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Background: Aim was to compare the efficacy of interventional radiotherapy (IRT) boost vs. external beam radiotherapy (EBRT) boost after chemoradiation (CCRT) in patients with anal cancer (AC)., Methods: The P.I.C.O. framework was: in patients with AC [P], is IRT boost [I] superior to EBRT boost [C] in terms of local control (LC), cancer specific survival (CSS), overall survival (OS), distant meta-static free Survival (DMFS), colostomy free survival (CFS) and toxicity [O]?, Results: 651 patients were analyzed. The median 5-year locoregional control rates was 87.8% in the IRT boost group versus 72.8% in the EBRT boost group. The 5-year cancer-specific survival rate was 91% in the IRT boost group versus 78% in the EBRT boost group. 5-years overall survival was 74.6% in IRT boost versus 67.7% in the EBRT boost. 5-years disease metastasis-free survival rate was 92.9% in IRT boost group vs. 85.6% for the EBRT boost group. Cancer-free survival rate was 76.8% in the IRT group vs. 63.1% in the EBRT boost group. Acute toxicity above grade 2 was less common in the IRT boost group while chronic toxicity was similar between both groups., Conclusion: IRT boost after CCRT could lead to better outcomes than EBRT boost in treating AC., Competing Interests: Declarations. Conflict of interest: All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript. Ethical approval: A systematic review did not require ethics approval. Consent informed: A systematic review did not require a signed consent informed. Consent for publication: Not applicable., (© 2024. Italian Society of Medical Radiology.)

Purpose: Breast cancer is the most frequently diagnosed tumour, representing nearly 30% of all new cases in women. Radiotherapy (RT) plays a crucial role in the management of breast cancer. The objective of this study is to assess modesty in patients undergoing RT for breast cancer and take their suggestions and ideas into consideration to enhance the quality of treatment in this regard., Methods: The study enrolled 555 breast cancer patients undergoing adjuvant RT in three Italian centres. Patients completed a self-test questionnaire assessing their comfort level concerning modesty during therapy and their relationship with strangers and healthcare professionals. The impact of religious views and potential changes in sexuality were also examined., Results: Results showed that modesty was a common concern across the overall cohort of patients, with discomfort in being undressed during RT correlating with discomfort experienced in other daily life situations. Most patients felt more at ease with same sex healthcare workers. Age was also a major factor with younger patients generally feeling more comfortable with healthcare workers of the same age group. Interestingly, the surgical technique used (mastectomy vs. quadrantectomy) did not significantly influence modesty perceptions. Patients provided valuable suggestions to improve privacy and modesty during RT., Conclusion: This study demonstrates that modesty is an important issue for women undergoing RT, which can be influenced by personal characteristics and hospital-related factors. A reflection about the need to address modesty concerns and to incorporate dedicated interventions for protecting patients' physical and emotional well-being is warranted. Initiatives to improve communication, involvement, and body image support should also be integrated into the care path of patients to better their overall therapeutic experience. This study paves the way for broader research and interventions in daily cancer care., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background/aim: The current standard for anal cancer treatment is essentially a 'one size fits all' approach where the dose of radiotherapy is similar whether the tumor is very small or very large. Trials are ongoing to evaluate dose de-escalation or escalation in localized disease depending on tumor size. The aim of the study was to assess results of a personalized approach involving dose stratification by stage and boost dose adjusted according to tumor early response., Patients and Methods: We retrospectively reviewed squamous cell anal cancer (SCAC) patients treated between 2011 and 2021 by long-course intensity-modulated radiotherapy (IMRT) and concomitant chemotherapy (CT); a sequential boost could be administered by IMRT or interventional radiotherapy (IRT) to obtain a total equivalent dose in 2 Gy (EQD2) of 54-60 Gy., Results: We analyzed 110 patients (61% T3-4 stage, 71% node-positive). A total of 68.2% of patients received a sequential boost, mainly by IRT; median total EQD2 to primary site was 59.3 Gy. Acute ≥G3 toxicity rate was 36.4%. Median follow-up (FUP) was 35.4 months. A total of 83% of patients achieved clinical complete response (cCR); locoregional recurrence (LRR) occurred in 20.9% and distant metastases in 6.4% of cases. A total of 12.7% patients underwent salvage surgery. A total of 25.5% of patients reported ≥G2 and 4.5% ≥G3 late toxicity. The estimated 3-year overall survival, disease-free survival and colostomy-free survival were 92%, 72% and 84% respectively; 3-year-LRR was 22%. Nodal stage was associated with poorer cCR probability and higher LRR (p<0.05)., Conclusion: Our results on a large cohort of patients with locally advanced SCAC and long FUP time confirmed the efficacy of IMRT; high local control and manageable toxicity also suggest IRT as a promising method in treatment personalization., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: Monomorphic ventricular tachycardia (VT) is a life-threatening condition often observed in patients with structural heart disease. Ventricular tachycardia ablation through radiation therapy (VT-ART) for sustained monomorphic ventricular tachycardia seems promising, effective, and safe. VT-ART delivers focused, high-dose radiation, usually in a single fraction of 25 Gy, allowing ablation of VT by inducing myocardial scars. The procedure is fully non-invasive; therefore, it can be easily performed in patients with contraindications to invasive ablation procedures. Definitive data are lacking, and no direct comparison with standard procedures is available., Discussion: The aim of this multicenter observational study is to evaluate the efficacy and safety of VT-ART, comparing the clinical outcome of patients undergone to VT-ART to patients not having received such a procedure. The two groups will not be collected by direct, prospective accrual to avoid randomization among the innovative and traditional arm: A retrospective selection through matched pair analysis will collect patients presenting features similar to the ones undergone VT-ART within the consortium (in each center independently). Our trial will enroll patients with optimized medical therapy in whom endocardial and/or epicardial radiofrequency ablation (RFA), the gold standard for VT ablation, is either unfeasible or fails to control VT recurrence. Our primary outcome is investigating the difference in overall cardiovascular survival among the group undergoing VT-ART and the one not exposed to the innovative procedure. The secondary outcome is evaluating the difference in ventricular event-free survival after the last procedure (i.e., last RFA vs. VT-ART) between the two groups. An additional secondary aim is to evaluate the reduction in the number of VT episodes comparing the 3 months before the procedure to the ones recorded at 6 months (from the 4th to 6th month) following VT-ART and RFA, respectively. Other secondary objectives include identifying the benefits of VT-ART on cardiac function, as evaluated through an electrocardiogram, echocardiographic, biochemical variables, and on patient quality of life. We calculated the sample size (in a 2:1 ratio) upon enrolling 149 patients: 100 in the non-exposed control group and 49 in the VT-ART group. Progressively, on a multicentric basis supervised by the promoting center in the VT-ART consortium, for each VT-ART patient enrollment, a matched pair patient profile according to the predefined features will be shared with the consortium to enroll a patient that has not undergone VT-ART., Conclusion: Our trial will provide insight into the efficacy and safety of VT-ART through a matched pair analysis, via an observational, multicentric study of two groups of patients with or without VT-ART in the multicentric consortium (with subgroup stratification into dynamic cohorts)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cellini, Narducci, Pavone, Bencardino, Perna, Pinnacchio, Chiesa, Massaccesi, Gambacorta, Manfrida, Longo, Mannocci, Di Gregorio, Boldrini, Tagliaferri, Indovina, Placidi, Stimato, Spera, Scacciavillani, Crea, Valentini and Pelargonio.)

Background and Purpose: A prognostic scoring system based on laboratory inflammation parameters, [Hemo-Eosinophils-Inflammation (HEI) index], including baseline hemoglobin level, the systemic inflammatory index and eosinophil count was recently proposed in patients with squamous cell carcinoma of the anus (ASCC). HEI was shown to discriminate disease-free (DFS) and overall (OS) survival in ASCC patients treated with concurrent chemoradiation (CRT). We tested the accuracy of the model on a multicentric cohort for external validation., Materials and Methods: Patients treated with CRT were enrolled. The Kaplan-Meier curves for DFS and OS based on HEI risk group were calculated and the log-rank test was used. Cox proportional hazards models were used to assess the prognostic factors for DFS and OS. The exponential of the regression coefficients provided an estimate of the hazard ratio (HR). For model discrimination, we determined Harrell's C-index, Gönen & Heller K Index and the explained variation on the log relative hazard scale., Results: A total of 877 patients was available. Proportional hazards were adjusted for age, gender, tumor-stage, and chemotherapy. Two-year DFS was 77 %(95 %CI:72.0-82.4) and 88.3 %(95 %CI:84.8-92.0 %) in the HEI high- and low- risk groups. Two-year OS was 87.8 %(95 %CI:83.7-92.0) and 94.2 %(95 %CI:91.5-97). Multivariate Cox proportional hazards model showed a HR = 2.02(95 %CI:1.25-3.26; p = 0.004) for the HEI high-risk group with respect to OS and a HR = 1.53(95 %CI:1.04-2.24; p = 0.029) for DFS. Harrel C-indexes were 0.68 and 0.66 in the validation dataset, for OS and DFS. Gonen-Heller K indexes were 0.67 and 0.71, respectively., Conclusion: The HEI index proved to be a prognosticator in ASCC patients treated with CRT. Model discrimination in the external validation cohort was acceptable., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: Bone metastases frequently occur during malignant disease. Palliative radiation therapy (PRT) is a crucial part of palliative care because it can relieve pain and improve patients' quality of life. Often, a clinician's survival estimation is too optimistic. Prognostic scores (PSs) can help clinicians tailor PRT indications to avoid over- or undertreatment. Although the PS is supposed to aid radiation oncologists (ROs) in palliative-care scenarios, it is unclear what type of support, and to what extent, could impact daily clinical practice., Methods and Materials: A national-based investigation of the prescriptive decisions on simulated clinical cases was performed in Italy. Nine clinical cases from real-world clinical practice were selected for this study. Each case description contained complete information regarding the parameters defining the prognosis class according to the PS (in particular, the Mizumoto Prognostic Score, a validated PS available in literature and already applied in some clinical trials). Each case description contained complete information regarding the parameters defining the prognosis class according to the PS. ROs were interviewed through questionnaires, each comprising the same 3 questions per clinical case, asking (1) the prescription after detailing the clinical case features but not the PS prognostic class definition; (2) whether the RO wanted to change the prescription once the PS prognostic class definition was revealed; and (3) in case of a change of the prescription, a new prescriptive option. Three RO categories were defined: dedicated to PRT (RO-d), nondedicated to PRT (RO-nd), and resident in training (IT). Interviewed ROs were distributed among different regions of the country., Results: Conversion rates, agreements, and prescription trends were investigated. The PS determined a statistically significant 11.12% of prescription conversion among ROs. The conversion was higher for the residents and significantly higher for worse prognostic scenario subgroups, respectively. The PS improved prescriptive agreement among ROs (particularly for worse-prognostic-scenario subgroups). Moreover, PS significantly increased standard prescriptive approaches (particularly for worse-clinical-case presentations)., Conclusions: To the best of our knowledge, the PROPHET study is the first to directly evaluate the potential clinical consequences of the regular application of any PS. According to the Prophet study, a prognostic score should be integrated into the clinical practice of palliative radiation therapy for bone metastasis and training programs in radiation oncology., (© 2022 The Author(s).)

Melanoma is an extremely aggressive tumor and is considered to be an extremely immunogenic tumor because compared to other cancers it usually presents a well-expressed lymphoid infiltration. The aim of this paper is to perform a multidisciplinary comprehensive review of the evidence available about the combination of radiotherapy and immunotherapy for melanoma. Radiation, in fact, can increase tumor antigens visibility and promote priming of T cells but can also exert immunosuppressive action on tumor microenvironment. Combining radiotherapy with immunotherapy provides an opportunity to increase immunostimulatory potential of radiation. We therefore provide the latest clinical evidence about radiobiological rationale, radiotherapy techniques, timing, and role both in advanced and systemic disease (with a special focus on ocular melanoma and brain, liver, and bone metastases) with a particular attention also in geriatric patients. The combination of immunotherapy and radiotherapy seems to be a safe therapeutic option, supported by a clear biological rationale, even though the available data confirm that radiotherapy is employed more for metastatic than for non-metastatic disease. Such a combination shows promising results in terms of survival outcomes; however, further studies, hopefully prospective, are needed to confirm such evidence.

Background: People living with HIV (PLWH) are generally known to suffer from a lower quality of life compared to the one of general population, but still very few is known about the self-perception of quality of life when comparing HIV to non-communicable diseases. We performed a comprehensive assessment of patient's reported outcomes measures (PROMs) among PLWH and patients affected by other chronic conditions (OC) such as diabetes mellitus type 1, rheumatoid arthritis, breast cancer in hormonal therapy, in order to investigate differences in PROMs outcomes between PLWH and other pathologies., Methods: A cross-sectional observational study was performed by using questionnaires investigating health-related quality of life (Medical Outcomes Study Short Form 36-item Health Survey), work productivity (WPI), and global health status (EQ-5D-3L). They were administered to patients affected by chronic diseases consecutively observed at a single University Hospital during a 10 months period, with comparable disease related aspects. Logistic regression analysis was used to analyze the association between disease group (HIV vs OC) and PROMs., Results: 230 patients were enrolled (89 PLWH, 143 OC). Mean age: 49 years (SD 10), mean time of disease 12 years (10), 96% were Caucasian, 35% assumed polypharmacy, 42% of male were PLWH versus 16% OC (p < 0.001), 19% PLWH versus 6% OC had clinical complications (p < 0.001). HIV infection was independently associated to a better health-related quality of life in several domains compared with the other conditions, except in mental health, whereas a worst health-related quality of life in most domains was reported by older patients and those experiencing polypharmacy., Conclusions: In this cohort of patients with chronic conditions followed within the same health setting, PLWH showed better self-reported health outcomes compared to other chronic conditions with comparable characteristics of chronicity. The potential detrimental role of older age and polypharmacy in most outcomes suggests the need of longitudinal assessment of PROMs in clinical practice., (© 2022. The Author(s).)

Aims: Between 11 to 14% of patients with locally advanced rectal cancer (LARC) have positive lateral pelvic lymph nodes (LPLN) at diagnosis, related to a worse prognosis with a 5-year survival rate between 30 to 40%. The best treatment choice for this group of patients is still a challenge. The optimal radiotherapy (RT) dose for LPLN patients has been investigated. Methods: We retrospectively collected data from LARC patients with LPLN at the primary staging MRI, treated in our center from March 2003 to December 2020. Patients underwent a neoadjuvant concomitant chemo-radiotherapy (CRT) treatment on the primary tumor (T), mesorectum, and pelvic nodes, associated with a fluoride-based chemotherapy. The total reached dose was 45 Gy at 1.8 Gy/fr on the elective sites and 55 Gy at 2.2 Gy/fr on the disease and mesorectum. Patients were divided in two groups based on whether they received a simultaneous integrated RT boost on the LPLN or not. Overall Survival (OS), Disease Free Survival (DFS), Metastasis Free Survival (MFS), and Local Control (LC) were evaluated in the whole group and then compared between the two groups. Results: A total of 176 patients were evaluated: 82 were included in the RT boost group and 94 in the non-RT boost group. The median follow-up period was 57.8 months. All the clinical endpoint (OS, DFS, MFS, LC), resulted were affected by the simultaneous integrated boost on LPLN with a survival rate of 84.7%, 79.5%, 84.1%, and 92%, respectively, in the entire population. From the comparison of the two groups, there was a statistical significance towards the RT boost group with a p < 0.006, 0.030, 0.042, 0.026, respectively. Conclusions: Concomitant radiotherapy boost on positive LPLN has shown to be beneficial on the survival outcomes (OS, DFS, MFR, and LC) in patients with LARC and LPLN. This analysis demonstrates that a higher dose of radiotherapy on positive pelvic lymph nodes led not only to a higher local control but also to a better survival rate. These results, if validated by future prospective studies, can bring a valid alternative to the surgery dissection without the important side effects and permanent disabilities observed during the years.

The modern management of esophageal cancer is crucially based on a multidisciplinary and multimodal approach. Radiotherapy is involved in neoadjuvant and adjuvant settings; moreover, it includes radical and palliative treatment intention (with a focus on the use of a stent and its potential integration with radiotherapy). In this review, the above-mentioned settings and approaches will be described. Referring to available international guidelines, the background evidence bases will be reviewed, and the ongoing, more relevant trials will be outlined. Target definitions and radiotherapy doses to administer will be mentioned. Peculiar applications such as brachytherapy (interventional radiation oncology), and data regarding innovative approaches including MRI-guided-RT and radiomic analysis will be reported. A focus on the avoidance of surgery for major clinical responses (particularly for SCC) is detailed.

Introduction: The COVID-19 pandemic has challenged healthcare systems worldwide over the last few months, and it continues to do so. Although some restrictions are being removed, it is not certain when the pandemic is going to be definitively over. Pandemics can be seen as a highly complex logistic scenario. From this perspective, some of the indications provided for palliative radiotherapy (PRT) during the COVID-19 pandemic could be maintained in the future in settings that limit the possibility of patients achieving symptom relief by radiotherapy. This paper has two aims: (1) to provide a summary of the indications for PRT during the COVID-19 pandemic; since some indications can differ slightly, and to avoid any possible contradictions, an expert panel composed of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) and the Palliative Care and Supportive Therapies Working Group (AIRO-palliative) voted by consensus on the summary; (2) to introduce a clinical care model for PRT [endorsed by AIRO and by a spontaneous Italian collaborative network for PRT named "La Rete del Sollievo" ("The Net of Relief")]. The proposed model, denoted "No cOmpRoMise on quality of life by pALliative radiotherapy" (NORMALITY), is based on an AIRO-palliative consensus-based list of clinical indications for PRT and on practical suggestions regarding the management of patients potentially suitable for PRT but dealing with highly complex logistics scenarios (similar to the ongoing logistics limits due to COVID-19)., Material and Methods: First, a summary of the available literature guidelines for PRT published during the COVID-19 pandemic was prepared. A systematic literature search based on the PRISMA approach was performed to retrieve the available literature reporting guideline indications fully or partially focused on PRT. Tables reporting each addressed clinical presentation and respective literature indications were prepared and distributed into two main groups: palliative emergencies and palliative non-emergencies. These summaries were voted in by consensus by selected members of the AIRO and AIRO-palliative panels. Second, based on the summary for palliative indications during the COVID-19 pandemic, a clinical care model to facilitate recruitment and delivery of PRT to patients in complex logistic scenarios was proposed. The summary tables were critically integrated and shuffled according to clinical presentations and then voted on in a second consensus round. Along with the adapted guideline indications, some methods of performing the first triage of patients and facilitating a teleconsultation preliminary to the first in-person visit were developed., Results: After the revision of 161 documents, 13 papers were selected for analysis. From the papers, 19 clinical presentation items were collected; in total, 61 question items were extracted and voted on (i.e., for each presentation, more than one indication was provided from the literature). Two tables summarizing the PRT indications during the COVID-19 pandemic available from the literature (PRT COVID-19 summary tables) were developed: palliative emergencies and palliative non-emergencies. The consensus of the vote by the AIRO panel for the PRT COVID-19 summary was reached. The PRT COVID-19 summary tables for palliative emergencies and palliative non-emergencies were adapted for clinical presentations possibly associated with patients in complex clinical scenarios other than the COVID-19 pandemic. The two new indication tables (i.e., "Normality model of PRT indications") for both palliative emergencies and palliative non-emergencies were voted on in a second consensus round. The consensus rate was reached and strong. Written forms facilitating two levels of teleconsultation (triage and remote visits) were also developed, both in English and in Italian, to evaluate the patients for possible indications for PRT before scheduling clinical visits., Conclusion: We provide a comprehensive summary of the literature guideline indications for PRT during COVID-19 pandemic. We also propose a clinical care model including clinical indications and written forms facilitating two levels of teleconsultation (triage and remote visits) to evaluate the patients for indications of PRT before scheduling clinical visits. The normality model could facilitate the provision of PRT to patients in future complex logistic scenarios., (© 2021. The Author(s).)

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.

Introduction: In radiotherapy, palliative patients are often suboptimal managed and patients experience long waiting times. Event-logs (recorded local files) of palliative patients, could provide a continuative decision-making system by means of shared guidelines to improve patient flow. Based on an event-log analysis, we aimed to accurately understand how to successively optimize patient flow in palliative care., Methods: A process mining methodology was applied on palliative patient flow in a high-volume radiotherapy department. Five hundred palliative radiation treatment plans of patients with bone and brain metastases were included in the study, corresponding to 290 patients treated in our department in 2018. Event-logs and the relative attributes were extracted and organized. A process discovery algorithm was applied to describe the real process model, which produced the event-log. Finally, conformance checking was performed to analyze how the acquired event-log database works in a predefined theoretical process model., Results: Based on the process discovery algorithm, 53 (10%) plans had a dose prescription of 8 Gy, 249 (49.8%) plans had a dose prescription of 20 Gy and 159 (31.8%) plans had a dose prescription of 30 Gy. The remaining 39 (7.8%) plans had different dose prescriptions. Considering a median value, conformance checking demonstrated that event-logs work in the theoretical model., Conclusions: The obtained results partially validate and support the palliative patient care guideline implemented in our department. Process mining can be used to provide new insights, which facilitate the improvement of existing palliative patient care flows., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Background: Elderly patients are often excluded from advanced treatments owing to clinical complexity or frailty. Magnetic resonance-guided radiotherapy (MRgRT) represents a new frontier of radiotherapy delivery that can play an important role in the management of these patients., Aim: To assess MRgRT feasibility in elderly patients, describe their compliance with this treatment, and provide a scoring system for elderly patient selection., Methods: Patients aged >75 years were enrolled. No restrictions on tumor site, staging, or treatment intent were applied. Patients underwent joint radiation oncology-geriatrics visits to assess the feasibility of MRgRT and to identify the most significant items (i.e. clinical variables) for the setup of a scoring system. The proposed scoring system was then internally validated on a prospectively enrolled cohort of elderly patients who were candidates for MRgRT., Results: Thirty patients were enrolled between February and March 2018. Their mean age was 81.4 ± 3.4 years (range 75-88). Radiotherapy intent was curative in 26 patients; 14 patients were considered frail at screening tests before radiotherapy. Twelve items were identified as clinically significant for the setup of the MASTER score (MRI-Guided Radiotherapy Selection Elderly Score) score. Validation of the score showed 100% reliability, with no patient discharged after selection., Conclusions: MRgRT appears to be feasible in elderly patients and the MASTER score is proposed to support clinical decision-making in recommending elderly patients for this technology.

This study aimed to define the maximum tolerated dose (MTD) of temozolomide (TMZ) concurrent with radiotherapy (RT) after high-dose methotrexate (HD-MTX) for newly diagnosed primary central nervous system lymphoma (PCNSL). Adult patients with PCNSL were treated according to a response-adapted strategy. HD-MTX (3.5 g/m 2 ) was followed by concomitant RT and escalating TMZ (50-60-75 mg/m 2 /day, 5 days/week). The total radiation dose was modulated according to the patient's response to HD-MTX. All patients received 30 Gy to the whole brain plus leptomeninges to C2, including the third posterior of the orbital cavity (clinical target volume 2; CTV2), plus 6, 10, or 16 Gy to the primary site, including the residual mass (CTV1), if a complete response (CR), partial response (PR)/stable disease (SD), or progressive disease (PD) was observed, respectively. Acute toxicities were graded according to the RTOG-EORTC criteria. Dose-limiting toxicity (DLT) was defined as grade 4 hematological toxicity or grade 3-4 hepatic toxicity, although 75 mg/m 2 /day was the maximum dose regardless of DLT. Neurocognitive function was evaluated using the Mini-Mental State Examination. Three patients were enrolled at each TMZ dose level (total = 9 patients). Twelve lesions were treated. Six patients received 2 cycles of HD-MTX, while 3 received only 1 cycle because of hepatic or renal toxicity. All patients completed chemoradiotherapy without interruptions. No DLT events were recorded. TMZ appears to be tolerable at a dose of 75 mg/m 2 /day when administered concomitantly with radiotherapy and after HD-MTX.

The standard care for metastatic breast cancer (MBC) is systemic therapies with imbrication of focal treatment for symptoms. Recently, thanks to implementation of radiological and metabolic exams and development of new target therapies, oligometastatic and oligoprogressive settings are even more common-paving the way to a paradigm change of focal treatments role. In fact, according to immunophenotype, radiotherapy can be considered with radical intent in these settings of patients. The aim of this literature review is to analyze available clinical data on prognosis of bone metastases from breast cancer and benefits of available treatments for developing a practical guide for clinicians.

Objective: We assessed the prognostic value of several FDG PET/CT parameters, measured within the primary tumor and the involved lymph nodes, before definitive radio-chemotherapy (RCT) in anal cancer patients., Methods: Anal cancer patients with positive baseline FDG PET/CT who underwent definitive RCT from May 2011 to February 2018 were retrospectively assessed. Primary tumour (T)-SUVmax, T-SUVpeak, T-SUVmean, T-MTV, T-TLG, whole-body (WB) MTV, and WB-TLG were measured. Kaplan-Meier curves, Cox-regression analysis, and logistic regression machine-learning technique were used to test for associations between clinical data, metabolic parameters, and outcomes as overall survival (OS), disease-specific survival (DSS), metastatic-free survival (MFS), disease-free survival (DFS), local relapse-free survival (LRFS), and colostomy-free survival (CFS)., Results: Fifty-nine patients were included in the study. Median follow-up was 28 months. Higher pre-treatment WB-MTV, T-TLG, and WB-TLG were associated with worse OS (p = 0.025, 0.021, and 0.02, respectively). PET parameters resulted also statistically significant for DSS, DFS, and CFS (p = 0.032, 0.043, 9 × 10 -4 for WB-TLG). Cox analysis showed that PET parameters are significant predictors of OS, DSS, DFS, CFS, and LRFS. On multivariate analysis, age, stage, T-SUVpeak, WB-MTV, and T-TLG resulted significantly related to OS. A further stratification for patients with advanced stage (cT3-4 any N or any cT, N + ) showed that MTV and TLG, measured within the primary tumor and the involved nodes, are significantly higher in patients with a worse prognosis. In this subgroup, cut-off values of T- and WB-TLG as well as T- and WB-MTV showed a statistically significant correlation with clinical outcomes., Conclusions: Pre-treatment metabolic parameters measured within the primary tumor and the involved nodes may represent additional new biomarkers for estimating prognosis in anal cancer patients, especially in advanced stage patients.

Background: Palliative antalgic treatments represent an issue for clinical management and a challenge for scientific research. Radiotherapy (RT) plays a central role. Techniques such as stereotactic body radiotherapy (SBRT) were largely investigated in several phase 2 studies with good symptom response, becoming widely adopted. However, evidence from randomized, direct comparison of RT and SBRT is still lacking., Methods/design: The PREST trial was designed as an interventional study without medicinal treatment. It is a phase 3, open-label, multicentric trial randomized 1:1. Inclusion criteria include painful spinal bone metastases presenting with a pain level > 4 (or > 1 if being treated with an analgesic) on the Numeric Rating Scale (NRS); expected intermediate/high prognosis (greater than 6 months) according to the Mizumoto prognostic score; low spine instability neoplastic score (SINS) sores (< 7); magnetic resonance imaging (MRI) assessment of the bulky lesion. Patients will be assigned to either standard conventional radiotherapy involving 4 Gy × 5 fractions (fx) to the whole involved vertebra or SBRT by intensity modulated radiotherapy with simultaneous integrated boost (IMRT-SIB) involving 7 Gy × 3 fx to the whole involved vertebra + 10 Gy × 3 fx on the macroscopic lesion (gross tumor volume (GTV)). In the experimental arm, the GTV will be contoured by registration with baseline MRI., Discussion: The primary endpoint is overall pain reduction, defined in terms of variation between baseline and 3-month evaluation; pain will be measured using the NRS. Secondary endpoints include pain control duration; retreatment rates (after a minimum interval of 1 month); local control assessed with RECIST criteria; symptom progression free survival; progression-free survival; overall survival; and quality of life (at 0, 30, and 90 days). Accrual of 330 lesions is planned. The experimental arm is expected to have an improvement in overall pain response rates of 15% with respect to the standard arm (60% according to Chow et al. (Int J Radiat Oncol Biol Phys. 82(5):1730-7, 2012))., Trial Registration: ClinicalTrials.gov, NCT03597984 . Registered on July 2018.

Purpose: Purpose of this study was to retrospectively review our experience of multidisciplinary clinic providing a joint approach by radiation oncologist and anesthetist for patients with cancer pain to evaluate the adequacy and the IMprovement in MAnagement (IM-MA study) of this symptom., Methods: A Team for Pain Management (TPM) represented by radiation oncologist and anesthetist weekly provided consultations to patient presenting cancer pain. TPM prospectively reported epidemiologic, symptomatic, and pharmacological data. TPM modified pain therapy and indicated antalgic radiotherapy. Patients were evaluated at baseline and after 4 weeks after intervention., Results: From November 2015 to April 2016, 65 patients were evaluated by TPM. At the baseline, 18 patients (27.7%) were undertreated (i.e., receiving inadequate pain management); furthermore, 27 patients (41.5%) despite receiving strong opioids had uncontrolled pain. After 4 weeks from intervention, undertreated patients were reduced to 1.53%. For those patients undergone to radiotherapy, response at 34 weeks was scored as follows: complete response 28.8%, partial response 46.7%, pain progression 0.95%, indeterminate response 23.8%., Conclusions: A multidisciplinary Team for Pain Management improved the clinical management, optimizing pain control and increasing adequacy of pharmacological management. The TPM intervention seems particularly worth for patients presenting specific features including BTcP, neuropathic pain, severe pain due to bone metastases, and any potential candidate to radiotherapy. Larger series and QoL questionnaires are required to confirm these results.

Objectives: Recently, radiomic analysis has gained attention as a valuable instrument for the management of oncological patients. The aim of the study is to isolate which features of magnetic resonance imaging (MRI)-based radiomic analysis have to be considered the most significant predictors of metastasis in oncological patients with spinal bone marrow metastatic disease., Materials and Methods: Eight oncological patients (3 lung cancer; 1 prostatic cancer; 1 esophageal cancer; 1 nasopharyngeal cancer; 1 hepatocarcinoma; 1 breast cancer) with pre-radiotherapy MR imaging for a total of 58 dorsal vertebral bodies, 29 metastatic and 29 non-metastatic were included. Each vertebral body was contoured in T1 and T2 weighted images at a radiotherapy delineation console. The obtained data were transferred to an automated data extraction system for morphological, statistical and textural analysis. Eighty-nine features for each lesion in both T1 and T2 images were computed as the median of by-slice values. A Wilcoxon test was applied to the 89 features and the most statistically significant of them underwent to a stepwise feature selection, to find the best performing predictors of metastasis in a logistic regression model. An internal cross-validation via bootstrap was conducted for estimating the model performance in terms of the area under the curve (AUC) of the receiver operating characteristic., Results: Of the 89 textural features tested, 16 were found to differ with statistical significance in the metastatic vs non-metastatic group. The best performing model was constituted by two predictors for T1 and T2 images, namely one morphological feature (center of mass shift) (p value < 0.01) for both datasets and one histogram feature minimum grey level (p value < 0.01) for T1 images and one textural feature (grey-level co-occurrence matrix joint variance (p value < 0.01) for T2 images. The internal cross-validation showed an AUC of 0.8141 (95% CI 0.6854-0.9427) in T1 images and 0.9116 (95% CI 0.8294-0.9937) in T2 images., Conclusions: The results suggest that MRI-based radiomic analysis on oncological patients with bone marrow metastatic disease is able to differentiate between metastatic and non-metastatic vertebral bodies. The most significant predictors of metastasis were found to be based on T2 sequence and were one morphological and one textural feature.

Malignant spinal bone marrow disorders are one of the major causes of significant morbidity and reduction in quality of life in oncological patients. Thus, the characterization of these conditions is of crucial importance in the management of these patients. Magnetic resonance (MR) imaging plays a vital role in differentiation between benign and malignant spinal bone marrow disorders. However, morphological imaging features, based on T1 and T2 relaxation properties, might fail in differentiating between these conditions because signal characteristics may overlap. Quantitative MR imaging based on diffusion weighted imaging (DWI) and apparent diffusion coefficient (ADC) values has been proved to help in defining the nature of the lesion. The aims of this paper were: to review basic principles of DWI technique and ADC maps, to describe DWI and ADC maps appearances of normal vertebral bone marrow briefly, to discuss the DWI and ADC maps characteristics in vertebral malignant lesions, to provide indications for differential diagnosis between malignant and benign lesions.

Introduction: The role of prophylactic inguinal irradiation (PII) in the treatment of anal cancer patients is controversial. We developped an innovative algorithm based on the Machine Learning (ML) allowing the tailoring of the prescription of PII., Results: Once verified on the independent testing set, J48 showed the better performances, with specificity, sensitivity, and accuracy rates in predicting relapsing patients of 86.4%, 50.0% and 83.1% respectively (vs 36.5%, 90.4% and 80.25%, respectively, for LR)., Methods: We classified 194 anal cancer patients with Logistic Regression (LR) and other 3 ML techniques based on decision trees (J48, Random Tree and Random Forest), using a large set of clinical and therapeutic variables. We tested obtained ML algorithms on an independent testing set of 65 anal cancer patients. TRIPOD (Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis) methodology was used for the development, the Quality Assurance and the description of the experimental procedures., Conclusion: In an internationally approved quality assurance framework, ML seems promising in predicting the outcome of patients that would benefit or not of the PII. Once confirmed in larger and/or multi-centric databases, ML could support the physician in tailoring the treatment and in deciding if deliver or not the PII., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

To validate autocontouring software (AS) in a clinical practice including a two steps delineation quality assurance (QA) procedure.The existing delineation agreement among experts for rectal cancer and the overlap and time criteria that have to be verified to allow the use of AS were defined.Median Dice Similarity Coefficient (MDSC), Mean slicewise Hausdorff Distances (MSHD) and Total-Time saving (TT) were analyzed.Two expert Radiation Oncologists reviewed CT-scans of 44 patients and agreed the reference-CTV: the first 14 consecutive cases were used to populate the software Atlas and 30 were used as Test.Each expert performed a manual (group A) and an automatic delineation (group B) of 15 Test patients.The delineations were compared with the reference contours.The overlap between the manual and automatic delineations with MDSC and MSHD and the TT were analyzed.Three acceptance criteria were set: MDSC ≥ 0.75, MSHD ≤1mm and TT sparing ≥ 50%.At least 2 criteria had to be met, one of which had to be TT saving, to validate the system.The MDSC was 0.75, MSHD 2.00 mm and the TT saving 55.5% between group A and group B. MDSC among experts was 0.84.Autosegmentation systems in rectal cancer partially met acceptability criteria with the present version., Competing Interests: The authors report no conflicts of interest. The authors are alone responsible for the content and writing of the paper.

Purpose: The aim of this study is to test a novel multiparametric imaging guided procedure for high-dose-rate brachytherapy in anal canal cancer, in order to evaluate the feasibility and safety., Material and Methods: For this analysis, we considered all consecutive patients who underwent magnetic resonance/computed tomography image adapted brachytherapy (MR/CT-IABT) treated from February 2012 to July 2014. To conduct this project, we formed a working group that established the procedure and identified the indicators and benchmarks to evaluate the feasibility and safety. We considered the procedure acceptable if 90% of the indicators were consistent with the benchmarks. Magnetic resonance imaging with contrast and diffusion weighted imaging were performed with an MRI-compatible dummy applicator in the anus to define the position of the clinical target volume disease and biological information. A pre-implantation treatment planning was created in order to get information on the optimal position of the needles. Afterwards, the patient underwent a simulation CT and the definite post-implantation treatment planning was created., Results: We treated 11 patients (4 men and 7 women) with MR/CT-IABT and we performed a total of 13 procedures. The analysis of indicators for procedure evaluation showed that all indicators were in agreement with the benchmark. The dosimetric analysis resulted in a median of V200, V150, V100, V90, V85, respectively of 24.6%, 53.4%, 93.5%, 97.6%, and 98.7%. The median coverage index (CI) was 0.94, the median dose homogeneity index (DHI) was 0.43, the median dose non-uniformity ratio (DNR) resulted 0.56, the median overdose volume index (ODI) was 0.27. We observed no episodes of common severe acute toxicities., Conclusions: Brachytherapy is a possible option in anal cancer radiotherapy to perform the boost to complete external beam radiotherapy (EBRT). Magnetic resonance can also have biological advantages compared to the US. Our results suggest that the multiparametric MR/CT-IABT for anal cancer is feasible and safe. This new approach paves the way to prospective comparison studies between MRI and ultrasound-guided brachytherapy (USBT) in anal canal cancer.

Purpose: This study was planned to clarify the optimal treatment for squamous cell carcinoma of the rectum, an histological entity extremely rare., Methods: Ten patients with histologically proven squamous cell carcinoma of the rectum were treated with concomitant radiochemotherapy. Radiation therapy was delivered with a 3Dconformational multiple field technique to a dose ranging from 45 to 76.5 Gy, with 6-15 MV energy photons. Chemotherapy consisted of an antimetabolite drug in association with mitomycin C or oxaliplatin. Overall survival and disease free survival were considered in months from the end of the concomitant treatment., Results: All patients completed programmed radiochemotherapy treatment but two patients were excluded to the analysis. Six patients (75%) presented negative biopsy 6 months after the end of radiochemotherapy. Seven patients (87.5%) showed a tumour regression after initial treatment. Only 1 patient underwent salvage surgery. Considering a mean follow-up of 41.75 months, 7 patients are still disease free survivors. Only 1 patient developed local recurrence at 6 months and he died 14 months after abdomino-perineal resection., Conclusion: Primary radio chemotherapy, with a curative intent, could be considered the treatment modality of choice for squamous carcinoma of the rectum., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Given the poor compliance with adjuvant chemoradiotherapy (CRT) in gastric cancer reported in previous studies, a survey was conducted among 18 Italian institutions within the AIRO Gastrointestinal Group to investigate current treatment modalities, toxicities, and compliance with adjuvant CRT., Patients and Methods: Data from 348 patients operated on for gastric cancer were collected retrospectively from September 2000 to June 2008 and analyzed. The adjuvant treatments included CRT according to center guidelines. In multivariate analysis, acute hematological, gastrointestinal, and renal toxicity (according to the RTOG Acute Radiation Morbidity Scoring Criteria) and compliance with treatment were studied, as well as risk factors for local control, metastasis-free survival, disease-free survival, and overall survival., Results: Compliance with treatment was excellent: 95.7% of patients completed CRT. During CRT, acute G3-G4 ­hematological toxicity was 3.7% and acute G3-G4 gastrointestinal toxicity 4%. 78.4% of patients completed chemotherapy (CT), either before or after CRT. During CT acute G3-G4 hematological toxicity was 5.4% and acute G3-G4 gastrointestinal toxicity 6%. Overall, 74.1% of patients completed the prescribed treatment (CRT and CT). Doses greater than 4500 cGy did not compensate for more aggressive disease. The 5-year overall survival was 51%., Conclusions: The adjuvant treatment of gastric cancer within the AIRO group was diverse, but radiotherapy treatment was homogeneous (in terms of technique) and well tolerated. Toxicity was low and compliance with treatment was good during CRT; these results may be due to the radiotherapy technique applied. This survey could be used as a benchmark for further studies.

Background and Aim: To assess the effectiveness of the potential advantages with 3-dimensional-based treatment planning versus 2-dimensional pelvic bone-based treatment planning in patients with rectal cancer, controlled for clinical stage., Methods and Materials: Areas at risk from computed tomography in 30 patients were delineated: mesorectum, presacral, internal iliac, obturator and external iliac nodes. Two planning target volumes per patient were created: PTV&#95;T3 (M + PSN + ON + IIN) and PTV&#95;T4 (M + PSN + ON + IIN + EIN). Two- and 3-dimensional treatment plans for each planning target volume were calculated. Three analyses were performed: 1) mean volume receiving doses >95% and >105%; according to the percentage of prescribed dose to cover at least 95% of the planning target volume, the treatment plan was defined as optimal dose >95%, acceptable dose between 95% and 90%, inferior dose <90%; 2) comparison of the percentage of volume covered by the dose for 2- vs 3-dimensional; 3) determination of the doses at which the lack of volume coverage started to decrease significantly., Results: For PTV&#95;T3, the following was seen: 1) 2D vs 3D comparison showed optimal PTV&#95;T3 coverage in 76.7% and 96.7%, respectively; 2) 2D vs 3D TP coverage difference was significant between 29%-95% of the total dose; 3) the lack of volume coverage started at 30% for 2D and 89% for 3D. For PTV&#95;T4, the following was seen: 1) 2D vs 3D comparison showed an optimal PTV&#95;T4 coverage in 33.3% and 86.7%, respectively; 2) 2D vs 3D TP coverage difference was significant between 7%-97% of the total dose; 3) the lack of volume coverage started at 7% for 2D and 87% for 3D., Conclusions: The 3D treatment planning was superior to 2D treatment planning in covering areas at risk for pelvic recurrence in patients treated for rectal cancer. The areas with suboptimal coverage may lead to an increased risk of recurrence and should be correlated with the patterns of recurrence.

To analyse the impact of age and co-morbidities on compliance and outcomes in GBM patients enrolled in three prospective phase II trials. GBM patients (≥ 18 years) were treated with radiotherapy (60 Gy) or enrolled in a Fractionated Stereotactic Conformal-Radiotherapy Phase II trial (69.4 Gy). Concomitant and adjuvant chemotherapy with Temozolomide (TMZ) was administered. Charlson Index Co-morbidity (CCI) was used to assess co-morbidity. Toxicity was evaluated according to RTOG score. Survival analysis was performed by the Kaplan-Maier. Influence of age and co-morbidity was evaluated using log-rank test. From 2001 to 2008, 146 patients were enrolled: 56 (38.4 %) aged over 65 and 90 under 65. CCI ≥ 1 was observed in 41 % of elderly and 22 % of young group. Patients' compliance was 97.9 % for radio-chemotherapy. Acute toxicity was mild with no difference between the groups. Global median progression-free survival (PFS) and overall survival (OS) were 12 and 18 months, respectively. Age, surgery and radiation dose correlated with survival (p = 0.01, p = 0.04 and p = 0.03). CCI ≤ 2 did not show any influence on OS. Our data show that elderly with a good performance status and few co-morbidity may be treated as younger patients; moreover, age confirms a negative impact on survival while CCI ≤ 2 did not correlated with OS.

Medulloblastoma (MB) occurs infrequently in adult patients and standard treatment is still controversial. We report our long-term, single-institution experience of adult MB and a review of the literature. We analysed adult patients with histologically proved MB treated by postoperative radiotherapy. Primary endpoints were local control (LC), disease-free survival (DFS), and overall survival (OS). Acute toxicity was reported according to CTC-NCI score vers. 3.0 and specific neuropsychological assessment analysis was performed to define late brain toxicity. From 1990-2008, 13 patients were treated by craniospinal (CSI, 12/13) or cranial irradiation (1/13, because of bad clinical conditions). Median follow up was 101 months (64-218). Complete radiological response was observed in 12/13 patients and a partial response in 1/13. Ten-year LC, OS, and DFS were 91, 76, and 84%, respectively. Two patients died because of local and spinal progression after 13 and 62 months. Acute G3 haematological toxicity (RTOG score) was observed for one patient only. The neuropsychological analysis did not reveal late toxicity related to brain radiotherapy. This experience confirms the efficacy and safety of radiotherapy in adult MB patients, resulting in very interesting 10-year LC and OS.

We explored the feasibility of concurrent palliative chemotherapy and low-dose fractionated radiotherapy (LD-FRT) in glioblastoma multiforme (GBM). Patients with recurrent/progressive GBM at least 3 months after the end of primary radiotherapy received 0.3 Gy twice daily with cisplatin and fotemustine if progressing on temozolomide, or 0.4 Gy twice daily with temozolomide if recurrent 4-6 months later (retreatment group). Newly diagnosed GBM with gross residual mass received 30 Gy with concomitant and adjuvant temozolomide and 0.4 Gy twice daily from the second adjuvant cycle (naive group) for 2-4 cycles. Twenty-six patients were enrolled. In the retreatment group (n = 17; median LD-FRT total dose 7.2 Gy [range 2.4-11.6]), grade 3 or 4 hematological toxicity was observed in 5.9% of patients. Median follow-up time was 20 months (range 4-35). Median progression-free survival (PFS) and overall survival (OS) from the time of recurrence or progression were 4 and 8 months, respectively (OS at 6 months, 69%; at 12 months, 16.7%). In the naive group (n = 9; median LD-FRT total dose 8 Gy [range 3.2-16]), grade 3 or 4 hematological toxicity was observed in 11.1% of patients. Median follow-up time was 17 months (range 8-20)-median PFS was 9 months, with PFS at 6 months and at 1 year of 66.7% and 26.7%, respectively; and median OS was 12 months, with OS at 6 months and at 1 year of 77.8% and 34.6%, respectively. LD-FRT with concurrent chemotherapy was well tolerated.

Background: Spermatic cord sarcomas are rare. The therapeutic approach is based only on case reports and small series. The standard treatment is radical orchiectomy with wide local resection, while the role of adjuvant therapies is not clear. We present a case of fibrosarcoma of the spermatic cord treated with surgery and adjuvant radiotherapy. A review of the literature about the role of adjuvant treatments is also discussed., Case Report: A 59-year-old man presented a right testicular mass of about 4 × 3 cm in size. Biopsy showed a high-grade polymorphous sarcoma, consistent with a diagnosis of poorly differentiated fibromyosarcoma. He underwent a right radical inguinal orchiectomy and adjuvant radiotherapy (total dose: 5940 cGy). During treatment the patient developed a G3 skin toxicity (RTOG score) in the inguinal fold. After a follow-up of 57 months, he is alive and without evidence of local or distant recurrence. No late toxicity was noted., Conclusion: The optimal adjuvant management of spermatic cord sarcoma is still uncertain. Looking at the literature, it seems that adjuvant radiotherapy can improve locoregional control and disease-free survival without additional late toxicity.

Objective: To verify whether the treatment of brain oligometastases with whole-brain radiotherapy (WBRT) plus stereotactic radiotherapy (SRT) or surgical resection results in different outcomes., Methods: Files of patients affected by brain metastases submitted to surgical resection followed by WBRT (group A) or WBRT + SRT (group B) were retrospectively selected for this study. The two treatment groups were matched for the following potential prognostic factors: WBRT schedule, age, gender, performance status, tumor type, number of brain metastases, extra-cerebral metastases, and recursive partitioning analysis class (RPA). The outcomes of patients in both groups were evaluated in terms of toxicity, local control, and overall survival., Results: Total of 97 patients were selected (56 male; 42 female) who were respectively submitted to surgical resection followed by WBRT (group A, n = 50 patients) or WBRT + SRT (Group B, n = 47 patients). Median follow-up was 95 months (range, 8-171 months). The 1-year local control rates were 46.0% and 69.0% respectively. No significant difference in local tumor control was observed between group A and B (p = 0.10). Median overall survival was 15 and 19 months in group A and B, respectively. One-year survival was 56.0% and 62%, respectively. No difference was observed in the two groups (p = 0.40)., Conclusion: Surgery remains the main therapeutic approach in symptomatic patients; nevertheless, our data support the use of WBRT plus SRT in one or two brain metastases smaller than 3 cm.

Purpose: To evaluate the impact of radiotherapy on pain relief and on recalcification in patients with osteolytic lesions due to plasma cell neoplasm., Patients and Methods: Pain relief was evaluated according to a 0-10 verbal numerical rating scale (NRS) and recalcification was measured using radiological imaging., Results: From 1996-2007, 52 patients were treated (Table 1). Median total dose was 38 Gy (range, 16-50 Gy). Pain be-fore radiotherapy was reported by 45 of 52 (86.5%) patients (Table 2) as being severe (8 ≤ NRS ≤ 10) in 5 (11%), moderate (5 ≤ NRS ≤ 7) in 27 (60%), and mild in 13 (29%). Pain relief was achieved in 41 of 45 patients (91%): complete relief was obtained in 21 (51.2%) and partial relief in 20 patients (48.8%); patients with severe pain experienced resolution and none present-ed an increase of pain. Drugs reduction/suspension was achieved in 7 of the 21 patients with complete response. Of 42 patients evaluable for recalcification (Table 3), 21 (50%) presented a radiological response, which was identified as complete in 16 (38%)., Conclusion: Our data confirm the effectiveness of radiotherapy for pain relief, including a reduction in drug intake, and on recalcification, thus, supporting its use in a multidisciplinary approach.

Purpose: To assess survival, local control and toxicity using fractionated stereotactic conformal radiotherapy (FSCRT) boost and temozolomide in high-grade gliomas (HGGs)., Patients and Methods: Patients affected by HGG, with a CTV(1)(clinical target volume, representing tumor bed ± residual tumor + a margin of 5 mm) ≤ 8 cm were enrolled into this phase II study. Radiotherapy (RT, total dose 6,940 cGy) was administered using a combination of two different techniques: three-dimensional conformal radiotherapy (3D-CRT, to achieve a dose of 5,040 or 5,940 cGy) and FSCRT boost (19 or 10 Gy) tailored by CTV(1)diameter (≤ 6 cm and > 6 cm, respectively). Temozolomide (75 mg/m(2)) was administered during the first 2 or 4 weeks of RT. After the end of RT, temozolomide (150-200 mg/m(2)) was administered for at least six cycles. The sample size of 41 patients was assessed by the single proportion-powered analysis., Results: 41 patients (36 with glioblastoma multiforme [GBM] and five with anaplastic astrocytoma [AA]) were enrolled; RTOG neurological toxicities G1-2 and G3 were 12% and 3%, respectively. Two cases of radionecrosis were observed. At a median follow-up of 44 months (range 6-56 months), global and GBM median overall survival (OS) were 30 and 28 months. The 2-year survival rate was significantly better compared to the standard treatment (63% vs. 26.5%; p < 0.00001). Median progression-free survival (PFS) was 11 months, in GBM patients 10 months., Conclusion: FSCRT boost plus temozolomide is well tolerated and seems to increase survival compared to the standard treatment in patients with HGG.

Aims and Background: Merkel cell carcinoma (MCC) is a rare skin tumor occurring mostly in older people. Postoperative radiotherapy is strongly recommended to improve local control. A case of a MCC treated by radiotherapy associated with imiquimod (Aldara) is presented. A possible physiopathological rationale for this concomitant treatment is also given., Materials and Methods: We treated a diabetic 82-year-old man presenting with a MCC of the right zygomatic area. Despite surgery, postoperative ultrasonography showed a firm, painless residual mass of about 11 x 10 cm, fixed to the deep tissues. Parotid and zygomatic areas were treated along with the ipsilateral laterocervical lymph nodes. The total dose to the planning target volume was 50.4 Gy (1.8 Gy/day). Imiquimod was applied once a day to the zygomatic area with macroscopic infiltration and to the surrounding erythema., Results: During the combination treatment, the patient showed acute G3 skin toxicity (RTOG) and a scab that resolved after a 3-week interruption of the radiotherapy and imiquimod treatment. When the scab was removed, the underlying skin appeared completely re-epithelialized. Imiquimod was suspended and treatment was continued only with irradiation. During this second phase of the treatment, the patient developed G2 dermatitis and G2 stomatitis. Clinical and instrumental re-evaluation showed a complete response 7 months after the end of radiotherapy, with very good local tropism., Conclusion: This case report suggests the possible effective use of immunomodulators, in this case imiquimod, combined with radiation therapy for cutaneous malignancies such as MCC. Skin tolerance should be an important issue to consider.

We tested the efficacy and safety of temozolomide (TMZ) when given concomitantly to radiotherapy only in the first and last weeks of treatment to patients affected by high grade gliomas. Conformal radiotherapy (CTV1: tumor bed + residual tumor if present + 1.5 cm, 5,940 cGy, 180 cGy/day; CTV2: oedema, 3,960 cGy, 180 cGy/day) was associated with TMZ, 75 mg/m(2) x 5 days, the first and last weeks of radiotherapy. Adjuvant chemotherapy with TMZ (150 mg/mq daily x 5 days, q28 on the first cycle, 200 mg/mq daily x 5 days, q28 for the following cycles) was given, after chemoradiation, until disease progression or up to 6 cycles. From October 2000 to December 2003, 29 patients (25 GBL, 86.2%; 4 AA, 13.8%) were enrolled in this study. Twenty-two patients (75.8%) received a median 6 cycles of adjuvant chemotherapy with TMZ (range 1-20). Hematological toxicity was absent during concomitant chemoradiation and mild in adjuvant therapy, while neurological toxicity (seizures) was observed only in one case. At a median follow-up of 66 months (range 3-96), median progression-free survival (PFS) was 8 months, with a 1- and 2-year PFS of 46.7 and 28.7%, respectively; median overall survival (OS) time was 21 months, with a 1- and 2-year OS of 69.2 and 42.3%, respectively. In our experience, TMZ proved to be effective even when given only during the first and the last week of radiotherapy, with lower hematological toxicity.

Chemotherapy including high-dose methotrexate (HD-MTX), with or without radiotherapy, is standard treatment for primary central nervous system lymphoma (PCNSL). It remains controversial whether addition of other drugs will add to therapeutic efficacy. We report here on 41 patients with PCNSL treated using a combined treatment modality, including HD-MTX (3.5 g/m(2) for 2 cycles) prior to whole brain radiotherapy (WBRT). In 22 patients, the chemotherapy was intensified by adding high-dose cytosine arabinoside (HD-AraC) (2g/m(2) for 4 doses for 2 cycles). Complete remission at the end of the combined treatment was obtained in 23 of 34 assessable patients (67%), and the predicted 5-year overall and disease-free survival rates were 24% and 46%, respectively, without differences between treatment groups. The addition of HD-AraC was complicated by severe infections in 17/22 (77%) patients, resulting in 3 toxic deaths. Our study indicates that addition of HD-AraC may not improve clinical outcome in PCNSL, while it increases toxicity. More targeted and less toxic therapies are warranted.

Background: Local recurrence is one of the most important problems related to resection of rectal cancer in locally advanced cases (T3-T4). Total mesorectal excision (TME) is the mainstay of surgical therapy, although many articles have been published about the availability of intraoperative radiotherapy (IORT) for the control of locally advanced rectal cancers., Methods: The authors describe six patients affected by advanced rectal cancer (T3N1) whom they treated with neoadjuvant radiochemotherapy and laparoscopic rectal resection combined with TME and IORT., Results: The operative time did not exceed 6 h in any case with IORT treatment. The procedure itself and the transfer of patients to the radiotherapy room accounted for about 2 h. The postoperative course was uneventful in every case, and all the patients were discharged within the first 8 postoperative days., Conclusions: This report describes the technical aspect and the feasibility of IORT associated with laparoscopic surgical resection for rectal cancer.

Based on the successful results achieved in survival and local control with radiotherapy of prostate cancer recent studies tried to establish some models to reliably predict late rectal toxicity. In fact, the rectum, due to its location, represents an organ at risk of acute and late toxicity with the onset of acute or chronic radiation proctitis. The concept of late consequential effect has gained ground. It implies that the late damage might be a direct consequence of the acute damage. Dose-escalation studies, conformal radiotherapy (3D-CRT) and intensity modulated radiotherapy (IMRT) led to the identification of parameters, based on dose-volume histograms (DVH), able to separate patients at low and high risk of toxicity. Precise predictive dosimetric factors play a major role in the definition of the onset of toxicity. The monitoring system of late toxicity used by the authors is presented.

There is a relationship between a given radiation dose and the resulting biological effect in the management of head and neck cancer. Radiation mucositis represents a frequent complication in cancer chemoradiation. Its prevention and treatment are major goals in radiation therapy schedules. Critical tissues can be spared using high conformal radiation therapy (3DCRT) based on consensus guidelines for target volume. Current approaches to radiation mucositis with respect to the dose and volume impact are illustrated. The monitoring system of late toxicity used by the authors is presented.

The combination of radiotherapy with chemotherapy is now considered the standard treatment for a number of tumors. However frequently, within radiotherapy as well as medical oncology, considerable skepticism has been expressed about the real impact of this therapeutic modality, in spite of the improvement in terms of outcome seen in numerous trials concerning head and neck, lung, esophageal cancer and tumors of the anal canal, the uterine cervix and pancreas. Considering the evident clinical advantages achieved in the last 2-3 decades, a close collaboration between basic, preclinical and clinical research is desirable to further optimize the outcomes based on the present radiobiological knowledge. As for the preclinical evaluation different methods should be concomitantly used to analyze the pharmacokinetics and mechanism of action; the method of tumor growth delay should be used especially in neoadjuvant clinical settings; the method of tumor control should be used when chemoradiation is aimed at the local cure of the patient independently of subsequent surgery.

Pain control in patients with cancer represents a significant aspect of radiation therapy practice. Radiation therapy is one of the most effective, and often the only, therapeutic option to relieve pain caused by nerve compression or infiltration by malignant tumor, pain from liver and bony metastases and it provides also successful palliation of dysphagia caused by oesophageal carcinoma and of pain due to pancreatic cancer. Various instruments are avaliable for pain evaluation but a valid methodology to assess the pain status in the patient with cronic cancer pain is still an important clinical problem. In this complex and wide scene this contribution wants to confirm the role of radiotherapy in cancer pain control, in paricular in bone metastases, and to involve the patient himself in the survey of radiation treatement response by a subjective evaluation of bone pain, elaborating a reliable and valid unidimensional method by which recording the self-rating of the patient's sensation. Materials and Methods For the subjective evaluation of pain caused by bone metastases we used an application form with which drawing information in the course of time in terms of: response to the treatment, duration of symptom relief and quality of life. Results Considering as cut-off a dose of 30 Gy, which is commonly considered the conventional treatment for bone metastases, the partial and complete response were, respectively, of 54% and 30% in the patients treated with dose higher than or equal to 30 Gy, and 60% and 20% in the ones treated with doses lower than 30 Gy. In the whole, in 84 patients, the global response was of 82%, in accordance with literature. Conclusion In this retrospective study, the analysis of patient's subjective experience confirmed the effectiveness of radiotherapy in reducing pain caused by bone metastases and in improving quality of life of the patient himself. Given the conflicting opinions on low-dose short-course radiotherapy versus prolonged or higher dose schedules on initial pain relief, we are going to define categories of homogenous patients on whom starting treatment schedules with the aim or of palliation of the symptom or of the functional restitutio, on the base of the expectation and the quality of life.

The organizational optimization in radiotherapy tends to a correct balance of quality of service and containment of health care expenditure; this goal is necessarily correlated with the real potentialities available to each center while considering the possible clinical benefits for the patient. In lung cancer, outcomes achieved with radiation therapy are encouraging in terms of local control and survival when treatment is performed with the available modern technology whose costs from an exclusively economic analysis are shown to be still quite high. In an assessment focused on clinical outcomes, better local control, higher survival and improved quality of life represent tangible benefits: this has a positive impact on community costs and may represent a high priority goal for health care providers, yielding a benefit that can be quantified with the most recent analyses of health care economy.

Concomitant radiochemotherapy is the standard treatment of squamous cell carcinoma of the anal canal. It can afford a high local control rate though the same impact has not been observed on survival. A few reports have concerned the impact of local control on distant metastases and survival. From 1988 to 1998 at the "Divisione di Radioterapia" of the "Università Cattolica del S. Cuore" of Rome 30 patients with squamous cell carcinoma of the anal canal were treated for cure. Treatment consisted of two cycles of radiotherapy (23.4 Gy) with a 4-5 week split in each cycle. 5FU (100 mg/sqm/24 h) was administered in continuous infusion for the first 4 days of therapy; mitomycin C (10 mg/sqm bolus) was administered on day 1, 4-6 weeks after the end of cycle 2 of concomitant radiochemotherapy, patients received a boost of interstitial brachytherapy. Local control on T of all patients was 84% at 5 years. Six patients showed locoregional recurrence: 3 recurrences on T and 4 disease progressions in locoregional lymph nodes. 3 of 6 patients underwent salvage surgery. The initial extent of the disease, the patient's age and brachytherapy boost did not have a statistically significant influence on local control. Two of the 30 patients showed liver metastases, and at their appearance, one patient was free of local disease while the other showed locoregional progression after Miles' operation for salvage. The metastasis-free interval was not significantly influenced by local control, although at 5 years, 96% of patients with local control of T were free of metastases vs 75% of those with recurrence on T (p = 0.22). Overall actuarial survival at 5 years was 75%. The behavior of survival in our experience seemed to be significantly influenced by local control: in the group with local control, 5-year survival was 85% vs 40% of patients with local recurrence (p = 0.01).