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Purpose: Hybrid image-guided surgery technologies such as combined radio- and fluorescence-guidance are increasingly gaining interest, but their added value still needs to be proven. In order to evaluate if and how fluorescence-guidance can help realize improvements beyond the current state-of-the-art in sentinel node (SN) biopsy procedures, use of the hybrid tracer indocyanine green (ICG)-99mTc-nancolloid was evaluated in a large cohort of patients.Patients and methods: A prospective trial was conducted (n = 501 procedures) in a heterogeneous cohort of 495 patients with different malignancies (skin malignancies, oral cavity cancer, penile cancer, prostate cancer and vulva cancer). After injection of ICG-99mTc-nanocolloid, SNs were preoperatively identified based on lymphoscintigraphy and SPECT/CT. Intraoperatively, SNs were pursued via gamma tracing, visual identification (blue dye) and/or near-infrared fluorescence imaging during either open surgical procedures (head and neck, penile, vulvar cancer and melanoma) or robot assisted laparoscopic surgery (prostate cancer). As the patients acted as their own control, use of hybrid guidance could be compared to conventional radioguidance and the use of blue dye (n = 300). This was based on reported surgical complications, overall survival, LN recurrence free survival, and false negative rates (FNR).Results: A total of 1,327 SN-related hotspots were identified on 501 preoperative SPECT/CT scans. Intraoperatively, a total number of 1,643 SNs were identified based on the combination of gamma-tracing (>98%) and fluorescence-guidance (>95%). In patients wherein blue dye was used (n = 300) fluorescence-based SN detection was superior over visual blue dye-based detection (22-78%). No adverse effects related to the use of the hybrid tracer or the fluorescence-guidance procedure were found and outcome values were not negatively influenced.Conclusion: With ICG-99mTc-nanocolloid, the SN biopsy procedure has become more accurate and independent of the use of blue dye. With that, the procedure has evolved to be universal for different malignancies and anatomical locations. [ABSTRACT FROM AUTHOR]

Background: Intraoperative radiotherapy (IORT) for locally advanced or recurrent rectal cancer as an integral part of multimodal treatment might be an option to reduce local cancer recurrence. The aim of the present study was to determine the influence of IORT on the postoperative outcome and complications rates in the treatment of patients with adenocarcinoma of the rectum in comparison to patients with rectum resection only. Methods: A total of 162 patients underwent operation for International Union against Cancer stage III/IV rectal cancer or recurrent rectal cancer at our surgical department between 2004 and 2012. They were divided into two groups depending on whether they received IORT or not. General patient details, tumor, and operation details, as well as perioperative major and minor complications, were registered and compared. Results: Of the 162 patients treated for stage III/IV rectal cancer, 52 underwent rectal resection followed by IORT. Complication rates were similar in the two groups. Operative time was significantly longer in the IORT group (248 ± 84 vs 177 ± 68 min; p < 0.001). No significant differences were found concerning anastomotic leakage rate, hospital stay, or wound infection rate. Conclusions: Intraoperative radiotherapy appears to be a safe treatment option in patients with locally advanced or recurrent rectal cancer with acceptable complication rates. The effect on local recurrence rate has to be estimated in long-term follow-up. [ABSTRACT FROM AUTHOR]

Background The TARGIT-A trial compared risk-adapted radiotherapy using single-dose targeted intraoperative radiotherapy (TARGIT) versus fractionated external beam radiotherapy (EBRT) for breast cancer. We report 5-year results for local recurrence and the first analysis of overall survival. Methods TARGIT-A was a randomised, non-inferiority trial. Women aged 45 years and older with invasive ductal carcinoma were enrolled and randomly assigned in a 1:1 ratio to receive TARGIT or whole-breast EBRT, with blocks stratified by centre and by timing of delivery of targeted intraoperative radiotherapy: randomisation occurred either before lumpectomy (prepathology stratum, TARGIT concurrent with lumpectomy) or after lumpectomy (postpathology stratum, TARGIT given subsequently by reopening the wound). Patients in the TARGIT group received supplemental EBRT (excluding a boost) if unforeseen adverse features were detected on final pathology, thus radiotherapy was risk-adapted. The primary outcome was absolute difference in local recurrence in the conserved breast, with a prespecified non-inferiority margin of 2 • 5% at 5 years; prespecified analyses included outcomes as per timing of randomisation in relation to lumpectomy. Secondary outcomes included complications and mortality. This study is registered with ClinicalTrials.gov, number NCT00983684. Findings Patients were enrolled at 33 centres in 11 countries, between March 24, 2000, and June 25, 2012.1721 patients were randomised to TARGIT and 1730 to EBRT. Supplemental EBRT after TARGIT was necessary in 15-2% [239 of 1571] of patients who received TARGIT (21-6% prepathology, 3-6% postpathology). 3451 patients had a median follow-up of 2 years and 5 months (IQR 12-52 months), 2020 of 4 years, and 1222 of 5 years. The 5-year risk for local recurrence in the conserved breast was 3-3% (95% CI 2 1-5 1) for TARGIT versus 1-3% (0-7-2-5) for EBRT (p=0-042). TARGIT concurrently with lumpectomy (prepathology, n=2298) had much the same results as EBRT: 2-1% (1-1-4-2) versus 1-1% (0-5-2-5; p=0-31). With delayed TARGIT (postpathology, n=1153) the between-group difference was larger than 2• 5% (TARGIT 5 ¦ 4% [3 • 0-9 • 7] vs EBRT 1 • 7% [0 • 6-4• 9]; p=0 • 069). Overall, breast cancer mortality was much the same between groups (2 ¦ 6% [1 ¦ 5-4 • 3] for TARGIT vs 1 ¦ 9% [1 • 1-3 • 2] for EBRT; p=0 • 56) but there were significantly fewer non-breast-cancer deaths with TARGIT (1 • 4% [0 ¦ 8-2 • 5] vs 3 • 5% [2 • 3-5 • 2]; p=0 • 0086), attributable to fewer deaths from cardiovascular causes and other cancers. Overall mortality was 3-9% (2-7-5-8) for TARGIT versus 5-3% (3-9-7-3) for EBRT (p=0 099). Wound-related complications were much the same between groups but grade 3 or 4 skin complications were significantly reduced with TARGIT (four of 1720 vs 13 of 1731, p=0 029). Interpretation TARGIT concurrent with lumpectomy within a risk-adapted approach should be considered as an option for eligible patients with breast cancer carefully selected as per the TARGIT-A trial protocol, as an alternative to postoperative EBRT. [ABSTRACT FROM AUTHOR]

Background The randomized TARGIT trial comparing experimental intra-operative radiotherapy (IORT) to up to 7 weeks of daily conventional external beam radiotherapy (EBRT) recruited participants in Western Australia between 2003 and 2012. We aimed to understand preferences for this evolving radiotherapy treatment for early breast cancer (EBC) in health professionals, and how they changed over time and in response to emerging data. Preferences for single dose IORT or EBRT for EBC were elicited in 2004 and 2011, together with factors that may be associated with these preferences. Methods Western Australian health professionals working with breast cancer patients were invited to complete a validated, self-administered questionnaire. The questionnaire used hypothetical scenarios and trade-off methodology to determine the maximum increase in risk of local recurrence health professionals were willing to accept in order to have a single dose of IORT in the place of EBRT if they were faced with this decision themselves. Results Health professional characteristics were similar across the two time points although 2011 included a higher number of nurse (49% vs. 36%) and allied health (10% vs. 4%) participants and a lower number of radiation therapists (17% vs. 32% ) compared to 2004. Health professional preferences varied, with 7.5% and 3% judging IORT unacceptable at any risk, 18% and 21% judging IORT acceptable only if offering an equivalent risk, 56% and 59% judging IORT acceptable with a low maximum increase in risk (1-3%) and 19% and 17% judging a high maximum increase in risk acceptable (4-5%), in 2004 and 2011 respectively. A significantly greater number of nurses accepted IORT as a treatment option in 2011. Conclusions Most Western Australian health professionals working with breast cancer patients are willing to accept an increase in risk of local recurrence in order to replace EBRT with IORT in a hypothetical setting. This finding was consistent over two time points spanning 7 years despite the duration of clinical experience with IORT and the publication of the early clinical results of IORT in 2010. These results need to be compared with preferences elicited from patient groups, and further investigation into the impact of personal preferences on health professionals' advice to patients is warranted. [ABSTRACT FROM AUTHOR]

BACKGROUND: Intraoperative radiation therapy (IORT) allows delivery of high-dose radiation at the time of lumpectomy, potentially sparing adjuvant daily radiation. A phase 2 study of pre-excision IORT was performed for early-stage breast cancer. METHODS: Patients ≥ 48 years of age with invasive ductal carcinoma, ≤ 3 cm, and clinically node-negative were eligible for this study, which was approved by institutional review board. Ultrasound was used to select electron energy and cone size to cover the tumor plus 1.5- to 2.0-cm lateral margins and 1-cm-deep margins (90% isodose). Fifteen Gy was delivered with a Mobetron irradiator, and immediate needle-localized partial mastectomy followed. Local event results were updated using the Kaplan-Meier method. RESULTS: A total of 53 patients received IORT alone. Median age was 63 years, and median tumor size was 1.2 cm. Of these, 81% were positive for estrogen receptor or progesterone receptor, 11% were positive for human epidermal growth factor receptor 2, and 15% were triple-negative. Also, 42%, 49%, and 9% would have fallen into the Suitable, Cautionary, and Unsuitable groups, respectively, of the American Society of Therapeutic Radiation Oncology consensus statement for accelerated partial breast irradiation. Median follow-up was 69 months. Ipsilateral events occurred in 8 of 53 patients. The 6-year actuarial rate of ipsilateral events was 15% (95% confidence interval = 7%-29%). The crude event rate for Suitable and Cautionary groups was 1 of 22 (5%) and 7 of 26 (27%), respectively. Overall survival was 94.4%, and breast cancer-specific survival was 100%. CONCLUSIONS: The rate of local events in this study is a matter of concern, especially in the Cautionary group. On the basis of these findings, pre-excision IORT, as delivered in this study, may not provide adequate local control for less favorable early-stage breast cancers. Cancer 2013. © 2013 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: The precise contribution of IORT to the management of locally advanced and recurrent colorectal cancer (CRC) remains uncertain. We performed a systematic review and meta-analysis to assess the value of IORT in this setting. Methods: Studies published between 1965 and 2011 that reported outcomes after IORT for advanced or recurrent CRC were identified by an electronic literature search. Studies were assessed for methodological quality and design, and evaluated for technique of IORT delivery, oncological outcomes, and complications following IORT. Outcomes were analysed with fixed-effect and random-effect model meta-analyses and heterogeneity and publication bias examined. Results: 29 studies comprising 14 prospective and 15 retrospective studies met the inclusion criteria and were assessed, yielding a total of 3003 patients. The indication for IORT was locally advanced disease in 1792 patients and locally recurrent disease in 1211 patients. Despite heterogeneity in methodology and reporting practice, IORT is principally applied for the treatment of close or positive margins. When comparative studies were evaluated, a significant effect favouring improved local control (OR 0.22; 95% CI = 0.05-0.86; p = 0.03), disease free survival (HR 0.51; 95% CI = 0.31-0.85; p = 0.009), and overall survival (HR 0.33; 95% CI = 0.2-0.54; p = 0.001) was noted with no increase in total (OR 1.13; 95% CI = 0.77-1.65; p = 0.57), urologic (OR 1.35; 95% CI = 0.84-2.82; p = 0.47), or anastomotic complications (OR 0.94; 95% CI = 0.42-2.1; p = 0.98). Increased wound complications were noted after IORT (OR 1.86; 95% CI = 1.03-3.38; p = 0.049). Conclusions: Despite methodological weaknesses in the studies evaluated, our results suggest that IORT may improve oncological outcomes in advanced and recurrent CRC. [ABSTRACT FROM AUTHOR]

Neoadjuvant chemoradiation (CRT), tailored mesorectal excision, and intraoperative radiotherapy (IORT) have become the leading measures for rectal cancer treatment. The objective of this study was to evaluate early and long-term results of a multimodal treatment model for rectal cancer followed by curative surgery. Prospectively collected hospital records of 338 patients surgically treated for rectal cancer between January 1998 and December 2008 were retrospectively reviewed. Patients with high rectum level cancers and those with middle and low rectum cancers with clinical stage T1 to T2 underwent surgery, whereas those with T3 to T4 and N+ disease at the middle and low rectum received neoadjuvant CRT in 96.2 per cent of cases. Short-course neoadjuvant radiotherapy was not considered for neoadjuvant treatment. Postoperative major complications and mortality rates were 12.7 and 2.3 per cent, respectively. Overall 5-year disease-specific and disease-free survival were 80 and 73.1 per cent, respectively, whereas local recurrence rate was 6.1 per cent. At multivariate analysis, nodal status and circumferential margin status were independently associated with poor survival; local recurrence rates were independently affected by nodal and marginal status and tumor stage. The extent of mesorectal excision should be tailored depending on tumor location and the use of neoadjuvant chemotherapy, combined with IORT in advanced middle and low rectal cancer, leading to remarkable tumor downstaging with excellent prognosis in responding patients. [ABSTRACT FROM AUTHOR]

Background: The purpose of the study is to evaluate the long-term clinical outcome through biochemical no evidence of disease (bNED) rates among men with low to intermediate risk prostate cancer treated with two different brachytherapy implant techniques: preoperative planning (PP) and real-time planning (IoP).Methods: From June 1998 to July 2011, 1176 men with median age of 67 years and median follow-up of 47 months underwent transperineal ultrasound-guided prostate ¹²⁵I-brachytherapy using either PP (132) or IoP (1044) for clinical T1c-T2b prostate adenocarcinoma Gleason <8 and prostate-specific antigen (PSA) <20 ng/ml. Men with Gleason 7 received combination of brachytherapy, external beam radiation and 6-month androgen deprivation therapy (ADT). Biological effective dose (BED) was calculated using computerized tomography (CT)-based dosimetry 1-month postimplant. Failure was determined according to the Phoenix definition.Results: The 5- and 7-year actuarial bNED rate was 95% and 90% respectively. The 7-year actuarial bNED was 67% for the PP group and 95% for the IoP group (P < 0.001). Multivariate Cox regression analyses identified implant technique or BED, ADT and PSA as independent prognostic factors for biochemical failure.Conclusions: Following our previous published results addressing the limited and disappointing outcomes of PP method when compared to IoP based on CT dosimetry and PSA kinetics, we now confirm the long-term clinical, bNED rates clear cut superiority of IoP implant methodology. [ABSTRACT FROM AUTHOR]

In accelerated partial breast irradiation (APBI), the most commonly used fractionation schemes include 340 or 385 centigrays delivered in a twice daily administration. A further progression of the APBI literature has been the recent interest in extremely short courses of adjuvant radiotherapy, usually delivered by intraoperative radiotherapy techniques. This newer area of single-fraction radiotherapy approaches remains highly contentious. In particular, the recently reported TARGIT trial has been the subject of both praise and scorn, and a critical examination of the trial data and the underlying hypotheses is warranted. Short-term outcomes of the related Italian ELIOT approach have also been reported. Although the assumptions of linear quadratic formalism are likely to hold true in the range of 2 to 8 grays, equating different schedules beyond this range is problematic. A major problem of current single-fraction approaches is that the treatment doses are chosen empirically, or are based on tolerability, or on the physical dose delivery characteristics of the chosen technology rather than radiobiological rationale. This review article summarizes the current data on ultrashort courses of adjuvant breast radiotherapy and highlights both the promise and the potential pitfalls of the abbreviated treatment. Cancer 2012. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

Summary: Introduction: GBM has a poor survival despite surgery and chemoradiotherapy. Cytoreduction and PDT have postulated to afford better local GBM-control. However, the interaction of PDT with newer novel therapies had not been fully investigated. This study reviewed the impact of PDT in conjunction with intraoperative radiotherapy. Methods: Case note review of prospectively collected data of GBMs treated surgically by the senior author (SE). Patients received standard therapy (ST), ST+PDT or ST+PDT+IORT. ST involved maximum safe resection, PDT involved intracavity 100J/cm2 630nm laser and IORT involved intracavity 10–15Gys using the PRS400®. Patients were followed up clinically and radiologically till death. Results: There were 73 patients included in this analysis (42 males). The average age was 59years. Thirty received PDT and 43 did not. The mean survival of PDT-patients was significantly longer than those had ST alone (62.9weeks vs. 20.6weeks) (p =0.001). Patients <65year of age survived longer than those ≥65year (p =0.033). IORT on its own did not make a significant difference to survival (p =0.111). However the average survival for patients who received PDT+IORT was substantially higher than those who received PDT alone (79weeks vs. 39.7weeks). Using a Cox regression covariant analysis, demonstrated that PDT was the only therapy to make a statistically significant difference to survival (p =0.018). Conclusions: PDT in high grade glioma was statistically significant therapeutic modality and its effects were further improved by IORT. [Copyright &y& Elsevier]

Intraoperative electron beam radiotherapy (IOERT) for prostate cancer (PC) is a radiotherapeutic technique, giving high doses of radiation during radical prostatectomy (RP). This paper presents the published treatment approaches for intraoperative radiotherapy analyzing functional outcome, morbidity, and oncological outcome in patients with clinical intermediate-high-risk prostate cancer. A systematic review of the literature was performed, searching PubMed andWeb of Science. A "free text" protocol using the term intraoperative radiotherapy and prostate cancer was applied. Ten records were retrieved and analyzed including more than 150 prostate cancer patients treated with IOERT. IOERT represents a feasible technique with acceptable surgical time and minimal toxicity. A greater number of cases and longer follow-up time are needed in order to assess the long-term side effects and oncological outcome. [ABSTRACT FROM AUTHOR]

Abstract: Intraoperative radiotherapy (IORT) has been proposed as an encouraging treatment for colorectal cancer. The aim of this study is to assess the efficacy and safety of IORT for this cancer through a systematic review. Studies located in electronic databases were selected according to established criteria, read and analysed and the results extracted by two independent reviewers. Fifteen studies met the selection criteria. Five-to-six-year local control (LC) was over 80% and 5-year overall survival (OS) was close to 65%. For recurrences, the 5-year overall survival was 30%. The main acute complications were gastrointestinal. Adding IORT to conventional treatment reduces the incidence of local recurrences within the radiation area over 10%. IORT is a safe technique as it does not increase toxicity associated with conventional treatment. [Copyright &y& Elsevier]

Purpose: To retrospectively analyze the results of intraoperative radiotherapy (IORT) + external beam radiotherapy (EBRT) for unresectable pancreatic cancer. Methods and Materials: The records of 144 patients treated with IORT, with or without, EBRT were reviewed. One hundred and thirteen patients (78.5%) were treated with IORT + EBRT and 114 patients (79.2%) were treated in conjunction with chemotherapy. The median doses of IORT and EBRT were 25 Gy and 45 Gy, respectively. The median follow-up of all 144 patients was 9.6 months (range, 0.5–69.7 months). Results: At the time of this analysis, 131 of 144 patients (91.0%) had disease recurrences. Local progression was observed in 60 patients (41.7%), and the 2-year local control (LC) rate in all patients was 44.6%. Patients treated with IORT, with or without, EBRT had significantly more favorable LC (2-year LC, 50.9%) than those treated with IORT without EBRT (p = 0.0004). The 2-year overall survival (OS) rate and the median survival time in all 144 patients were 14.7% and 10.5 months, respectively. Patients treated with chemotherapy had a significantly favorable OS than those treated without chemotherapy (p < 0.0001). On univariate analysis, chemotherapy use alone had a significant impact on OS and on multivariate analysis; chemotherapy use was a significant prognostic factor. Late gastrointestinal morbidity of National Cancer Institute-Common Terminology Criteria Grade 3 was observed in 2 patients (1.4%). Conclusion: IORT + EBRT yields a relatively favorable LC rate for unresectable pancreatic cancer with low frequency of severe late toxicity, and IORT combined with chemotherapy conferred a survival benefit compared with IORT without chemotherapy. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Conventional lymphoscintigraphy provides planar images with little spatial information on location of pelvic sentinel lymph nodes (SLN). SPECT has better spatial resolution and, in combination with anatomic accuracy provided by CT improves SLN preoperative localization. The aim of the study was to report on the results of hybrid imaging of SLN in early cervical cancer patients treated at Claudius Regaud Cancer Center. Methods: Stages IA–IB1 cervical cancer patients undergoing preoperative SPECT/CT for SLN detection were analysed. Results: Forty-one patients were included. A 100% SLN detection rate was achieved when a combined technique (radiotracer and blue dye) was used. At least one SLN was clearly visualized by SPECT/CT in 39 of 41 patients (95%) and full anatomic concordance with intraoperative anatomical location of SLN was found in 37 of the 39 patients with at least one SLN identified by SPECT/CT (95%). Location of removed SLN included the external and internal iliac area in 88% patients, the common iliac area in 10.5%, and the inframesenteric para-aortic area in 1.5%. No SLN was found in the infrarenal para-aortic region. Lymph node involvement was identified in 5 patients (12.1%). SLN correctly predicted lymph node involvement in all node-positive patients. However, SPECT/CT failed to identify 1 of the 5 metastatic SLN. Discussion: SPECT/CT accurately detected preoperative SLN topography and enhanced diagnostic sensitivity of SLN imaging, improving surgical approach to patients with cervical cancer staging. Diagnostic quality of anatomic landmarks of CT images of SPECT/CT could be further improved by the use of contrast injected CT. [Copyright &y& Elsevier]

Background: The purpose of this study is to analyze the pooled results of multimodality treatment of locally advanced rectal cancer (LARC) in four major treatment centers with particular expertise in intraoperative radiotherapy (IORT). [ABSTRACT FROM PUBLISHER]

Abstract: The addition of conventional whole breast irradiation (WBI) to breast conserving surgery (BCS) reduces the risk of early breast cancer recurrence and leads to a statistically and clinically significant improvement in overall survival. However, the long duration of conventional WBI regimens negatively impacts on quality of life. This has led investigators to evaluate an alternative approach of delivering radiation to a limited volume of tissue around the tumour cavity only (partial breast irradiation) and delivering a larger than standard dose of radiation with each treatment (accelerated partial breast irradiation, APBI). This approach may be achieved by a number of techniques: interstitial brachytherapy, intracavitary brachytherapy using the Mammosite device, intraoperative techniques using electrons or low-energy photons, external beam radiotherapy or permanent seed implant. This articles will review the rationale for the less that whole breast radiotherapy approach and describe the techniques by which it can be achieved and the results obtained to date. Finally, the 7 prospective randomised controlled trials of conventional WBI versus APBI which are open and currently recruiting patients will be discussed. [Copyright &y& Elsevier]

Purpose: We analyzed our experience with intraoperative electron radiotherapy (IOERT) followed by moderate doses of external beam radiotherapy (EBRT) after organ-sparing surgery in patients with primary or recurrent aggressive fibromatosis. Methods and Materials: Indication for IOERT and postoperative EBRT as an individual treatment approach to avoid mutilating surgical procedures was seen when complete surgical removal seemed to be unlikely or impossible. A total of 31 lesions in 30 patients were treated by surgery and IOERT with a median dose of 12 Gy. Median age was 31 years (range, 13–59 years). Resection status was close margin in six lesions, microscopically positive in 13, and macroscopically positive in 12. Median tumor size was 9 cm. In all, 25 patients received additional EBRT, with a median dose of 45 Gy (range, 36–54 Gy). Results: After a median follow-up of 32 months (range, 3–139 months), no disease-related deaths occurred. A total of five local recurrences were seen, resulting in actuarial 3-year local control rates of 82% overall and 91% inside the IOERT areas. Trends to improved local control were seen for older age (>31 years) and negative margins, but none of these factors reached significance. Perioperative complications were found in six patients, in particular as wound healing disturbances in five patients and venous thrombosis in one patient. Late toxicity was seen in five patients. Conclusion: Introduction of IOERT into a multimodal treatment approach in patients with aggressive fibromatosis is feasible with low toxicity and yielded good local control rates even in patients with microscopical or gross residual disease. [Copyright &y& Elsevier]

Purpose: To report the use of high-dose-rate intraoperative radiation therapy (HDR-IORT) for recurrent head-and-neck cancer (HNC) at a single institution. Methods and Materials: Between July 1998 and February 2007, 34 patients with recurrent HNC received 38 HDR-IORT treatments using a Harrison-Anderson-Mick applicator with Iridium-192. A single fraction (median, 15 Gy; range, 10–20 Gy) was delivered intraoperatively after surgical resection to the region considered at risk for close or positive margins. In all patients, the target region was previously treated with external beam radiation therapy (median dose, 63 Gy; range, 24–74 Gy). The 1- and 2-year estimates for in-field local progression-free survival (LPFS), locoregional progression-free survival (LRPFS), distant metastases-free survival (DMFS), and overall survival (OS) were calculated. Results: With a median follow-up for surviving patients of 23 months (range, 6–54 months), 8 patients (24%) are alive and without evidence of disease. The 1- and 2-year LPFS rates are 66% and 56%, respectively, with 13 (34%) in-field recurrences. The 1- and 2-year DMFS rates are 81% and 62%, respectively, with 10 patients (29%) developing distant failure. The 1- and 2-year OS rates are 73% and 55%, respectively, with a median time to OS of 24 months. Severe complications included cellulitis (5 patients), fistula or wound complications (3 patients), osteoradionecrosis (1 patient), and radiation-induced trigeminal neuralgia (1 patient). Conclusions: HDR-IORT has shown encouraging local control outcomes in patients with recurrent HNC with acceptable rates of treatment-related morbidity. Longer follow-up with a larger cohort of patients is needed to fully assess the benefit of this procedure. [Copyright &y& Elsevier]

Purpose: To analyze the feasibility of intraoperative radiotherapy (IORT) in patients with high-risk prostate cancer and candidates for radical prostatectomy. Methods and Materials: A total of 38 patients with locally advanced prostate cancer were enrolled. No patients had evidence of lymph node or distant metastases, probability of organ-confined disease >25%, or risk of lymph node involvement >15% according to the Memorial Sloan-Kettering Cancer Center Nomogram. The IORT was delivered after exposure of the prostate by a dedicated linear accelerator with beveled collimators using electrons of 9 to 12 MeV to a total dose of 10-12 Gy. Rectal dose was measured in vivo by radiochromic films placed on a rectal probe. Adminstration of IORT was followed by completion of radical prostatectomy and regional lymph node dissection. All cases with extracapsular extension and/or positive margins were scheduled for postoperative radiotherapy. Patients with pT3 to pT4 disease or positive nodes received adjuvant hormonal therapy. Results: Mean dose detected by radiochromic films was 3.9 Gy (range, 0.4–8.9 Gy) to the anterior rectal wall. The IORT procedure lasted 31 min on average (range, 15–45 min). No major intra- or postoperative complications occurred. Minor complications were observed in 10/33 (30%) of cases. Of the 27/31 patients who completed the postoperative external beam radiotherapy, 3/27 experienced Grade 2 rectal toxicity and 1/27 experienced Grade 2 urinary toxicity. Conclusions: Use of IORT during radical prostatectomy is feasible and allows safe delivery of postoperative external beam radiotherapy to the tumor bed without relevant acute rectal toxicity. [Copyright &y& Elsevier]

Background: The present study was designed to identify the optimal intraoperative radiotherapy (IORT) dose for early breast cancer in Japanese women. Methods: A phase I study was designed using a scheme of dose-escalation from 19, 20, and 21 Gy at 90% isodose. The primary endpoint was early toxicity. Secondary endpoints were efficacy for a long period and late toxicity. Inclusion criteria were as follows: (1) tumor size <2.5 cm, (2) age >50 years, (3) surgical margin >1 cm, (4) intraoperative pathologically free margins, (5) written informed consent. Exclusion criteria were (1) contraindication to radiation therapy, (2) extensive intraductal component. Partial resection was performed with at least a 1-cm margin around the tumor. Radiation was delivered directly to the mammary gland employing a MOBETRON device. Toxicity was evaluated with the Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Results: From December 2007 to September 2008, 9 patients were enrolled in the study. The first three patients received a radiation dose of 19 Gy. Within 3 months toxicity in each case was deep connective tissue fibrosis (grade 1: 2/3, grade 2: 1/3). The next three patients received a dose of 20 Gy and had toxicities of deep connective tissue fibrosis (grade 1: 3/3), hematoma (grade 1: 2/3), infection in the musculoskeletal soft tissue (grade 1: 2/3), and soft tissue necrosis (grade 2: 1/3). The final three patients received a dose of 21 Gy and had toxicities of deep connective tissue fibrosis (grade 1: 2/3), hematoma (grade 1: 1/3), infection in the musculoskeletal soft tissue (grade 1: 1/3), and soft tissue necrosis (grade 2: 2/3). Conclusions: The IORT treatment was tolerated very well in Japanese women, and we now recommend the dose of 21 Gy. [ABSTRACT FROM AUTHOR]

Purpose: To analyze results of multimodality treatment in relation to subsite of locally recurrent rectal cancer (LRRC). Method and Materials: A total of 170 patients with LRRC who underwent treatment between 1994 and 2008 were studied. The basic principle of multimodality treatment was preoperative (chemo)radiotherapy, intended radical surgery, and intraoperative radiotherapy. The subsites of LRRC were classified as presacral, posterolateral, (antero)lateral, anterior, anastomotic, or perineal. Subsites were related to radicality of the resection, local re-recurrence rate, distant metastasis rate, and cancer-specific survival. Results: R0 resections were achieved in 54% of the patients, and 5-year cancer-specific survival was 40.5%. The worst outcomes were seen in presacral LRRC, with only 28% complete resections and 19% 5-year survival (p = 0.03 vs. other subsites). Anastomotic LRRC resulted in the most favorable outcomes, with 77% R0 resections and 60% 5-year survival (p = 0.04). Generally, if a complete resection was achieved, survival improved, except in posterolateral LRRC. Local re-recurrence and metastasis rate were lowest in anastomotic LRRC. Conclusions: Classification of the subsite of LRRC is a predictor of potentially resectable and consequently curable disease. Treatment of posterior LRRC imposes poor results, whereas anastomotic LRRC location shows superior results. [Copyright &y& Elsevier]

Abstract: Objective: To investigate the feasibility of intra-operative radiation therapy (IORT) in hepato-cellular carcinoma (HCC). Methods: Based on the dosage distribution of tumor and adjacent sensitive organs, and dose-volume histogram (DVH), Topslane three-dimensional therapy plan was used to compare IORT and three-dimensional conformal radiation therapy (3D-CRT) in 12 cases of HCC. Results: Taking the center of tumors as the isodose center, the V90 (volume of 90% dose distribution) of IORT was significantly better than that of 3D-CRT, and median absorbed doses of normal organs in IORT was significantly lower than that in 3D-CRT. Conclusion: The V90 of IORT is better than that of 3D-CRT in HCC, and neighboring sensitive organs were effectively protected by IORT. The tumors absorbed dose and local control rate are improved in IORT. [Copyright &y& Elsevier]

Abstract: The purpose of this study was to assess mammographic and sonographic findings in a long-term follow-up (≥3 years) after breast-conserving surgery (BCS) and IORT, either applied as boost or exclusively. Follow-up-findings of 54 patients were retrospectively evaluated and compared to a control group of 48 patients, treated with BCS and whole-breast radiotherapy. After IORT patients had a higher incidence of fat necroses manifesting as oil cysts in the late follow-up mammograms (n = 31 vs n = 8); furthermore, oil cysts were larger in the IORT group (median 4.5 vs 1.4 cm2). In 25 IORT patients the oil cysts arose from partially organized hematomas/seromas, which in this group were generally more frequent (n = 38 vs n = 9) and larger (median 3.6 vs 1.8 cm2). After IORT a decreasing incidence of hematomas/seromas was reciprocal to an increasing incidence of oil cysts, and the size of both entities correlated with each other. Liquid lesions with polypoid inner wall thickening on ultrasound, attributed to organized hematomas/seromas or fat necroses, appear more frequently after IORT (n = 15 vs n = 1). In conclusion, IORT is associated with a high incidence of large oil cysts, which arise from likewise large partially organized wound cavities. On ultrasound pronounced partial organization with polypoid inner wall thickening is a frequent finding in those cavities. [Copyright &y& Elsevier]

Abstract: Purpose: A joint analysis of data from five contributing centers within the ISIORT-Europe program was performed to investigate the main contributions of intra-operative radiotherapy (IORT) to the multidisciplinary treatment of pancreatic cancer. Materials and methods: Patients with a histologic diagnosis of carcinoma of the pancreas, with an absence of distant metastases, undergoing surgery with radical intent and IORT were considered eligible for participation in this study. Results: From 1985 to 2006, a total of 270 patients were enrolled in the study from five European Institutions. Surgery was performed in 91.5% of cases and complicated by adverse events in 59 cases. External radiotherapy (ERT) preceded surgery in 23.9% of cases. One-hundred and six patients received further ERT. After surgery+IORT, median follow-up was 96 months (range 3–180). Median local control was 15 months, 5-year local control was 23.3%. Median overall survival was 19 months, while 5-year survival was 17.7%. A significantly greater local control and survival were observed in patients undergoing preoperative radiotherapy (LC: median not reached; OS: median 30 months) compared to patients treated with postoperative ERT alone (LC: median 28 months; OS: median 22 months), and to patients submitted to IORT exclusively (LC: median 8 months; OS: median 13 months) (p <0.0001). Conclusion: From this joint analysis emerges the fact that preoperative radiotherapy increases the effects of IORT in terms of local control and overall survival. The 5-year local control of 23.3% confirms the beneficial “sterilizing” effect of IORT on the tumor bed. [Copyright &y& Elsevier]

Abstract Purpose  We investigated whether adjuvant immunotherapy with Bacillus Calmette-Guérin (BCG) cell wall skeleton (CWS) and surgical resection was better than resection, with or without other adjuvant therapy, for patients with non-small cell lung cancer (NSCLC). Methods  The case group comprised 71 patients who underwent radical surgery for NSCLC, followed by BCG-CWS immunotherapy, with follow-up data available. The case-control study was designed with one control selected for each case-group patient. Each control was matched by pathological stage and year of birth (±5 years). BCG-CWS 200 μg was inoculated intracutaneously in the upper arm four times per week (sensitization phase); then at 4-week intervals (therapeutic phase). Results  The case-group patients received 45 ± 22.6 (average ± SD) cycles of BCG-CWS inoculation. Overall 5-year and 10-year survival rates were 71% and 61% for the case-group patients, and 63% and 43% for the control-group patients. The survival rate of the case group was better than that of the control group (not significant; P = 0.114). The same trend was seen in the patients with stage III or N+ NSCLC (not significant; P = 0.114, P = 0.168). There were no life-threatening adverse events. Conclusions  BCG-CWS immunotherapy seemed to improve survival after resection of NSCLC, especially locally advanced NSCLC. Moreover, this immunotherapy did not compromise quality of life during treatment. [ABSTRACT FROM AUTHOR]

Abstract: Background: Intraoperative radiotherapy (IORT) during breast-conserving surgery is increasingly used. We analyzed the influence of the interval between an IORT boost and external beam radiotherapy (EBRT) on late toxicity. Methods: Forty-eight patients received 20Gy IORT (50kV X-rays (Intrabeam, Carl Zeiss, Oberkochen, Germany) followed by 46–50Gy EBRT with a median interval of 36days (14-197). Late toxicity was assessed with the modified LENT SOMA score after a median of 36months. Results: Twelve patients developed a higher grade fibrosis (°II–III), three teleangiectases, one a breast edema grade °II, six retractions, four hyperpigmentations and five pain (°II–III). The median interval between IORT and EBRT was significantly shorter in these patients (n =18) compared to the 30 patients without higher grade toxicity (29.5days vs. 39.5days, p =0.023, Mann–Whitney U-test). Conclusion: Starting EBRT about 5–6weeks after IORT appears to be associated with a decreased risk of chronic late toxicity compared with a shorter interval. The impact on local recurrence of prolonged gaps between IORT and EBRT is not known. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

The aim of this study was to evaluate mammographic and sonographic changes at the surgical site within the first 2 years after IORT as a boost followed by whole-breast radiotherapy (WBRT), compared with a control group treated with WBRT alone. All patients had breast-conserving surgery for early-stage breast cancer. Group A: n = 27, IORT (20 Gy) followed by WBRT (46 Gy). Group B (control group): n = 27, WBRT alone (56-66 Gy). Mammography: fat necrosis in 14 group A versus four group B patients (P < 0.001); parenchymal scarring classified as unorganized at the last follow-up in 16 vs seven cases, respectively (P = 0.03). Ultrasound: overall number of patients with circumscribed findings 27 vs 18 (P < 0.001); particular hematomas/seromas in 26 vs 13 patients (P < 0.001). Synopsis of mammography and ultrasound: overall postoperative changes were significantly higher classified in group A (P = 0.01), but not judged to have a significantly higher impact on interpretation. Additional diagnostic procedures, due to unclear findings at the surgical site, were performed on four patients of both groups. Within the first 2 years after IORT as a boost, therapy-induced changes at the original tumor site are significantly more pronounced compared with a control group. There is no evidence that the interpretation of findings is complicated after IORT. [ABSTRACT FROM AUTHOR]

PURPOSE: This study was designed to investigate the influence of intraoperative and postoperative radiotherapy on functional outcome after rectal resection for rectal cancer. METHODS: One hundred patients who underwent deep or standard anterior resection for rectal cancer were included in this follow-up study. All patients filled out questionnaires regarding morbidity and functional outcome; a subgroup (n = 63) underwent further clinical evaluation. The results were stratified according to radiation: Group I, no radiation (n = 37); Group II, only intraoperative radiation (n = 12); Group III, intraoperative and postoperative radiation (n = 51). RESULTS: Anal continence measured by Kirwan-Parks classification and Wexner score was significantly different within the three groups (P < 0.005, P < 0.0001), whereas continence impairment was least in Group I and greatest in Group III. Patients in Group III demonstrated a significantly worse category in the Kirwan-Parks classification and worse Wexner scores compared with patients in Group I (P < 0.0001). Patients only having undergone intraoperative radiotherapy had a significantly worse continence (Kirwan-Parks classification) than patients without any radiotherapy (P < 0.05). More patients after intraoperative and postoperative radiation therapy complained of fragmented stools (P < 0.05) and urgency (P < 0.05) compared with patients only having undergone surgery; the need to wear pads was higher (P = 0.001). Vector volume manometry revealed better resting sphincter function in Group I compared with Group III (P ≤ 0.005). CONCLUSIONS: Patients with anterior resection for rectal cancer who undergo full-dose radiotherapy have significantly more impairment of anorectal function than patients without radiotherapy. Patients who were only exposed to intraoperative radiotherapy showed moderate impairment of continence function, suggesting that the influence of radiotherapy on anal function may be dose-dependent and application-dependent. [ABSTRACT FROM AUTHOR]

Summary: Intraoperative radiotherapy (IORT) is a technique in which a high, single-fraction radiation dose is delivered directly to the tumour bed during a surgical intervention, after the removal of a neoplastic mass. IORT has been recently used in early stage cancer as an exclusive radiation modality, rather than as a boost, especially for breast tumours, in particular at the European Institute of Oncology in Milan, where the technique has been called electron intraoperative therapy (ELIOT). Our studies on more than 1000 patients have demonstrated the feasibility of the technique and it is expected that its application will become more widespread in the immediate future. It is important to emphasise that ELIOT relies not only on new technological developments, but also on a multidisciplinary team with clear roles and responsibilities, the establishment of a programme of quality assurance with appropriate guidelines and a comprehensive staff development programme. [Copyright &y& Elsevier]

The objective of this study is to investigate the treatment results, prognostic factors, the role of postoperative radiotherapy, and the usefulness of American Joint Committee on Cancer (AJCC) Staging System (2002) for soft tissue sarcomas in malignant fibrous histiocytoma (MFH). Between November 1987 and December 2000, 76 patients with localized MFH underwent surgery as the primary treatment modality with or without radiotherapy in our institution and were reviewed retrospectively. Patients with regional nodal disease, distant metastases or retroperitoneal disease were excluded from our study. All patients had at least 27 months of follow-up. The 5-year overall survival rate, local control rate, and distant metastasis-free rate were 74%, 62%, and 87%, respectively. In multivariate analysis, AJCC 2002 staging system was the only independent prognostic factor for overall survival rates (p=0.0017). Postoperative radiotherapy was the only significant factor for local control rates (p=0.0024). In conclusion, staging system is a prognostic predictor for overall survival rates and postoperative radiotherapy can improve local control. However, the optimal adjuvant treatment strategy for MFH should still be further explored. [ABSTRACT FROM AUTHOR]

Determines the intraoperative pathologic indicators used in discriminating a subgroup of early corpus cancer not requiring lymphadenectomy or radiotherapy. Surgical and pathologic characteristics of patients with low-risk endometrial cancer; Association of pelvic lymph node metastasis with primary tumor diameter; Recurrence and survival rates of low-risk patients.

Purpose. The purpose is to review the natural history, the clinicopathological prognostic factors, and the role of adjuvant radiation therapy with particular attention to the limited but favorable experience with IORT. Methods. Retroperitoneal sarcomas present a continuing therapeutic challenge to the oncologist. In contrast to sarcomas of the extremity and superficial trunk in which complete resection plus radiation therapy results in excellent local control, sarcomas of the retroperitoneum are difficult to resect and even if completely resected, demonstrate high rates of local relapse, the primary pattern of failure. Due to the proximity of normal organs, the delivery of therapeutic doses of adjuvant external beam radiation therapy is problematic.To deliver adequate doses (>60 Gy) of external beam to most patients would result in unacceptable toxicity. The therapeutic dilemma is unfortunate and better strategies are needed. One attractive approach has been to incorporate intraoperative radiation therapy (IORT) with maximal resection and external beam radiation. Results and Discussion. A number of institutions have explored this approach with encouraging preliminary results. [ABSTRACT FROM AUTHOR]

Reports on the mixed responses regarding intraoperative radiation for advanced cancer at the annual meeting of the Society of Surgical Oncology in Orlando, Florida. Benefits of intraoperative radiation; Clinical results of intraoperative radiation; Limitations and problems of intraoperative radiation; Alternative to intraoperative radiation.

Summary: This previously unreported renaissance painting depicts a young woman with locally advanced breast cancer reaching out towards a healing potion in the church of Santa Maria della Grazia in Milan, that houses Leonardo da Vinci''s Last supper. Today''s potion may well contain neoadjuvant systemic therapy including trastuzumab that may allow breast conserving surgery and targeted intraoperative radiotherapy. [Copyright &y& Elsevier]

Reports on the presentation of the study that intraoperative planning for permanent prostate seed implants is a technique that is used with excellent results at the annual meeting of the American Brachytherapy Society. Identification of the outcome of the technique; Separation of preoperative appointment; Number of seeds needed for the procedure. INSET: At a Glance.

Background. Angiogenesis is essential for tumor growth and development of breast cancer in early as well as in metastatic stage. There is a correlation between intratumoral angiogenesis and circulating levels of angiogenic factors. Method. A systematic revue of PubMed was performed to identify the prognostic and the predictive role of circulating angiogenic factors in breast cancer. Results. Plasma VEGF A levels correlate with tumour volume and are well established as an indicator of poor prognosis. Studies suggest that circulating levels of short vascular endothelial growth factor A (VEGF-A) isoforms, soluble VEGF receptor 1, IL8 and ANG 2 are strong biomarker candidates. Complementary changes in expression of PIGF, VEGF C, VEGF D, b-FGF, PDGF-BB and SDF1 were observed during Bevacizumab treatment. Increases in the levels of circulating bFGF, PDGF -BB, VEGF-C and VEGF-D were observed on progression. In BRCA1 mutated breast cancer there are preclinical evidence of VEGF, ANG1 and TSP1 angiogenic factors upregulation. In spite of a small improvement in OS in metastatic setting, the addition of Bevacizumab increased the rate of pathological complete response in hormone receptors negative patients. Baseline levels of VEGF do not reliably predict response to Bevacizumab but correlate with PFS in mBC. Pretreatment soluble VEGFR1 levels inversely correlated with outcome in AVADO trial. Short VEGF-A isoforms exhibit improved PFS and/or OS after bevacizumab. The tyrosin kinase antiangiogenics are under investigation in breast cancer: sorafenib in combination with chemotherapy or endocrine therapy, axitinib added to docetaxel, cediranib with fulvestrant, Vandetanib, but important toxicities were reported. An increase of IL8 and VEGF during Vandetanib therapy and a concurrent decrease of sVEGFR2 were noticed. Conclusion. There are candidate biomarkers with possible clinical prognostic and predictive interest. Obviously, it remains the feasibility challenge. [ABSTRACT FROM AUTHOR]

Discusses research on intraoperative radiotherapy in resected pancreatic cancer. Reference to a study by R. Coquard et al., published in a 1997 issue of the journal "Radiotherapy Oncology"; Study procedure; Study findings.

The author argues against the support of the British government for alternative medicine. He cites the decision of the Great Britain Department of Health to reject the proposal of the House of Commons Science and Technology Committee to stop financing homeopathy in the National Health Service (NHS). He argues that saving the money spent on homeopathy could open intraoperative radiotherapy service for all breast cancer patients in England and Wales.

Summary: The introduction of innovative radiotherapy approaches for early breast cancer patients is rapidly changing the radiation oncologists'' attitude and their expectations to obtain a good local control while decreasing morbidity therefore improving patient''s quality of life. Intraoperative radiotherapy is a very attractive treatment modality in the multidisciplinary approach to breast conservation as is testified by the rapidly growing number of patients accrued in numerous studies all over Europe since 2000. A major advantage of intraoperative radiotherapy in breast cancer treatment is the administration of a large dose of radiation directly to the tumour bed, avoiding the possible geographic miss. Accurate localization and precise definition of the tumour bed volume is essential to achieve maximal efficacy in terms of local control while minimizing unnecessary damage to the normal breast tissue. Intraoperative radiotherapy reduces radiation exposure of the skin, lung, heart and normal subcutaneous tissues thus contributing to the low incidence of side effects and the generally excellent cosmetic results. Compared to other intraoperative techniques, the superiority of intraoperative radiotherapy appears to be the high homogeneity of dose distribution. The linear quadratic model used to calculate the biologic equivalent dose of intraoperative radiotherapy treatments for both tumour and normal tissue effects, is not considered totally reliable for large dose per fraction. The main concern is the potential increase in severe late side effects. Conversely, we expect an enhanced local control due to the radiobiologic efficacy of a large single dose delivered soon after tumour excision, with an immediate cell killing effect over any potential microscopic disease. The advantage of shortening the overall treatment time is that it avoids any delay in the administration of chemotherapy. The safety of intraoperative radiotherapy as a treatment modality in the context of breast conservation has been proved but conclusive data on local control and survival are expected from long term results of the ongoing studies. [Copyright &y& Elsevier]