restrictions, complications, and outcome. Results With a median follow-up of 5.8 years, the 5-year recurrence rates for ELIOT versus EBRT patients were 4.4 and 0.4 %, respectively, p = 0.0001. A low-risk ELIOT group was identified with a 5-year recurrence rate of 1.5 %. With a median follow-up of 29 months, the 5-year recurrence rates for the TARGIT-A versus EBRT patients were 3.3 and 1.3 %, respectively, p = 0.042. Conclusions With 5.8 years of median follow-up, IOERT appears to have a subset of low risk women for whom IOERT is acceptable. With 29 months of median follow-up the results of IORT with 50-kV devices are promising, but longer follow-up data are required. At the current time, single-fraction IOERT or IORT patients should be treated under strict institutional protocols.

PURPOSE To determine the absolute and relative value of microvessel density (MVD), p53 and c-erbB-2 protein expression, peritumoral lymphatic vessel invasion (PLVI), and conventional prognosticators in predicting relapse-free (RFS) and overall survival (OS) rates in patients with node-negative breast carcinoma (NNBC). PATIENTS AND METHODS We monitored 254 consecutive patients with NNBC for a median of 62 months. Intratumoral MVD was measured after microvessels were immunostained using anti-CD31 antibody. p53 and c-erbB-2 protein and hormone receptors were also determined immunocytochemically. Results were analyzed by both univariate and multivariate statistical analysis. RESULTS Univariate analysis showed that MVD was significantly predictive of both RFS (odds ratio [OR], 8.30; P = .0001) and OS (OR, 4.50; P = .012) when tested as a continuous or dichotomous variable. Likewise, tumor size (OR, 3.16; P = .0012), PLVI (OR, 4.36; P = .0009), estrogen receptor (ER) status (OR, 2.35; P = .016), progesterone receptor (PR) status (OR, 2.00; P = .017), and expression of p53 protein (OR, 2.82; P = .004) were significantly associated with RFS. Tumor size (OR, 3.80; P = .0038) and expression of p53 protein (OR, 2.58; P = .024) were significantly associated with OS by univariate analysis. Multivariate analysis showed that MVD (P = .0004), p53 protein expression (P = .0063), tumor size (P = .0144), and PLVI (P = .0033) were all significant and independent prognostic factors for RFS. However, only tumor size (P = .004) and MVD (P = .047) were independent predictors for OS. c-erbB2 expression was not associated with outcome by either univariate or multivariate analysis. CONCLUSION MVD, p53 expression, PLVI, and tumor size are independent prognostic indicators of recurrence, which are useful in selection of high-risk NNBC patients who may be eligible to receive adjuvant therapies.

Aims and Background In spite of the fact that ductal carcinoma in situ (DCIS) of the breast is a frequently encountered clinical problem, there is no consensus about the optimal treatment of clinically occult (i.e., mammographic presentation only) DCIS. Interest in breast conservation therapy has recently increased. Few data are available in Italy on the conservative treatment with surgery and adjuvant postoperative radiotherapy. Methods A retrospective multi-institutional study was performed in 15 Radiation Oncology Departments in northern Italy involving 112 women with subclinical DCIS of the breast treated between 1982 and 1993. Age of the patients ranged between 32 and 72 years (median, 50 years). All of them underwent conservative surgery: quadrantectomy in 89, tumorectomy in 11, and wide excision in 12 cases. The most common histologic subtype was comedocarcinoma (37%). The median pathologic size was 10 mm (range 1 to 55 mm). Axillary dissection was performed in 83 cases: all the patients were node negative. All the patients received adjunctive radiation therapy with 60Co units (77%) or 6 MV linear accelerators (23%) for a median total dose to the entire breast of 50 Gy (mean, 49.48 Gy; range, 45-60 Gy). Seventy-six cases (68%) received a boost to the tumor bed at a dose of 8-20 Gy (median 10 Gy) for a minimum tumor dose of 58 Gy. Results At a median follow-up of 66 months, 8 local recurrences were observed, 4 intraductal and 4 invasive. All recurrent patients had a salvage mastectomy and are alive and free of disease at this writing. The 10-year actuarial overall, cause-specific, and recurrence-free survival was of 98.8%, 100%, and 91%, respectively. Conclusions The retrospective multicentric study, with a local control rate of more than 90% at 10 years with 100% cause-specific survival, showed that conservative surgery and adjuvant radiation therapy is a safe and efficacious treatment for patients with occult, non-palpable DCIS.

Purpose The combination of hyperthermia (HT) with radio(chemo)therapy or chemotherapy (CT) is an established treatment strategy for specific indications. Its application in routine clinical practice in Europe depends on regulatory and local conditions. We conducted a survey among European clinical centers to determine current practice of HT. Methods A questionnaire with 22 questions was sent to 24 European HT centers. The questions were divided into two main categories. The first category assessed how many patients are treated with HT in combination with radio(chemo)therapy or CT for specific indications per year. The second category addressed which hyperthermia parameters are recorded. Analysis was performed using descriptive methods. Results The response rate was 71% (17/24) and 16 centers were included in this evaluation. Annually, these 16 centers treat approximately 637 patients using HT in combination with radio(chemo)therapy or CT. On average, 34% (range: 3–100%) of patients are treated in clinical study protocols. Temperature readings and the time interval between HT and radio(chemo)therapy or CT are recorded in 13 (81%) and 9 (56%) centers, respectively. The thermal dose quality parameter “cumulative equivalent minutes at 43 °C” (CEM43°C) is only evaluated in five (31%) centers for each HT session. With regard to treatment sequence, 8 (50%) centers administer HT before radio(chemo)therapy and the other 8 in the reverse order. Conclusion There is a significant heterogeneity among European HT centers as to the indications treated and the recording of thermometric parameters. More evidence from clinical studies is necessary to achieve standardization of HT practice.