Impact of different setup approaches in image-guided radiotherapy as primary treatment for prostate cancer: a study of 2940 setup deviations in 980 MVCTs.

AIM: The goal of this study was to assess the impact of different setup approaches in image-guided radiotherapy (IMRT) of the prostatic gland. METHODS: In all, 28 patients with prostate cancer were enrolled in this study. After the placement of an endorectal balloon, the planning target volume (PTV) was treated to a dose of 70 Gy in 35 fractions. A simultaneously integrated boost (SIB) of 76 Gy (2.17 Gy per fraction and per day) was delivered to a smaller target volume. All patients underwent daily prostate-aligned IGRT by megavoltage CT (MVCT). Retrospectively, three different setup approaches were evaluated by comparison to the prostate alignment: setup by skin alignment, endorectal balloon alignment, and automatic registration by bones. RESULTS: A total of 2,940 setup deviations were analyzed in 980 fractions. Compared to prostate alignment, skin mark alignment was associated with substantial displacements, which were ≥ 8 mm in 13%, 5%, and 44% of all fractions in the lateral, longitudinal, and vertical directions, respectively. Endorectal balloon alignment yielded displacements ≥ 8 mm in 3%, 19%, and 1% of all setups; and ≥ 3 mm in 27%, 58%, and 18% of all fractions, respectively. For bone matching, the values were 1%, 1%, and 2% and 3%, 11%, and 34%, respectively. CONCLUSION: For prostate radiotherapy, setup by skin marks alone is inappropriate for patient positioning due to the fact that, during almost half of the fractions, parts of the prostate would not be targeted successfully with an 8-mm safety margin. Bone matching performs better but not sufficiently for safety margins ≤ 3 mm. Endorectal balloon matching can be combined with bone alignment to increase accuracy in the vertical direction when prostate-based setup is not available. Daily prostate alignment remains the gold standard for high-precision radiotherapy with small safety margins.

Callous-Unemotional Traits and Intelligence in Children with Externalizing Behavioral Problems.

Research on the association between callous-unemotional (CU) traits and intelligence yielded contradictory results. Moreover, several previous studies focused on global intelligence scores or verbal vs. nonverbal/performance abilities usually evaluated with short/abbreviated instruments. The current study builds on these previous works and explores the link between CU traits and intelligence using the full version of the Wechsler Intelligence Scale for Children-4th Edition (WISC-IV), which provides four different verbal and nonverbal abilities scores. This guarantees a more detailed evaluation of children's intelligence and its relation to CU traits. The sample included children (N = 149; age 6-14 years old) with severe behavioral problems. Clinicians administered the WISC-IV, and parents completed questionnaires evaluating the child's externalizing problems and CU traits. Findings showed that CU traits were associated with lower verbal comprehension scores after also controlling for gender, age, externalizing problems, and the other WISC-IV indexes. In addition, CU traits and externalizing problems did not interact in predicting the WISC-IV indexes, and there were no significant differences in the WISC-IV indexes between children with CU traits and high vs. low externalizing problems. The current study suggests the relevance of assessing and addressing verbal abilities in children with behavioral problems and CU traits.

Postoperative radiotherapy in stage I/II endometrial cancer: retrospective analysis of 883 patients treated at the University of Florence.

INTRODUCTION: The efficacy of postoperative radiotherapy (RT) in the treatment of early-stage endometrial carcinoma (EC) is still under debate. This study was aimed to review the outcome and adverse effects in patients treated for EC with postoperative RT at a single center. METHODS: A total of 883 patients with pathological stages I to II EC were retrospectively analyzed. Surgery consisted of total abdominal hysterectomy and bilateral salpingo-oophorectomy, or vaginal hysteroannessiectomy in 532 patients (60.2%) with pelvic lymphadenectomy in 351 patients (39.8%). Seven hundred forty-seven patients (84.6%) underwent whole pelvic RT (WPRT) and 136 (15.4%) combined WPRT and vaginal brachytherapy (BT) boost. RESULTS: At a median follow-up of 9 years (range, 1.2-27.6 years), we observed 10.6% disease relapse. Forty-seven patients experienced local recurrence (LR), and 38 patients experienced distant metastases (DMs). At univariate analysis, age at diagnosis (P < 0.0001), stage (P < 0.04), and histological subtype (P < 0.0001) resulted in significant prognostic factors. At multivariate analysis, histotype emerged as an independent relapse predictor (P = 0.0001). Acute WPRT-related toxicity was mild; diarrhea was the most common adverse effect (19.8%). We recorded long-term adverse effects in 7.8% of the patients. CONCLUSIONS: Our study showed that patients with early-stage EC have a good outcome in overall survival and disease-free survival. In our experience, standard surgery (including hysterectomy and bilateral salpingo-oophorectomy followed by WPRT with or without BT) showed an acceptable toxicity profile.

Adjuvant whole pelvic radiotherapy in 43 patients with uterine serous cancer: outcome and patterns of failure.

AIMS AND BACKGROUND: Uterine serous cancer is associated with a poor outcome and poses a therapeutic challenge. We retrospectively evaluated the experience of the Radiotherapy Department of the University of Florence. METHODS: Forty-three patients with stage I-III uterine serous cancer underwent surgery with (18 patients, group 1) or without complete surgical staging (25 patients, group 2) followed by adjuvant whole pelvic radiotherapy alone or combined with vaginal brachytherapy (in 35 and 8 cases, respectively). The median dose delivered with whole pelvic radiotherapy was 50 Gy (range, 45-56) and for brachytherapy was 20 Gy (range, 20-30). RESULTS: Actuarial overall survival and disease-free survival rates at 5 years were 62.5% and 61%, respectively. Local failure was observed in 17 patients (39.5%) and distant metastasis in 10 (23.2%). Nine patients had both local failure and distant metastasis, which had developed concurrently in 7 cases. Isolated abdominal failure occurred in 4 cases (9.3%). Local relapse was noted in 22.2% of patients in group 1 compared to 52% in group 2. A trend towards a better 5-year overall survival (67.2% vs 58%), disease-free survival (63% vs 59%) and local control (70% vs 59%) was observed in group 1 than group 2, although the difference between the two groups failed to reach statistical significance. CONCLUSIONS: Given the patterns of failure of patients with uterine serous cancer, adjuvant whole pelvic radiotherapy may be a reasonable approach, although novel integrated strategies are needed because the results achieved remain disappointing. Adjuvant whole pelvic radiotherapy might improve overall survival, disease-free survival and local control in complete surgically staged patients, but further investigations are required.

Cetuximab and Radiation Therapy Versus Cisplatin and Radiation Therapy for Locally Advanced Head and Neck Cancer: Long-Term Survival and Toxicity Outcomes of a Randomized Phase 2 Trial.

PURPOSE: This study describes the long-term survival and toxicity outcomes of a multicenter randomized phase 2 trial comparing radiation therapy (RT) plus cisplatin (CDDP) or cetuximab (CTX) as first line treatment in locally advanced head and neck cancer (LASCCHN). METHODS AND MATERIALS: Between January 2011 and August 2014, 70 patients were enrolled and randomized to receive RT plus weekly CDDP (40 mg/m2) or CTX (250 mg/m2 plus a loading dose of 400 mg/m2). This updated series focuses on late toxicities (graded by using Common Terminology Criteria for Adverse Events version 4.0) and long-term survival outcomes in terms of local control, overall survival, cancer-specific survival, and metastasis-free survival (MFS). A supplementary analysis based on human papilloma virus (HPV) status was also performed. RESULTS: No statistically significant difference was found in terms of late effects (xerostomia, fibrosis, mucosal atrophy, weight loss). In the CDDP arm and the CTX arm, 5-year local control rates were 67% and 48%; 5-year MFS rates were 83% and 97%; 5-year overall survival rates were 61% and 52%; and 5-year cancer-specific survival rates were 70% and 59%, respectively. None of these differences reached statistical significance. A subgroup analysis by HPV status and anatomic subsites revealed that in HPV+ oropharyngeal carcinoma, better survival was obtained in the CDDP arm (although statistical tests were not performed owing to the small sample size). Conversely, no statistically significant differences were observed in HPV- oropharyngeal carcinoma and other anatomic subsites, except for the confirmed better MFS rates of the CTX arm. CONCLUSIONS: Long-term results are in line with current literature suggesting that RT + CTX is inferior to RT + CDDP for the definitive treatment of LASCCHN. However, if not as an alternative to CDDP, CTX might still play a role in LASCCHN, particularly in HPV- cases.

Non-pegylated liposomal doxorubicin in combination with cyclophosphamide or docetaxel as first-line therapy in metastatic breast cancer: a retrospective analysis.

AIMS AND BACKGROUND: Anthracyclines such as doxorubicin play a central role in the management of advanced breast cancer. Unfortunately, the clinical benefits of anthracyclines are limited by cardiotoxicity that can lead to the development of potentially fatal congestive heart failure. In order to limit anthracycline-related cardiotoxicity, liposomal formulations of doxorubicin have been developed. This retrospective analysis evaluated the experience obtained with non-pegylated liposomal doxorubicin as first-line therapy in 34 patients with metastatic breast cancer. METHODS: Patients received non-pegylated liposomal doxorubicin in combination with either cyclophosphamide (n = 14) or docetaxel (n = 20) for up to eight cycles, and efficacy and safety were assessed according to standard criteria. RESULTS: The overall response rate was 71%. The median progression-free survival was 8 months in patients receiving non-pegylated liposomal doxorubicin plus cyclophosphamide and 13.8 months in those receiving non-pegylated liposomal doxorubicin plus docetaxel (P = 0.2). The most commonly observed toxicities were grade 1-2 leucopenia, alopecia, nausea and vomiting; no grade 3-4 toxicities were observed. Overall, three patients (9%) experienced grade 1 cardiac toxicity. CONCLUSIONS: Our results support the use of non-pegylated liposomal doxorubicin as an alternative to conventional doxorubicin formulations in combination regimens for the first-line therapy of metastatic breast cancer.

Concurrent cyclophosphamide, methotrexate, and 5-fluorouracil chemotherapy and radiotherapy for early breast carcinoma.

PURPOSE: The optimal sequencing of adjuvant chemotherapy (CT) and radiation therapy (RT) in patients with early-stage breast cancer remains unclear. PATIENTS AND METHODS: We retrospectively compared 485 patients treated with conservative breast surgery and postoperative whole-breast RT and six courses of CMF (cyclophosphamide 600 mg/m(2), methotrexate 40 mg/m(2), and 5-fluorouracil 600 mg/m(2)) with 300 patients who received postoperative CMF only and with 509 patients treated with postoperative whole-breast RT only. The mean radiation dose delivered was 50 Gy (range, 46-52 Gy) with standard fractionation. The boost dose was 6-16 Gy according to resection margins and at the discretion of the radiation oncologist. Acute and late RT toxicity were scored using respectively the Radiation Therapy Oncology Group and the Late Effects in Normal Tissues Subjective, Objective, Management and Analytic scale. RESULTS: A slightly higher Grade 2 acute skin toxicity was recorded in the concurrent group (21.2% vs. 11.2% of the RT only group, p < 0.0001). RT was interrupted more frequently in the CMF/RT group respective to the RT group (8.5% vs. 4.1%; p = 0.006). There was no difference in late toxicity between the two groups. All patients in the concurrent group successfully received the planned dose of RT and CT. Local recurrence rate was 7.6% in CT/RT group and 9.8% in RT group; this difference was not statistically significant at univariate analysis (log-rank test p = 0.98). However, at multivariate analysis adjusted also for pathological tumor, pathological nodes, and age, the CT/RT group showed a statistically lower rate of local recurrence (p = 0.04). CONCLUSIONS: Whole-breast RT and concurrent CMF are a safe adjuvant treatment in terms of toxicity.

Cetuximab and Radiotherapy Versus Cisplatin and Radiotherapy for Locally Advanced Head and Neck Cancer: A Randomized Phase II Trial.

PURPOSE: No randomized trials have been conducted to directly compare radiotherapy (RT) with concomitant cisplatin (CDDP) versus concomitant cetuximab (CTX) as first-line treatment of locally advanced squamous cell carcinoma of the head and neck. In this randomized trial, we compared these two treatment regimens in terms of compliance, toxicity, and efficacy. PATIENTS AND METHODS: Eligible patients were randomly assigned in a 1:1 ratio to receive either CDDP 40 mg/m(2) once per week or CTX 400 mg/m(2) as loading dose followed by CTX 250 mg/m(2) once per week concomitant to radical RT. For primary end points, compliance to treatment was defined as number of days of treatment discontinuation and drug dosage reduction. The acute toxicity rate was defined according to the National Cancer Institute Common Toxicity Criteria. Efficacy end points were local recurrence-free survival, metastasis-free survival, cancer-specific survival, and overall survival. RESULTS: The study was discontinued early because of slow accrual after the enrollment of 70 patients. RT discontinuation for more than 10 days occurred in 13% of patients given CTX and 0% given CDDP (P = .05). Drug dosage reduction occurred in 34% given CTX and 53% given CDDP (difference not significant). Toxicity profiles differed between the two arms, with hematologic, renal, and GI toxicities more frequent in the CDDP arm, and cutaneous toxicity and the need for nutritional support more frequent in the CTX arm. Serious adverse events related to treatment, including four versus one toxic deaths, were higher in the CTX arm (19% v 3%, P = .044). Locoregional control, patterns of failure, and survivals were similar between the treatment arms. CONCLUSION: CTX concomitant to RT lowered compliance and increased acute toxicity rates. Efficacy outcomes were similar in both arms. These results raise the issue of appropriately selecting patients with head and neck cancer who can benefit from CTX in combination with RT.

Management of inflammatory breast cancer: focus on radiotherapy with an evidence-based approach.

Inflammatory breast cancer represents a rare and extremely aggressive subtype of breast cancer. Due to its rarity, prospective studies are a difficult goal to obtain in this field. Nowadays a multimodal approach seems to be the standard approach. Role and timing of surgery, radiotherapy and chemotherapy are still debated issues. In this scenario interest is rising in molecular and target therapies. We performed a review analyzing the management of this unfavorable disease focusing on the role of radiotherapy, with particular emphasis on levels of evidence.

Radiotherapy timing in 4,820 patients with breast cancer: university of florence experience.

PURPOSE: To analyze the relationship between a delay in radiotherapy (RT) after breast-conserving surgery and ipsilateral breast recurrence (BR). METHODS AND MATERIALS: We included in our analysis 4,820 breast cancer patients who had undergone postoperative RT at the University of Florence. The patients were categorized into four groups according to the interval between surgery and RT (T1, <60 days; T2, 61-120 days; T3, 121-180 days; and T4, >180 days). RESULTS: On multivariate analysis, the timing of RT did not reach statistical significance in patients who received only postoperative RT (n = 1,935) or RT and hormonal therapy (HT) (n = 1,684) or RT, chemotherapy (CHT), and HT (n = 529). In the postoperative RT-only group, age at presentation, surgical margin status, and a boost to the tumor bed were independent prognostic factors for BR. In the RT plus HT group, age at presentation and boost emerged as independent prognostic factors for BR (p = 0.006 and p = 0.049, respectively). Finally, in the RT, CHT, and HT group, only multifocality was an independent BR predictor (p = 0.01). Only in the group of patients treated with RT and CHT (n = 672) did multivariate analysis with stepwise selection show RT timing as an independent prognostic factor (hazard ratio, 1.59; 95% confidence interval, 1.01-2.52; p = 0.045). Analyzing this group of patients, we found that most patients included had worse prognostic factors and had received CHT consisting of cyclophosphamide, methotrexate, and 5-fluorouracil before undergoing RT. CONCLUSION: The results of our study have shown that the timing of RT itself does not affect local recurrence, which is mainly related to prognostic factors. Thus, the "waiting list" should be thought of as a "programming list," with patients scheduled for RT according to their prognostic factors.