Coping with modesty during radiotherapy for breast cancer: a multicentric study.

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.

Palliative radiotherapy indications during the COVID-19 pandemic and in future complex logistic settings: the NORMALITY model.

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.

Chemoradiotherapy with temozolomide after high-dose methotrexate for primary CNS lymphoma: a multicenter phase I study of a response-adapted strategy.

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/m2) was followed by concomitant RT and escalating TMZ (50-60-75 mg/m2/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/m2/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/m2/day when administered concomitantly with radiotherapy and after HD-MTX.

Identification of the most significant magnetic resonance imaging (MRI) radiomic features in oncological patients with vertebral bone marrow metastatic disease: a feasibility study.

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.

High-tailored Anal Canal Radiotherapy (HIT-ART): Outcomes of a 10-Year Single Center Clinical Experience.

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.

Ventricular tachycardia ablation through radiation therapy (VT-ART) consortium: Concept description of an observational multicentric trial via matched pair analysis.

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).

Prognostic Score in Radiotherapy Practice for Palliative Treatments (PROPHET) Study for Bone Metastases: An Investigation Into the Clinical Effect on Treatment Prescription.

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.

The Role of Simultaneous Integrated Boost in Locally Advanced Rectal Cancer Patients with Positive Lateral Pelvic Lymph Nodes.

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.

Modern Management of Esophageal Cancer: Radio-Oncology in Neoadjuvancy, Adjuvancy and Palliation.

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.

Immunotherapy and radiotherapy in melanoma: a multidisciplinary comprehensive review.

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.

External validation of a composite bio-humoral index in anal cancer patients undergoing concurrent chemoradiation.

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.

Impact of radiotherapy on pain relief and recalcification in plasma cell neoplasms: long-term experience.

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.

Whole-brain radiotherapy combined with surgery or stereotactic radiotherapy in patients with brain oligometastases: long-term analysis.

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.

Magnetic resonance-guided radiotherapy feasibility in elderly cancer patients: proposal of the MASTER scoring system.

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.

Radiotherapy with Intensity-Modulated (IMRT) Techniques in the Treatment of Anal Carcinoma (RAINSTORM): A Multicenter Study on Behalf of AIRO (Italian Association of Radiotherapy and Clinical Oncology) Gastrointestinal Study Group.

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.

Single-arm phase II study of conformal radiation therapy and temozolomide plus fractionated stereotactic conformal boost in high-grade gliomas: final report.

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.

Radiotherapy and concomitant temozolomide during the first and last weeks in high grade gliomas: long-term analysis of a phase II study.

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.

Treatment of Merkel cell carcinoma with radiotherapy and imiquimod (Aldara): a case report.

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.

Diagnosis and Treatment of Bone Metastases in Breast Cancer: Radiotherapy, Local Approach and Systemic Therapy in a Guide for Clinicians.

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.