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To quantify the dosimetric impact of contouring variability of axillary lymph nodes (L2, L3, L4) in breast cancer (BC) locoregional radiotherapy (RT).18 RT centres were asked to plan a locoregional treatment on their own planning target volume (single centre, SC-PTV) which was created by applying their institutional margins to the clinical target volume of the axillary nodes of three BC patients (P1, P2, P3) previously delineated (SC-CTV). The gold standard CTVs (GS-CTVs) of P1, P2 and P3 were developed by BC experts' consensus and validated with STAPLE algorithm. For each participating centre, the GS-PTV of each patient was created by applying the same margins as those used for the SC-CTV to SC-PTV expansion and replaced the SC-PTV in the treatment plan. Datasets were imported into MIM v6.1.7 [MIM Software Inc.], where dose-volume histograms (DVHs) were extracted and differences were analysed.17/18 centres used intensity-modulated RT (IMRT). The CTV to PTV margins ranged from 0 to 10 mm (median 5 mm). No correlation was observed between GS-CTV coverage by 95% isodose and GS-PTV margins width. Doses delivered to 98% (D98) and 95% (D95) of GS-CTVs were significantly lower than those delivered to the SC-CTVs. No significant difference between SC-CTV and GS-CTV was observed in maximum dose (D2), always under 110%. Mean dose ≥99% of the SC-CTVs and GS-CTVs was satisfied in 84% and 50%, respectively. In less than one half of plans, GS-CTV V95% was above 90%. Breaking down the GS-CTV into the three nodal levels (L2, L3 and L4), L4 had the lowest probability to be covered by the 95% isodose.Overall, GS-CTV resulted worse coverage, especially for L4. IMRT was largely used and CTV-to-PTV margins did not compensate for contouring issues. The results highlighted the need for delineation training and standardization.

Lombardy has represented the Italian and European epicenter of the coronavirus disease 2019 (COVID-19) pandemic. Although most clinical efforts within hospitals were diverted towards the care of virally infected patients, therapies for patients with cancer, including radiotherapy (RT), have continued. During both the first and second pandemic waves, several national and regional organizations provided Italian and Lombardian RT departments with detailed guidelines aimed at ensuring safe treatments during the pandemic. The spread of infection among patients and personnel was limited by adopting strict measures, including triage procedures, interpersonal distance, and adequate implementation of personal protective equipment (PPE). Screening procedures addressed to both the healthcare workforce and patients, such as periodic nasopharyngeal swabs, have allowed the early identification of asymptomatic or pauci-symptomatic COVID-19 cases, thus reducing the spread of the infection. Prevention of infection was deemed of paramount importance to protect both patients and personnel and to ensure the availability of a minimum number of staff members to maintain clinical activity. The choice of treating COVID-19–positive patients has represented a matter of debate, and the risk of oncologic progression has been weighted against the risk of infection of personnel and other patients. Such risk was minimized by creating dedicated paths, reserving time slots, applying intensified cleaning procedures, and supplying personnel and staff with appropriate PPE. Remote working of research staff, medical physicists, and, in some cases, radiation oncologists has prevented overcrowding of shared spaces, reducing infection spread.

Objectives: To determine interobserver variability in axillary nodal contouring in breast cancer (BC) radiotherapy (RT) by comparing the clinical target volume of participating single centres (SC-CTV) with a gold-standard CTV (GS-CTV). Methods: The GS-CTV of three patients (P1, P2, P3) with increasing complexity was created in DICOM format from the median contour of axillary CTVs drawn by BC experts, validated using the simultaneous truth and performance-level estimation and peer-reviewed. GS-CTVs were compared with the correspondent SC-CTVs drawn by radiation oncologists, using validated metrics and a total score (TS) integrating all of them. Results: Eighteen RT centres participated in the study. Comparative analyses revealed that, on average, the SC-CTVs were smaller than GS-CTV for P1 and P2 (by −29.25% and −27.83%, respectively) and larger for P3 (by +12.53%). The mean Jaccard index was greater for P1 and P2 compared to P3, but the overlap extent value was around 0.50 or less. Regarding nodal levels, L4 showed the highest concordance with the GS. In the intra-patient comparison, L2 and L3 achieved lower TS than L4. Nodal levels showed discrepancy with GS, which was not statistically significant for P1, and negligible for P2, while P3 had the worst agreement. DICE similarity coefficient did not exceed the minimum threshold for agreement of 0.70 in all the measurements. Conclusions: Substantial differences were observed between SC- and GS-CTV, especially for P3 with altered arm setup. L2 and L3 were the most critical levels. The study highlighted these key points to address. Advances in knowledge The present study compares, by means of validated geometric indexes, manual segmentations of axillary lymph nodes in breast cancer from different observers and different institutions made on radiotherapy planning CT images. Assessing such variability is of paramount importance, as geometric uncertainties might lead to incorrect dosimetry and compromise oncological outcome.

Simple Summary Concurrent chemo-radiotherapy is the standard treatment in anal cancer. Intensity-modulated radiotherapy (IMRT) was proved to reduce severe, acute and late toxicities. Moreover, IMRT techniques allow for the planning and delivery of a simultaneous integrated boost (SIB), with a differential dose per fraction given to selected sub-regions during the same treatment session. This boost modality provides the chance to employ a dose-painted approach with a reduction in overall treatment time that could result in a potential clinical advantage. Since a large variability in dose prescription to the primary tumor and elective or involved lymph nodes can be found in available guidelines and clinical practice, a multicenter analysis was conducted to evaluate the pattern of care and the impact of radiotherapy parameters on clinical outcomes for anal cancer patients treated with IMRT techniques within a national cohort. Abstract A multi-institutional retrospective study was conducted to evaluate the pattern of care and clinical outcomes of anal cancer patients treated with intensity-modulated radiotherapy (IMRT) techniques. In a cohort of 987 patients, the clinical complete response (CR) rate (beyond 6 months) was 90.6%. The 3-year local control (LC) rate was 85.8% (95% CI: 84.4–87.2), and the 3-year colostomy-free survival (CFS) rate was 77.9% (95% CI: 76.1–79.8). Three-year progression-free survival (PFS) and overall survival (OS) rates were 80.2% and 88.1% (95% CI: 78.8–89.4) (95% CI: 78.5–81.9), respectively. Histological grade 3 and nodal involvement were associated with lower CR (p = 0.030 and p = 0.004, respectively). A statistically significant association was found between advanced stage and nodal involvement, and LC, CFS, PFS, OS and event-free survival (EFS). Overall treatment time (OTT) ≥45 days showed a trend for a lower PFS (p = 0.050) and was significantly associated with lower EFS (p = 0.030) and histological grade 3 with a lower LC (p = 0.025). No statistically significant association was found between total dose, dose/fraction and/or boost modality and clinical outcomes. This analysis reports excellent clinical results and a mild toxicity profile, confirming IMRT techniques as standard of care for the curative treatment of anal cancer patients. Lymph node involvement and histological grade have been confirmed as the most important negative prognostic factors.

• Italy has been slowly reopening after a 10 week lockdown following COVID-19 outbreak. • A survey was administered to Italian RT departments to depict the current scenario. • In P1, RT departments managed to contain contagion with modest workload reduction. • All safety measures, maintained in P2, allowed RT departments to restore activities. • Reorganization of activities will be crucial to prevent the second wave of pandemic.

Background Italy experienced one of the world’s severest COVID-19 outbreak, with Lombardy being the most afflicted region. However, the imposed safety measures allowed to flatten the epidemic curve and hence to ease the restrictions and inaugurate, on the 4th of May 2020, the Italian phase (P) 2 of the pandemic. The present survey study, endorsed by CODRAL and AIRO-L, aimed to assess how radiotherapy (RT) departments in Lombardy have dealt with the recovery. Materials and methods A questionnaire dealing with the management of pandemic was developed online and sent to all CODRAL Directors on the 10th of June 2020. Answers were collected in full anonymity one week after. Results All the 33 contacted RT facilities (100%) responded to the survey. Despite the scale of the pandemic, during P1 14 (42.4%) centres managed to safely continue the activity (≤ 10% reduction). During P2, 10 (30.3%) centres fully recovered and 14 (42.4%) reported an increase. Nonetheless, 6 (18.2%) declared no changes and, interestingly, 3 (9.1%) reduced activities. Overall, 21 centres (63.6%) reported suspected or positive cases within healthcare workforce since the beginning of the pandemic. Staff units were quarantined in 19 (57.6%) and 6 (18.2%) centres throughout P1 and P2, respectively. In the two phases, about two thirds centres registered positive or suspected cases amongst patients. Conclusion The study revealed a particular attention to anti-contagion measures and a return to normal or even higher clinical workload in most RT centres in Lombardy, necessary to carry out current and previously deferred treatments. Electronic supplementary material The online version of this article (10.1007/s12032-020-01434-1) contains supplementary material, which is available to authorized users.

Introduction: Several efforts are being implemented at the European level to measure provision of up-to-date radiation treatments across the continent. Methods: A snapshot survey involving all radiation oncology centers within Lombardy, Italy, was performed in 2012 and repeated in 2014 and 2016, in cooperation with regional governmental officers. Centers were asked to provide detailed information concerning all individual patients being treated on the index day, and to report data on available local resources. Results: We observed an increase in the number of centers and of megavoltage units (MVU) (from 76 to 87, i.e., 8.7 MVU per million inhabitants in 2016). Mean number of MVU per center was 2.5. Average age of MVU increased from 5.3 to 7.5 years and patients on the waiting list also increased. Conformal 3D radiotherapy (RT) treatments decreased from 56% to 42% and were progressively replaced by intensity-modulated RT treatments (from 39% to 49%). Waiting times were overall satisfactory. Radiation oncologists treated on average 152 and radiation therapists 100 RT courses per year. Average reimbursement per course was €4,879 (range €2,476–€8,014). Conclusions: The methodology of snapshot survey proved feasible and provided valuable information about radiation oncology provision and accessibility in Lombardy.

Background The National Research Council (CNR) prostate cancer monitoring project in Italy (Pros-IT CNR) is an observational, prospective, ongoing, multicentre study aiming to monitor a sample of Italian males diagnosed as new cases of prostate cancer. The present study aims to present data on the quality of life at time prostate cancer is diagnosed. Methods One thousand seven hundred five patients were enrolled. Quality of life is evaluated at the time cancer was diagnosed and at subsequent assessments via the Italian version of the University of California Los Angeles-Prostate Cancer Index (UCLA-PCI) and the Short Form Health Survey (SF-12). Results At diagnosis, lower scores on the physical component of the SF-12 were associated to older ages, obesity and the presence of 3+ moderate/severe comorbidities. Lower scores on the mental component were associated to younger ages, the presence of 3+ moderate/severe comorbidities and a T-score higher than one. Urinary and bowel functions according to UCLA-PCI were generally good. Almost 5% of the sample reported using at least one safety pad daily to control urinary loss; less than 3% reported moderate/severe problems attributable to bowel functions, and sexual function was a moderate/severe problem for 26.7%. Diabetes, 3+ moderate/severe comorbidities, T2 or T3-T4 categories and a Gleason score of eight or more were significantly associated with lower sexual function scores at diagnosis. Conclusions Data collected by the Pros-IT CNR study have clarified the baseline status of newly diagnosed prostate cancer patients. A comprehensive assessment of quality of life will allow to objectively evaluate outcomes of different profile of care.

Aims: To evaluate the use of radiotherapy (RT) for oligometastatic cancer (OMC) among radiation oncologists in Lombardy, Italy. Methods and study design: A survey with 12 items regarding data of 2016 was sent to all 34 Lombardy RT centers. The survey included six general items and six specific items regarding patient/disease/treatment characteristics. Results: Thirteen centers answered the survey (38%). All centers responded to general items and 12 centers submitted patient/disease/treatment data. General items The majority of centers (8/13) consider OMC if metastases number is less than 5. The most commonly prescribed dose/fraction is 5–10Gy (8/13) using schedules of 3–5 fractions (11/13). Patient data items A total of 15.681 patients were treated in 2016 with external beam RT in 12 responding centers, and 1.087 patients were treated for OMC (7%). Primary tumor included lung, prostate, breast, colorectal and other malignancies in 33%, 21%, 12%, 9% and 25% of all OMC patients, respectively. Brain, lymph node, lung, bone, liver and others were the most common treated sites (24%, 24%, 22%, 17%, 8% and 5%, respectively). One and more than one metastasis were treated in 75 and 25% of patients, respectively. The vast majority of patients (95%) were treated with image-guided intensity-modulated RT or stereotactic RT. Conclusions: Seven percent of all RT patients in Lombardy are treated for OMC. Extreme hypofractionation and high-precision RT are commonly employed. The initiative of multicenter and multidisciplinary collaboration has been undertaken in order to prepare the platform for prospective and/or observational studies in OMC.

Aim of the study: The European Society of Breast Cancer Specialists (EUSOMA) has fostered a voluntary certification process for breast centres to establish minimum standards and ensure specialist multidisciplinary care. Prospectively collected anonymous information on primary breast cancer cases diagnosed and treated in the units is transferred annually to a central EUSOMA data warehouse for continuous monitoring of quality indicators (QIs) to improve quality of care. Units have to comply with the EUSOMA Breast Centre guidelines and are audited by peers. The database was started in 2006 and includes over 110,000 cancers from breast centres located in Germany, Switzerland, Belgium, Austria, The Netherlands, Spain, Portugal and Italy. The aim of the present study is assessing time trends of QIs in EUSOMA-certified breast centres over the decade 2006-2015. Materials and methods: Previously defined QIs were calculated for 22 EUSOMA-certified breast centres (46122 patients) during 2006-2015. Results: On the average of all units, the minimum standard of care was achieved in 8 of 13 main EUSOMA QIs in 2006 and in all in 2015. All QIs, except removal of at least 10 lymph nodes at axillary clearance and oestrogen receptor-negative tumours (T > 1 cm or N+) receiving adjuvant chemotherapy, improved significantly in this period. The desirable target was reached for two QIs in 2006 and for 7 of 13 QIs in 2015. Conclusion: The EUSOMA model of audit and monitoring QIs functions well in different European health systems and results in better performance of QIs over the last decade. QIs should be evaluated and adapted on a regular basis, as guidelines change over time. (C) 2017 Elsevier Ltd. All rights reserved.

Purpose To compare infrared (IR) optical vs. stereoscopic X-ray technologies for patient setup in image-guided stereotactic radiotherapy. Methods and Materials Retrospective data analysis of 233 fractions in 127 patients treated with hypofractionated stereotactic radiotherapy was performed. Patient setup at the linear accelerator was carried out by means of combined IR optical localization and stereoscopic X-ray image fusion in 6 degrees of freedom (6D). Data were analyzed to evaluate the geometric and dosimetric discrepancy between the two patient setup strategies. Results Differences between IR optical localization and 6D X-ray image fusion parameters were on average within the expected localization accuracy, as limited by CT image resolution (3 mm). A disagreement between the two systems below 1 mm in all directions was measured in patients treated for cranial tumors. In extracranial sites, larger discrepancies and higher variability were observed as a function of the initial patient alignment. The compensation of IR-detected rotational errors resulted in a significantly improved agreement with 6D X-ray image fusion. On the basis of the bony anatomy registrations, the measured differences were found not to be sensitive to patient breathing. The related dosimetric analysis showed that IR-based patient setup caused limited variations in three cases, with 7% maximum dose reduction in the clinical target volume and no dose increase in organs at risk. Conclusions In conclusion, patient setup driven by IR external surrogates localization in 6D featured comparable accuracy with respect to procedures based on stereoscopic X-ray imaging.

We report on 14 patients treated with linac- or robotic image-guided stereotactic radiotherapy for isolated lymph node recurrence from prostate cancer, up to the mean dose of 30 Gy/3 fractions. At the mean follow-up of 18.6 months, five patients experienced clinical out-field progression. Toxicity was minimal. Further investigation is warranted in order to identify the patients that benefit most from this treatment modality and to define the optimal association of such local approach with androgen deprivation. Hopefully, effective local therapy might reduce the burden of systemic therapies given to the recurrent/metastatic prostate cancer patients.

Background We have assessed the survival rate of patients with non–small cell lung cancer and synchronous hematogenous solitary metastasis identified with complete staging workup, including total body [ 18 F]fluorodeoxyglucose positron emission tomography scan, and treated with a multidisciplinary approach. Methods We examined the database of all patients who underwent surgery for primary non–small cell lung cancer in our institute. The criteria required for inclusion in this analysis were diagnosis of non–small cell lung cancer with synchronous hematogenous solitary metastasis by staging workup with total body computed tomography scan and brain magnetic resonance if indicated, total body positron emission tomography scan, radical surgery for the primary tumors, local treatment of the solitary metastasis, and systemic chemotherapy administration. Results We analyzed the data from 1,509 patients treated from January 2000 to December 2005: 10 patients (0.7%) satisfied the selection criteria. The median overall survival was 26 months, and the median time to progression was 20 months; 6 patients were alive at the time of analysis, with a median follow-up of 30 months. Four patients were tumor progression–free after 9, 18, 23, and 32 months from the start of their treatment. Conclusions The presentation of non–small cell lung cancer with a synchronous hematogenous solitary metastasis identified by [ 18 F]fluorodeoxyglucose positron emission tomography containing complete staging workup is extremely rare. This subset of patients can achieve long-term survival after a multidisciplinary treatment approach.

SummaryBackground and objective: Reducing postoperative mechanical ventilation in patients undergoing liver transplantation may have clinical and organizational advantages. On the basis of our experience, we here evaluate the possibility of practising immediate tracheal extubation in the operating theatre. Methods: In this prospective study, patients consecutively undergoing liver transplantation between 1 June 1999 and 31 May 2004 were extubated in the operating theatre at the end of surgery on the basis of standardized and universally accepted criteria, under conditions of haemodynamic and metabolic stability. Results: Two hundred and seven of the 354 patients (58.5%) were extubated immediately after the completion of the surgical procedure (mean time between end of surgery and extubation: 0.4 ± 1.4 min); two were re-intubated. In the last of the 5 yr of the study, the percentage of immediate extubations increased to 82.5%. During the study period, there was a progressive increase in the number of immediate extubations per individual member of the team of anaesthetists. The pre-transplant Child-Pugh severity of the underlying liver disease did not predict rapid extubation, but the Model for End-stage Liver Disease score of

Despite numerous randomized trials suggesting a benefit of unconventional fractionation in locally advanced head and neck cancer, the role of this approach in nasopharyngeal carcinoma is debatable. Based on the current clinical experience, the authors introduced hyperfractionated irradiation in the treatment of locally advanced head and neck cancer, including nasopharyngeal tumors. The preliminary results of this treatment approach in nasopharyngeal cancer patients are presented, with special focus on the pattern of failure and toxicity. 43 patients with nasopharyngeal cancer (stage II–IV, TNM 1997) underwent hyperfractionated irradiation. In 34 cases, radiotherapy was preceded by a median of three cycles of cisplatin-based induction chemotherapy. Irradiation was delivered using a shrinking-field technique up to a total dose of 74.4 Gy in 62 fractions of 1.2 Gy twice daily (minimum 6-h interval)/5 days/week. Acute toxicity of hyperfractionated radiotherapy was significant but tolerable. Mucositis proved the most common side effect (grade 3: 24 patients, grade 4: three patients). Severe late toxicity was not observed. 30 of 34 patients (88%) responded to induction chemotherapy. At 6 weeks after completion of radiotherapy, complete response was seen in 35 patients (81%), partial response in five (12%), stable disease in one, and progressive disease in two. After a median follow-up of 32 months, 18 patients (41%) developed progressive disease. Primary tumor progression was observed in three patients, and seven patients each showed regional lymph node progression and distant metastases. In one case both regional lymph node progression and distant metastases were diagnosed. The 2-year progression-free survival and overall survival rates were 58% and 84%, respectively. Hyperfractionated radiotherapy seems a feasible and active regimen in locally advanced nasopharyngeal carcinoma. Accompanying acute and late toxicity is acceptable and does not compromise delivery of the planned irradiation dose. This regimen is associated with a high local control rate; relatively high nodal and distant failure, however, call for further treatment modifications, e. g., optimization of irradiation technique and/or dose escalation as well as improved systemic therapies.

Aims and background Until recently radiotherapy of hepatic malignancies has played a limited role due to the well-known limited radiotolerance of the liver. The aim of this paper is to review the available data on the risk of radiation-induced liver disease (RILD) and to define the modern role of radiotherapy in the management of patients with metastatic or primary liver malignancies. Methods The advent of three-dimensional conformal treatment planning with dose-volume histogram analysis has made the study of partial liver irradiation possible. Limited portions of the liver may withstand high doses of radiation with minimal risk of RILD. Patients with solitary unresectable liver tumors may be treated with high-dose radiotherapy with curative intent. Recently, the feasibility of stereotactically guided treatment techniques with a single fraction or few treatment sessions has been explored in numerous institutions. Results The radiation tolerance of the whole liver found by several investigations is in the order of approximately 30 Gy, which seriously restricts its clinical application. The role of whole liver irradiation therefore appears of limited benefit in the palliation of patients with multiple liver metastases. The use of three-dimensional conformal techniques has made partial liver irradiation possible to doses in the 70–80 Gy range with conventional fractionation. At least two published series have reported improved local control and survival rates with dose escalation with three-dimensional conformal radiotherapy in patients with unresectable liver metastases. Similar outcomes have been recently reported with single dose (or hypofractionated) stereotactic radiotherapy both in metastatic and primary hepatic malignancies with minimal morbidity. Accurate target delineation and treatment reproducibility are the key to the success of this novel treatment approach, and specific treatment planning techniques and patient setup procedures must be developed to implement it. Conclusions Stereotactic high-dose radiotherapy is technically feasible for the treatment of inoperable liver malignancies, with the potential of high local control and low morbidity. Definitive evidence on the clinical advantages of this technique over other more established treatments can only be gathered from well-designed clinical studies.

Aiming to remove the toxins produced during the course of severe hepatic failure, we combined hemodiafiltration and plasma exchange (patient plasma replaced by fresh frozen plasma in a twice-daily regimen) for treatment of five patients: two affected by primary nonfunction of a liver graft and three by fulminant hepatic failure. The simultaneous use of the two extracorporeal techniques allowed a rapid reduction in the administration of vasoactive drugs and a rapid, significant decrease in the indices of liver necrosis. Native liver functional recovery occurred in one case, and the wait for a second graft was made possible in the other four. Although it has been reported that the detoxifying efficacy of plasma exchange is optimal when the replaced volume of plasma is high, such a technique requires both long treatment times and high blood flows in the extracorporeal circuit, making it often hemodynamically intolerable. Our approach leads to replacement of smaller volumes, allowing lower blood flows that are better tolerated despite the often unstable hemodynamics of these patients. Liver transplantation and retransplantation remains the definite therapy for severe liver failure or primary nonfunction. However, the organ waiting time is unpredictable and often does not coincide with the patients' clinical needs. Thus alternative strategies must be developed until a suitable donor is found or there is spontaneous recovery. From this point of view, in our albeit limited experience, twice-daily plasma exchange combined with hemodiafiltration has proved to be an effective therapeutic approach.

Background: the role of endovascular brachytherapy in restenosis prevention is well documented. Dose is usually prescribed at a fixed distance from the source axis by angiographic quantification of vessel diameter. Recently, intravascular ultrasound (IVUS) was introduced in dose prescription, allowing a better evaluation of the vessel anatomy. This study retrospectively explores the difference between prescription following angiographic vessel sizing and delivered dose calculated with IVUS. Methods and results: Seventeen lesions were studied with IVUS, identifying on irradiated segment, three sections on which measuring minimal and maximal distance from the centre of IVUS catheter to the adventitia; using dedicated software, corresponding doses were calculated. The dose ranged widely, with maximal and minimal values of 71.6 and 4.9 Gy; furthermore, heterogeneity in dose among different sections was observed. In the central section, the maximal dose was 206% of the one prescribed with the QCA model at 2 mm from the source axis, while the minimal dose was 96%. In proximal and distal sections, respective values were 182, 45, 243, and 122%. Conclusions: Our analysis confirmed the dose inhomogeneity delivered with an angiographic fixed-dose prescription strategy. A dose variation was found along the irradiated segment due to the differences in vessel thickness. IVUS emerged as an important tool in endovascular brachytherapy, especially for irregular-shaped vessels.

Aim of the study: The European Society of Breast Cancer Specialists (EUSOMA) has fostered a voluntary certification process for breast units to establish minimum standards and ensure specialist multidisciplinary care. In the present study we assess the impact of EUSOMA certification for all breast units for which sufficient information was available before and after certification. Materials and methods: For 22 EUSOMA certified breast units data of 30,444 patients could be extracted from the EUSOMA database on the evolution of QI's before and after certification. Results: On the average of all units, the minimum standard of care was achieved for 12/13 QI's before and after EUSOMA certification (not met for DCIS receiving just one operation). There was a significant improvement of 5 QI's after certification. The proportion of patients with invasive cancer undergoing an axillary clearance containing >9 lymph nodes (91.5% vs 89.4%, p 0.003) and patients with invasive cancer having just 1 operation (83.1% vs 80.4%, p < 0.001) dropped, but remained above the minimum standard. The targeted standard of breast care was reached for the same 4/13 QI's before and after EUSOMA certification. Conclusion: Although the absolute effect of EUSOMA certification was modest it further increases standards of care and should be regarded as part of a process aiming for excellence. Dedicated units already provide a high level of care before certification, but continuous monitoring and audit remains of paramount importance as complete adherence to guidelines is difficult to achieve. (C) 2015 Elsevier Ltd. All rights reserved.

Breast cancer rarely occurs in young women. Our knowledge about disease presentation, prognosis and treatment effects are largely dependent upon older series.We evaluated biological features and stage at presentation for 1427 consecutive premenopausal patients agedor = 50 years with first diagnosis of invasive breast cancer referred to surgery at the European Institute of Oncology from April 1997 to August 2000. A total of 185 patients (13%) were aged35 years ('very young') and 1242 (87%) were aged 35-50 years ('less young'). The expression of estrogen receptors (ER), progesterone receptors (PgR), presence of vascular invasion (VI), grading (G), expression of Ki-67, HER2/neu overexpression, pathological stage according to TNM staging system (pTNM), pathological tumor size and number of axillary lymph node involvement were evaluated.Compared with less young patients, the very young patient group had a higher percentage of tumors classified as ER negative (P0.001), PgR negative (P = 0.001), higher expression of Ki-67or = 20% of cells stained; 62.2% versus 53%, (P0.001), vascular or lymphatic invasion (48.6% versus 37.3%, P = 0.006), and pathological grade 3 (P0.0001). There was no difference between the two groups for pT, pathological tumor size (pN) and number of positive lymph nodes.We conclude that compared with less young premenopausal patients, very young women have a greater chance of having an endocrine-unresponsive tumor, and are more likely to present with a higher grade, more extensively proliferating and vessel invading disease. Pathological tumor size, nodal status and number of positive axillary lymph-nodes have a similar distribution among the younger and the older cohorts, thus not supporting previous data indicating more advanced disease in younger patients at diagnosis of operable disease.

Objective: We undertook a prospective phase II study to assess the feasibility and activity of a new induction chemotherapy regimen followed by hyperfractionated irradiation in locally advanced squamous cell head and neck cancer. Methods: 25 patients with locally advanced head and neck cancer were treated with 4 cycles of vinorelbine (20 mg i.v. day 1, 3), cisplatin (60 mg/m2 i.v. day 1) and 5-fluorouracil (200 mg/m2 continuous i.v. infusion day 1–21) (ViFuP regimen) followed by bifractionated radiotherapy (bidRT) up to 74.4 Gy in 62 fractions of 1.2 Gy twice daily. Results: Chemotherapy was well tolerated, 6 patients developed grade 3 and one patient grade 4 neutropenia. Response to chemotherapy was observed in 19 patients (76%) including three complete responses and 16 partial responses. Planned bidRT was completed in 25 patients and all but one received planned bidRT dose without interruptions. Radiotherapy was well tolerated, mucositis was the most common side effect (grade 3–12 patients, grade 4–1 patient). At evaluation after the completion of bidRT, 13 patients had complete response (52%), 7 partial response (28%), 2 stable disease and 3 tumor progression. At the median follow-up of 18.2 months, 11 patients were alive and free of disease, and 14 patients had died (12 of tumor). Late xerostomy was observed in all but one 3-month survivors. Late mandibular necrosis was seen in 1 patient. Conclusions: bidRT preceded by ViFuP seems a feasible and active combination in locally advanced head and neck cancer. Good patient compliance did not compromise the delivery of planned dose of bidRT. However, short median duration of response (14.6 months) and moderate median overall survival (18.7 months) indicate the need for more intensive therapeutic strategies. On the basis of these results, modifications of our treatment schedule (shortening the overall treatment time by reduction of chemotherapy cycles and the use of chemotherapy concomitantly with irradiation) are planned for the future study.

Aims and Background Bladder preservation is a treatment option in muscle-invasive bladder carcinoma. The most investigated approach is a trimodality schedule including maximum transurethral resection of bladder tumor (TURBT) followed by chemoradiotherapy. Our aim was to evaluate the use of bladder preservation by radiation oncologists of the Lombardy region in Italy. Methods and Study Design A survey with 13 items regarding data of 2012 was sent to all 32 radiotherapy centers within the collaboration between the Lombardy Oncological Network and the Lombardy Section of the Italian Society of Oncological Radiotherapy. Results Thirteen centers (41%) answered the survey; the presented data come from 11 active centers. In these centers, 11,748 patients were treated with external-beam radiotherapy in 2012, 100 of whom having bladder cancer (0.9%). 74/100 patients received radiotherapy as palliative treatment for T, N or M lesions. A further 9 and 5 patients received radiotherapy for oligometastatic disease (ablative doses to small volumes) and postoperatively, respectively. Bladder preservation was performed in 12 cases and included trimodality and other strategies (mainly TURBT followed by radiotherapy). A multidisciplinary urology tumor board met regularly in 5 of 11 centers. All responders declared their interest in the Lombardy multicenter collaboration on bladder preservation. Conclusions Our survey showed that bladder preservation is rarely used in Lombardy despite the availability of the latest radiotherapy technologies and the presence of an urology tumor board in half of the centers. The initiative of multicenter and multidisciplinary collaboration was undertaken to prepare the platform for bladder preservation as a treatment option in selected patients.

(2009). Breakthrough Fusarium spp Fungemia During Caspofungin Therapy in an ABO-Incompatible Orthotopic Liver Transplant Patient. Journal of Chemotherapy: Vol. 21, No. 2, pp. 236-238.

Background Parvus-tardus waveforms of the hepatic artery after liver transplantation usually indicate an arterial complication and severe impairment of hepatic arterial perfusion with a sensitivity of 91% and a specificity of 99.1%. Thus, it has been emphasized that detection of such waveforms should prompt emergency angiography. Materials and Methods Arterial reconstruction during a liver transplantation was successfully accomplished by an end-to-end anastomosis, performing a “flute-spout” widening of the anastomosis with a 7/0 prolene running suture between a small recipient proper hepatic artery and the donor common hepatic artery. Results On day 7 posttransplantation color Doppler ultrasonography revealed a parvus-tardus waveform pattern in the hepatic arterial flow. Computed tomographic (CT) angiography showed only a caliber discrepancy between the donor and recipient stumps, excluding an arterial stenosis or thrombosis. Since normal liver function persisted, the patient underwent routine follow-up. After 15 months the patient was alive and well; hepatic artery spectral waveforms were unchanged and liver functions were consistent with a mild hepatitis C virus (HCV) recurrence. Conclusions This is a report of false positive tardus-parvus waveforms, due to a discrepancy between the donor and recipient arteries despite a wide anastomosis. Knowledge of technical reconstruction details may be helpful for correct interpretation of color Doppler findings. CT angiography should be considered before more invasive examinations.

Background Originally introduced for cutaneous T-cell lymphomas and autoimmune diseases, extracorporeal photopheresis (ECP) has been proven effective to reverse allograft rejection. The aim of the present work was to show the results of a single-center experience with ECP for the treatment of biopsy-proven rejection in selected liver transplant (LT) recipients. Patients and methods A retrospective review of five LT patients (M:F = 4:1; median age 51 years) undergoing ECP for biopsy-proven allograft rejection between January 1996 and December 2003. In this period 476 LT were performed on 441 patients. Results The indications for LT were three cases of HCV-related cirrhosis, complicated by hepatocellular carcinoma in two; one HBV-HDV-alcoholic cirrhosis; and one fulminant HBV hepatitis. All patients received calcineurin-inhibitor (CNI)-based immunosuppression with induction using anti-IL2R monoclonal antibodies. Indications for ECP were: ductopenic rejection in one patient with HCV recurrence; steroid-resistant acute rejection in two; acute rejection in a major ABO-mismatched liver graft; and one acute rejection in a patient with a proven allergy to steroids. The median interval from LT to inception of ECP was 43 days. The median number of ECP sessions per patient was 20. During the course of ECP, two patients tested positive for CMV antigenemia, associated in one case with bacterial pneumonia. All patients tolerated ECP and there were no procedure-related complications. At a median follow-up of 7.9 months after start of ECP, neither rejection relapses nor HCV/HBV recurrences have been observed. Three patients are off ECP with complete reversal and low-dose immunosuppression. Two patients are still receiving ECP with full-dose immunosuppression: one has achieved normal liver function but ECP is indicated due to a major ABO-incompatible liver graft, while the other patient's liver functions have not yet returned to baseline values.

A joint analysis of clinical data from centres within the European section of the International Society of Intraoperative Radiation Therapy (ISIORT-Europe) was undertaken in order to define the range of intraoperative radiotherapy (IORT) techniques and indications encompassed by its member institutions. In 2007, the ISIORT-Europe centres were invited to record demographic, clinical and technical data relating to their IORT procedures in a joint online database. Retrospective data entry was possible. The survey encompassed 21 centres and data from 3754 IORT procedures performed between 1992 and 2011. The average annual number of patients treated per institution was 42, with three centres treating more than 100 patients per year. The most frequent tumour was breast cancer with 2395 cases (63.8 %), followed by rectal cancer (598 cases, 15.9 %), sarcoma (221 cases, 5.9 %), prostate cancer (108 cases, 2.9 %) and pancreatic cancer (80 cases, 2.1 %). Clinical details and IORT technical data from these five tumour types are reported. This is the first report on a large cohort of patients treated with IORT in Europe. It gives a picture of patient selection methods and treatment modalities, with emphasis on the main tumour types that are typically treated by this technique and may benefit from it.

OBJECTIVES: To evaluate stereotactic body radiotherapy (SBRT) for single abdominal lymph node cancer recurrence. METHODS: Inclusion criteria for this retrospective study were as follows: adult oligometastatic cancer patients with single abdominal lymph node recurrence that underwent SBRT but not other local therapy, written informed consent for treatment. Previous radiotherapy or concomitant systemic therapy were allowed. Toxicity and tumor response were evaluated using Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Scale and Response Evaluation Criteria in Solid Tumors. RESULTS: Sixty-nine patients (94 lesions) underwent SBRT (median 24 Gy/3 fractions). Primary diagnosis included urological, gastrointestinal, gynecologic, and other malignancies. Concomitant systemic therapy was performed in 35 cases. Median follow-up was 20 months. Two grade 3 acute and 1 grade 4 late toxicity events were registered. Complete radiologic response, partial response, stabilization, and progressive disease were observed in 36 (44%), 21 (26%), 20 (25%), and 4 (5%) lesions, respectively, out of 81 evaluable lesions. Response rates were similar when analysis was restricted to lesions treated with exclusive SBRT (no concomitant therapy). Actuarial 3-year in-field progression-free interval, progression-free survival and overall-survival rates were 64.3%, 11.7%, and 49.9%, respectively. Overall-survival rates were significantly higher in favorable histology cases (prostate and kidney tumors). Pattern of failure was predominantly out-field. CONCLUSIONS: SBRT is a feasible approach for single abdominal lymph node recurrence, offering excellent in-field tumor control with low-toxicity profile. Future studies are warranted to identify the patients that benefit most from this treatment. The optimal combination with systemic treatment should also be defined.

The purpose of this work was to evaluate the intrapatient tumor position reproducibility in a deep inspiration breath‐hold (DIBH) technique based on two infrared optical tracking systems, ExacTrac and ELITETM, in stereotactic treatment of lung and liver lesions. After a feasibility study, the technique was applied to 15 patients. Each patient, provided with a real‐time visual feedback of external optical marker displacements, underwent a full DIBH, a free‐breathing (FB), and three consecutive DIBH CT‐scans centered on the lesion to evaluate the tumor position reproducibility. The mean reproducibility of tumor position during repeated DIBH was 0.5±0.3mm in laterolateral (LL), 1.0±0.9mm in anteroposterior (AP), and 1.4±0.9mm in craniocaudal (CC) direction for lung lesions, and 1.0±0.6mm in LL, 1.1±0.5mm in AP, and 1.2±0.4mm in CC direction for liver lesions. Intra‐and interbreath‐hold reproducibility during treatment, as determined by optical markers displacements, was below 1 mm and 3 mm, respectively, in all directions for all patients. Optically‐guided DIBH technique provides a simple noninvasive method to minimize breathing motion for collaborative patients. For each patient, it is important to ensure that the tumor position is reproducible with respect to the external markers configuration. PACS numbers: 87.53.Ly, 87.55.km

This paper describes an uncommon radiation treatment of the external ear, with ultrasound (US) transmission gel used as bolus device to compensate for the irregularity of the target surface.Postoperative radiotherapy for cutaneous carcinoma was performed with a single high-energy electron beam directed over the ear auricle. Due to the irregular surface of the target, a "missing tissue" compensator was employed. Daily, after patient positioning, the concha was filled and flattened with US gel, and a dose of 54 Gy in 27 fractions was delivered.Water equivalence of the gel was verified by comparing the gel's computed tomography (CT) number [Hounsfield units (HU)] and density with the corresponding values for water and another commercial bolus device. Whereas ultrasound gel and water had comparable values (HU: 0; density 1 g/cm(3) for both), the corresponding values for the commercial device were slightly higher (HU: 80; density 1.02 g/cm(3)).Ultrasound gel proved to be an easy, fast and cheap compensating tool. Its water equivalence allows it to be used as an alternative to water, though easier to position and with lower risk of displacement. Thus, it is recommendable as a practical tool for most irregular sites. Further investigations are warranted to validate this solution in more complex irradiation techniques.

A prospective study for stage IIIA-B nonsmall cell lung cancer (NSCLC), with three-times daily (3td) radiotherapy (RT), after induction chemotherapy (iCT), with or without surgery.Induction cisplatin and gemcitabine chemotherapy was delivered. Surgery and postoperative (post-op) radiotherapy were planned for responsive stage IIIA patients; definitive irradiation was performed in unresectable IIIA and IIIB patients. Doses of 54.4 and 64.6 Gy were delivered for the post-op and definitive treatments, respectively.Out of 52 patients (pts), 37 received 3tdRT as definitive (18 pts) or post-op treatment (19 pts). Overall, the failures were similar between post-op and definitive 3tdRT (78.9% vs. 77.8%). In the post-op treatment, metastases and local failures were 52.6% and 10.5%, respectively and in the definitive radiotherapy, the incidence was similar (local 33.3% vs. systemic 44.4%). The five-year overall survival (OS) was 25% for the post-op and 21% for the definitive patients (p = 0.87).Three-times daily postoperative radiotherapy did not improve the outcome in NSCLC, but for unresectable patients, this approach may have a role in selected cases.

Merkel cell carcinoma (MCC) is an uncommon aggressive neuroendocrine skin carcinoma. It usually affects sun-exposed skin of white elderly people. MCC is characterized by a high incidence of early locoregional relapse and distant metastases. Because of its rarity and the resulting lack of prospective randomized trials, data regarding the optimal treatment of MCC are limited. Despite aggressive multimodality treatment, the prognosis of patients bearing MCC is often poor. We report three cases of lymph node metastases of MCC with unknown primary sites. Two patients died 17 and 28 months after diagnosis due to brain and pancreatic metastases, respectively, without evidence of cutaneous disease. The third patient is alive and free of tumor at 16 months from the diagnosis. After an accurate diagnosis of lymph node metastases from MCC, the absence of a primary tumor at complete initial evaluation and during adequate follow-up can confirm this particular clinical scenario. The prognosis seems to be analogous to that of cases with similar disease stage (lymph node involvement) but a known primary site.

Acute hepatic failure (ALF) is an uncommon disease characterized by a rapid deterioration of the hepatic function with severe derangements of the mental status in previously healthy subjects due to massive hepatocytes necrosis. Neurological impairment, due to intracranial hypertension and cerebral ischemia, is a key factor because it is a main criterion to decide when to proceed to liver transplantation, which is only treatment for these patients. Therefore, neurological monitoring holds an essential role in the clinical management of ALF patients but it needs to be performed at the point-of-care in the majority of the cases as such critically ill patients cannot be moved away from the ICU because they frequently need continuous hemodynamic, ventilatory and renal support. We herein report and discuss our experience relating to the use of transcranial sonography as a neuro-monitoring tool in ALF patients. In our series this technique allowed a repeatable and reliable non-invasive assessment of cerebral blood flow changes at the bedside thus avoiding the complications associated with the use of an intracranial probe to measure intra-cranial pressure and making it possible to correctly evaluate the timing and feasibility of liver transplantation.

To quantify the advantages of a 6 degrees of freedom (dof) versus the conventional 3- or 4-dof correction modality for stereotactic body radiation therapy (SBRT) treatments. Eighty-five patients were fitted with 5-7 infra-red passive markers for optical localization. Data, acquired during the treatment, were analyzed retrospectively to simulate and evaluate the best approach for correcting patient misalignments. After the implementation of each correction, the new position of the target (tumor's center of mass) was estimated by means of a dedicated stereotactic algorithm. The Euclidean distance between the corrected and the planned location of target point was calculated and compared to the initial mismatching. Initial and after correction median+/-quartile displacements affecting external control points were 3.74+/-2.55 mm (initial), 2.45+/-0.91 mm (3-dof), 2.37+/-0.95 mm (4-dof), and 2.03+/-1.47 mm (6-dof). The benefit of a six-parameter adjustment was particularly evident when evaluating the results relative to the target position before and after the re-alignment. In this context, the Euclidean distance between the planned and the current target point turned to 0.82+/-1.12 mm (median+/-quartile values) after the roto-translation versus the initial displacement of 2.98+/-2.32 mm. No statistical improvements were found after 3- and 4-dof correction (2.73+/-1.22 mm and 2.60+/-1.31 mm, respectively). Angular errors were 0.09+/-0.93 degrees (mean+/-std). Pitch rotation in abdomen site showed the most relevant deviation, being -0.46+/-1.27 degrees with a peak value of 5.46 degrees . Translational misalignments were -0.68+/-2.60 mm (mean+/-std) with the maximum value of 12 mm along the cranio-caudal direction. We conclude that positioning system platforms featuring 6-dof are preferred for high precision radiation therapy. Data are in line with previous results relative to other sites and represent a relevant record in the framework of SBRT.

Background: An institutional task force on upper gastrointestinal tumours is active at the European Institute of Oncology (EIO). Members decided to collate the institutional guidelines on management of liver tumours (primary and metastatic) into a document. This article is aimed at presenting the current treatment guidelines as well as ongoing research protocols and trials in this field at the EIO. Methods: A steering committee convened to assign tasks to individual members. Contributions from experts in each treatment area were collated in a single document, in order to produce a draft for subsequent review from the aforementioned committee. Six drafts have been discussed and the final version approved. Results: Surgical, medical oncology, interventional radiology, nuclear medicine and radiation therapy approaches, their roles in management of liver tumours and ongoing research trials are presented and discussed in this article. Conclusions: At the EIO a multi-disciplinary integrated approach to liver tumours is standard and several ongoing research projects are currently active in this field.

http://hdl.handle.net/20.500.11768/96592

We report the results of a prospective, intent-to-treat (ITT) trial on the costs of selective tumor downsizing (DS) before liver transplantation (LT) for patients affected with hepatocellular carcinoma (HCC). The trial started in January 1997 including adult patients with nodular-type HCC within and beyond the Milan criteria. Patients were downsized with transarterial chemoembolization (TACE), percutaneous ethanol injection (PEI) and/or radiofrequency ablation (RFA) according to clinical predictors. TACE and RFA were performed as inpatient procedures, while PEI was performed on an outpatient basis. Costs of DS were obtained according to the Tuscany Health Reimbursement Fee Catalog adjusted to yearly inflation rates from 1997 through 2005. Data analysis was performed at 1 year after the last enrollment of 198 patients, including 161 (81.3%) who were transplanted: 34 (17.2%) dropped out and 3 (1.5%) were still on the waiting list. One hundred and fifty-two patients (76.7%) underwent DS for a total of 201 procedures: 159 TACE, 39 PEI, and 3 RFA. Overall costs in Euros (euro) of waitlisting were 861,801.24 euro: 548,460 euro (63.7%) for pretransplantation evaluation; 197,994.84 euro (22.9%) for control visits and hospitalizations; and 115.346.4 euro (13.4%) for DS. Mean costs of DS were 758.58 euro +/- 270 euro per downstaged patient (747.53 euro +/- 257.1 euro Milan; 774.01 euro +/- 287.71 euro non-Milan); 582.85 euro +/- 398.87 euro per waitlisted patient (520.28 euro +/- 406.23 euro Milan; 520.28 +/- 364.48 euro non-Milan); and 716.4 euro per transplanted patient (580.67 euro Milan; 1026.76 euro non-Milan; +76.8%). A selective policy of tumor DS increased the costs of LT waitlisting by 13.4%, but due to higher dropout rates among non-Milan patients, the cost utility of DS was 76.8% higher in the Milan group.

Purpose: To investigate size and frequency of interfractional patient setup variability in hypofractionated stereotactic extracranial radiotherapy. Methods and Materials: Infrared optical 3D tracking of surface markers was applied to quantify setup variability on 51 patients. Isocenter position repeatability was assessed by means of frameless anatomic calibration and was compared with portal image evaluation. Specific data analysis allowed for compensation of patients' breathing movements and for separation of the effects of operator-dependent misalignments and respiration-induced displacements. Effects of patient position (supine vs. prone) and treatment table configuration were investigated. Results: Patient positioning assisted by the optical tracking device allowed reducing displacements of surface control points within the 3-mm range. Errors in isocenter localization were in the range of a few millimeters. This was in agreement with the portal image evaluation. Breathing motion introduced appreciable errors, which increased control points and isocenter 3D variability. This effect was significantly higher than those related to other investigated factors. Conclusions: The role of infrared optical tracking devices for patient positioning is assessed on a large patient population. Their use in the frame of high-precision radiotherapy is emphasized by the application of related methodologies for breathing phase detection and frameless isocenter localization.

Purpose To determine whether epidermal growth factor receptor (EGFR) expression in non–small-cell lung cancer (NSCLC) is modulated by chemotherapy and to assess the agreement of EGFR status between mediastinal nodes and the primary tumor after chemotherapy. Patients and Methods Patients with NSCLC stage IIIa/b pN2/3 confirmed by mediastinoscopy or mediastinostomy were treated with at least three cycles of chemotherapy before undergoing surgery. EGFR expression was evaluated on mediastinal nodes at the time of initial diagnosis and on both the primary tumor and residual metastatic nodes after treatment. Results EGFR expression determined on 138 of 164 patients who underwent mediastinoscopy or mediastinostomy was 0 (22 patients), 1+ (27 patients), 2+ (28 patients), and 3+ (61 patients). Fifty-four patients of 164 received chemotherapy followed by surgery. Of the 89 of 138 patients with EGFR score of 2+/3+ at the time of diagnosis, 34 patients underwent surgery after induction chemotherapy. None changed to zero EGFR immunoreactivity, with 29 patients (88%) maintaining a score of 2+/3+. Of the 22 of 138 patients with no EGFR expression at the time of diagnosis, six underwent surgical resection after induction chemotherapy. Of these six patients, four changed their EGFR expression from an EGFR score of 0 to 2+/3+. After treatment, the agreement of EGFR status between tumor and nodes in the subgroup of patients with EGFR score 2+/3+ was 89% to 92%. Conclusion Our data suggest a very good agreement of EGFR status before and after chemotherapy in EGFR-positive NSCLC. Induction chemotherapy can induce EGFR expression in occasional EGFR-negative tumors.

Aim of this study was to define the optimal schedule of gemcitabine (GCB)\cisplatin (CDDP) combination as induction chemotherapy (CHT) in patients with stage IIIa pN2-IIIb non - small-cell lung cancer (NSCLC). Fifty patients with mediastinoscopically-proven stage-IIIa pN2 -IIIb NSCLC were treated with 3 cycles of induction CHT followed by surgery (if staged IIIa) and three-time-daily accelerated radiotherapy. Chemotherapy initially consisted of 3 courses of CDDP 100 mg\m(2) d1 plus GCB 1000 mg\m(2) dd 1,8,15 repeated every 4 weeks, than was modified in CDDP 80 mg\m(2) d1 plus GCB 1250 mg\m(2) dd 1,8 repeated every 3 weeks. Twenty-nine four-week scheduled treatment cycles were firstly administered to 10 patients (pts): treatment-related toxicity, mainly hematological, caused a dose-reduction or treatment omission on day 15 in 65% of cycles. After the protocol was amended, 119 three-week scheduled treatment cycles were administered to 40 pts. Treatment-related toxicity of the new schedule caused a dose-reduction or treatment omission in only 10% of cycles, no patients requiring chemotherapy discontinuation. Thirty-seven out of fifty patients (74%, 95% CI: 60-85%) achieved a partial response, 7 had stable disease and 6 had disease progression. Similar activity was seen with both schedules. One nodal pathological complete remission was observed among the 24 pts who underwent surgery. At present, with a median follow-up of 13 months (mos), 2-year (y) survival of all the 50 pts and of the 24 pts staged IIIa who underwent surgery is estimated as 37% (95% CI: 24-58%) and 47% (95%CI: 27-80%), respectively. When given as induction chemotherapy, a three-week schedule of CDDP plus GCB combination appeared to be effective, with lower toxicity and better compliance than a four-week schedule.

To evaluate the feasibility and toxicity of three-times-daily radiotherapy (3tdRT), preceded by induction chemotherapy (iCT), in stage IIIA–IIIB non-small cell lung cancer (NSCLC). iCT consisted of three cycles of cisplatin and gemcitabine. Surgery was considered for stage IIIA patients responsive to iCT; definitive or postoperative 3tdRT was planned. Doses of 54.4 Gy and 64.6 Gy in postoperative and definitive treatments, respectively, were delivered in three daily fractions. From February 1998 to October 2000, 37 patients received 3tdRT as definitive (n = 18) or postoperative treatment (n = 19). Toxicity was limited to RTOG grade 2 (25 patients, 67.6%) and grade 3 (four patients, 10.8%) acute esophagitis; no grade 3 late esophagitis occurred. Late lung toxicity was represented by one grade 3 pneumonitis. No correlation emerged between acute esophageal toxicity and irradiated esophageal volume or disease- and treatment-related factors. A significant correlation was found for stage (IIIA vs. IIIB; p = 0.03) and a trend for the N-class (N2 vs. N3; p = 0.08). In this experience of 3tdRT preceded by iCT, the low toxicity profile confirmed the feasibility of this combination. The limited statistical power does not permit a definition of predictors for radiation-induced esophagitis incidence and severity; additional studies are required to clarify the impact of volumetric and dosimetric parameters. Failure patterns and survival results are warranted to confirm the efficacy of this approach in locally advanced NSCLC.

Background Extended pneumonectomy with partial resection of the left atrium for lung cancer is not frequently performed; therefore, its results remain controversial. The present study analyzed a single center's experience with this extended surgery, highlighting the surgery's technical aspects, postoperative outcomes, and oncologic results. Methods From November 1996 to December 2003, 15 patients underwent extended pneumonectomy with partial resection of the left atrium for lung cancer, without cardiopulmonary bypass. Results Of the 15 patients (median age of 63 years, range 35 to 74 years), 11 were men (73%) and 4 were women. Six patients (40%) underwent preoperative invasive mediastinal staging. Nine patients (60%) underwent induction chemotherapy. Nine patients (60%) underwent right pneumonectomy. Pathologic analysis of the specimens identified 8 patients (53%) with N2 disease, 5 patients (33%) with N1 disease, and 2 patients with N0 disease. The T status was T4 in 10 patients, pT3 in 3 patients, and T0 in the remaining 2 patients. The were 10 squamous cell carcinomas (60%), 2 adenocarcinomas, 1 adenosquamous carcinoma, 1 mucoepidermoid carcinoma, and 1 atypical carcinoid tumor. The median intensive care unit and hospital stay were 1 day and 6.4 days, respectively. There were only two (15.3%) minor postoperative complications (atrial arrhythmias), which were successfully treated medically. There was no postoperative mortality. At completion of the study, 9 patients (60%) were still alive, with 8 showing no evidence of disease. The remaining 6 patients died because of systemic recurrences. The 3-year probability of survival was 39%. Conclusions Extended pneumonectomy with partial resection of the left atrium for advanced lung cancer is a feasible procedure, with low postoperative morbidity and mortality. In fact, it can lead to excellent local control of the disease, if not to a permanent cure in select patients.

Background. The incidence and clinical relevance of increased intraabdominal pressure after orthotopic liver transplantation (OLT) has not yet been evaluated despite the finding that occurrence of this condition in postsurgical critically ill patients may impair various organ functions. The aim of this study was to assess whether the occurrence of abdominal hypertension among a population of OLT recipients was an important cofactor producing early postoperative complications. Method. This prospective clinical study measured abdominal pressure every 6 hours during the intensive care unit (ICU) stay using the urinary bladder method. A value of ≥25 mm Hg was considered high. Hemodynamic status was simultaneously evaluated and renal function assessed based on the hourly urinary output, and by calculating serum creatinine on postoperative days 2 and 4. Renal failure was defined as a serum creatinine level of >1.5 mg/dL, or an increase in peak of >1 mg/L within 72 hours of surgery. The filtration gradient and patient outcomes were also considered. Results. Intraabdominal hypertension was observed in 32% of cases. The subjects displaying high IAP showed significantly lower artery pressure values (P

Purpose To investigate the effects of interfraction setup uncertainties on the dose distribution within the clinical target volume (CTV) and the organs at risk (OAR) of left-sided breast cancer patients undergoing external radiotherapy. Methods and materials Interfractional setup errors were assessed by measuring surface control points displacements during 89 irradiation sessions in 4 patients, by means of opto-electronic localization. The measured position deviations were fed back to the treatment planning system for the evaluation of the corresponding dosimetric effects within CTV and OARs (lung, heart). Results Results revealed errors above 5 mm on some of the control points, but corresponding volumetric variations were on average below 2% for both the CTV within the 95–105% dose range and the OARs receiving more than 50% and 90% of the prescribed dose. A specific sensitivity to the setup errors was found as a function of the treatment plan design, leading to isolated cases exhibiting volumetric variations of CTV and OARs exceeding 2%. Conclusions This study confirms the potential increase of treatment quality provided by the systematic patient position verification and highlights the role of opto-electronic position detection systems for the real-time check of patient setup errors and the evaluation of the corresponding dosimetric consequences, as a way to achieve consistent dose delivery.

Intracoronary brachytherapy has significantly reduced the recurrence of in-stent restenosis. The aim of this study was to evaluate the feasibility, safety and efficacy of intracoronary beta-radiation in patients at very high risk for recurrence of in-stent restenosis.We analyzed 42 patients with 50 lesions submitted to catheter-based beta-radiation (Beta-Cath System, Novoste Corporation, Norcross, GA, USA) for in-stent restenosis. Thirty-eight lesions were at the second restenosis, 8 at the third, and 4 at the fourth; a diffuse pattern was present in 78%.Balloon angioplasty was performed for 30 lesions (60%) and the cutting balloon technique for 20 (40%). In 12 lesions further 14 stents had to be deployed (28%). The delivery catheter was successfully positioned in 96% of the procedures. The mean dwell time was 179 +/- 50 s with a radiation dose ranging from 18.4 to 25.3 Gy, depending on the vessel size. A complete angiographic success without coronary dissection and without any additional stenting after radiation delivery was achieved in 86%. At follow-up (7.2 +/- 2.1 months), the overall restenosis rate was 30.4% (14 lesions). A recurrence was detected in 1/11 lesions with initial focal pattern and in 13/39 lesions with initial diffuse pattern. The restenosis rate was higher in patients in whom a geographic miss had occurred (p0.05 vs lesions without geographic miss) and in those in whom a new stent had been deployed (p0.05 vs lesions treated without a stent).Brachytherapy reduces the in-stent restenosis rate in patients who are at very high risk of recurrence. The restenosis pattern, geographic miss and new stent deployment seem to be negative prognostic factors for recurrence of restenosis.

Background and purpose : The relationship between the radiation dose and the risk of the osteoradionecrosis is well known. However, the dose to the mandible is not routinely assessed in the radiotherapy for head and neck cancer. The aim of our study was to analyze the mandibular dose distribution in the patients administered curative radiotherapy for squamous cell carcinoma of the oropharynx. Moreover, the clinical results have been analyzed. Material and methods : We examined the clinical records and treatment plans in 18 patients treated with bifractionated radiotherapy for stage II–IV oropharyngeal cancer. In 17 patients, the total radiotherapy dose prescribed in the International Committee of Radiation Units and Measurements (ICRU) reference point was 74.4Gy administered in 62 fractions (1.2Gy twice daily with 6h interfraction interval) and one patient received a dose of 75.6Gy. The whole dose to the mandibular–orophryngeal region was delivered with 6MV photons. The mandible was contoured manually on computed tomographic scans and the point doses at the both mandibular condyles, ascending ramus, mental symphysis, molar and retromolar regions were assessed. Moreover, the cumulative dose–volume histograms (DHVs) were evaluated. The median follow-up period for alive patients is 30 months (range, 21–44+ months). Results : Tumor remission was observed in 17 patients: in 11 cases, complete remission was achieved and in six cases, only partial remission was possible. One patient was lost to follow-up before the first response evaluation. The median survival for all patients is 22 months (range, 3–44+ months). Ten patients are alive and seven died. In six cases, the cause of death was head and neck tumor and in one died due to pancreatic cancer (second primary). No late bone post-radiation complication was seen. The highest radiotherapy doses were observed in the retromolar regions. The mean percentage doses at the right and left retromolar regions were 101.3±3.8% (range, 90.2–109.1%) and 101.7±2.5% (range, 95.2–105.8%), respectively. Lower doses were seen in ascending ramus (the mean percentage doses at right and left ascending ramus were 97.3±8.5% and 97.8±7.6%, respectively), the molar regions (the mean percentage doses at right and left molar regions were 86.0±13.5% and 88.1±12.9%, respectively), and at the mandibular condyles (the mean percentage doses at the right and left mandibular condyles were 72.6±18% and 77.0±16.5%, respectively). The volume of the mandible ranged from 60.1 to 110.1cm 3 (a mean of of 82.3cm 3 ). In all patients, the maximum dose absorbed in the mandible was higher than the dose prescribed in the ICRU point and the mean maximum dose absorbed in the mandible was 105.7±2.1% (range, 102.4–110.6%). The percentage of mandibular volume receiving a dose higher than prescribed was 28.6±14.9% (range 10.2–58.1%). The area underlying the DVH curve, the maximum mandibular doses and the retromolar doses did not appear to statistically depend on use of wedge or mandibular volume. Conclusions : Radiotherapy for oropharyngeal cancer is associated with high doses to the retromolar mandibular regions (the dose can be higher than prescribed in the ICRU reference point), ascending ramus and molar regions. Lower doses are absorbed at the condyles and mental symphysis. The single dose point (for example, the ICRU reference point) could be not used as a representative for the mandibular dose. In our small series of patients treated with hyperfractionated irradiation, these dose heterogeneities were not correlated to the patient- and treatment-related factors and are not related to the increased risk of late bone complications. The clinical relevance of mandibular dose distribution remains to be established in larger series of patients treated with conventionally and unconventionally fractionated irradiation.