Giampaolo Montesi

Recurrences and toxicity after adjuvant vaginal brachytherapy in Stage I–II endometrial cancer: A monoinstitutional experience

PURPOSE To evaluate the incidences of vaginal recurrence and toxicity after vaginal brachytherapy in Stage I-II endometrial cancer. METHODS AND MATERIALS Between 2003 and 2012, 150 high-intermediate-risk Stage I and 7 Stage II patients, median age 64 years, underwent surgery, with or without lymphadenectomy, and 3D brachytherapy: 7 Gy, at 5 mm depth from applicator surface, for 3-week fractions. The effects of age, grading, number of excised lymph nodes and pathologic stage on loco-regional relapse (LRR), metastases, and tumor-related death were investigated. Vaginal toxicity was evaluated during followup visits. RESULTS At 83 months of median followup, 144 patients were disease free, 2 in relapse, 7 deceased from disease, and 4 from other causes. One vaginal (0.6%), five nodal (3.2%), three pelvic over the vaginal cuff (1.9%), and one distant recurrences were seen (0.6%). The 5-year probability of LRR-free, distant metastasis-free and cause-specific survivals for all patients were 93.6% (95% confidence interval [CI]: 88.1-96.7), 97.8% (95% CI: 93.2-99.3), and 96.5% (95% CI: 93.5-99.5) and for Stage I 95.7% (95% CI: 92.2-9.1), 99.3% (95% CI: 98.0-100), and 97.7% (95% CI: 95.2-100), respectively. At multivariate analysis, Stage II disease and more than 12 lymph nodes sampled were associated with LRR (hazard ratio [HR]: 3.88; 95% CI: 1.390-10.878; p = 0.010 and HR: 6.952; 95% CI: 1.591-30.385; p = 0.010) and Stage II with metastasis and tumor-related death (HR: 23.057; 95% CI: 2.296-231.485; p = 0.008 and HR: 4.324; 95% CI: 1.223-15.290; p = 0.023). Vaginal acute and chronic toxicity was 16% and 55.4%, respectively, all only Grades 1-2. CONCLUSIONS For high-to-intermediate-risk Stage I endometrial cancer, 3D vaginal brachytherapy achieved good local control and low toxicity. In Stage II, patients brachytherapy could be administered after complete surgical staging.

Time to surgery and pathologic complete response after neoadjuvant chemoradiation in rectal cancer: A population study on 2094 patients

Highlights • A large population based analysis to evaluate pathologic response according to time of surgery.• LARC patients were treated with modern techniques of radiotherapy and surgery.• The rate of pCR increased according to time interval from 12.6% to 31.1%.• The pCR increasing was 1.5% (about 0.2%/die) per each week of waiting.• Lengthening the interval (>13 weeks) significantly improved the pathological response.

Radiotherapy for early-stage prostate cancer in men under 70 years of age

Aims To demonstrate that radiotherapy (RT) is a valid alternative to surgery in men ≤70 years old with localized prostate cancer. Methods From 1988 to 2009, 214 patients with T1-2 N0 M0 prostate cancer were treated with RT. The effects of patient- and treatment-related risk factors on toxicity were investigated. Results Median follow-up was 105 months (range 14.2-180). The 5-, 10-, and 15-year biochemical relapse-free survival for all 214 patients was 80%, 61.9%, and 57.5%, respectively. In bivariate analysis, age (≤65 vs 65-70 years) was not a significant factor for biochemical relapse, while radiation dose was (p = 0.05) in multivariate analysis. Cancer-specific survival rates at 5, 10, and 15 years were 98.4%, 93.2%, and 69.7%, respectively. Median overall survival (OS) was 167 months (95% confidence interval 147.3-186.7). The OS rates at 5, 10, and 15 years were 91.8%, 75.8%, and 42.5%, respectively. Acute genitourinary (GU) and gastrointestinal (GI) toxicities occurred in 105 (49%) and 98 patients (45.8%), respectively, with only 2 cases of grade III GI toxicity. Late GU and GI toxicities occurred in 17 (7.9%) and 20 (9.3%) patients, respectively, with 1 grade III GI toxicity and 2 grade III GU toxicities. Risk factors for late toxicity were age and RT dose and technique, which were unrelated to acute toxicity. Conclusions Age ≤70 years does not consistently confer a negative prognosis for localized prostate cancer. Radiotherapy appears to be a viable alternative to surgery, offering excellent long-term cancer control.

Epstein-Barr Virus–Positive Mucocutaneous Ulcer Mimicking Rectal Carcinoma at 18F-FDG PET/CT

We report focally intense F-FDG PET/CT rectal activity (SUVmax = 25) with a horseshoe distribution in an 81-year-old man with B-cell chronic lymphocytic leukemia and suspected Richter transformation. While imaging findings were typical for rectal adenocarcinoma, histology revealed Epstein-Barr virus-positive mucocutaneous ulcer.

Policies for reirradiation of recurrent high-grade gliomas: a survey among Italian radiation oncologists

Purpose: To assess the contribution of Italian radiation oncologists in the current management of recurrent high-grade gliomas (HGG), focusing on a reirradiation (reRT) approach. Methods: In 2015, the Reirradiation and the Central Nervous System Study Groups on behalf of the Italian Association of Radiation Oncology (AIRO) proposed a survey. All Italian radiation oncologists were individually invited to complete an online questionnaire regarding their clinical management of recurrent HGG, focusing on a reRT approach. Results: A total of 37 of 210 questionnaires were returned (18% of all centers): 16 (43%) from nonacademic hospitals, 14 (38%) from academic hospitals, 5 (13%) from private institutions, and 2 (6%) from hadron therapy centers. The majority of responding centers (59%) treated ≤5 cases per year. Performance status at the time of recurrence, along with a target diameter <5 cm and an interval from primary radiation ≥6 months, were the prevalent predictive factors considered for reRT. Sixty percent of reirradiated patients had already received a salvage therapy, either chemotherapy (40%) or reoperation (20%). The most common approach for reRT was fractionated stereotactic radiotherapy to a mean (photon) dose of 41.6 Gy. Conclusions: Although there were wide variations in the clinical practice of reRT across the 37 centers, the core activities were reasonably consistent. These findings provide a basis for encouraging a national collaborative study to develop, implement, and monitor the use of reRT in this challenging clinical setting.

Short-course radiotherapy with delayed surgery in unfit locally advanced rectal cancer patients.

Dear Editor: It is well known that preoperative radiotherapy (RT), alone or in combination with chemotherapy (CRT), is the standard of care for patients with locally advanced rectal cancer with both schedules being equivalent in terms of local recurrence and survival. Short-course radiotherapy (SCRT), according to a hypofractionated schedule (25 Gy in 5 fractions), followed by immediate surgery, is extensively used in resectable disease, as it offers the advantages of shorter treatment time, lower costs, and less acute toxicity. On the other hand, it is not recommended when disease down-sizing/down-staging and sphincter saving procedure are required because the interval between the end of RT and surgery is too short for rectal cancer clearance [1]. Changes in intervals between SCRT and surgery were explored both in resectable and unresectable disease. Its feasibility and effectiveness in terms of toxicity and disease downstaging, was demonstrated [2–5], even if short-term survival outcome remains unchanged [5]. From June 2007 to December 2012, 56 locally advanced rectal cancer patients (median age 79 years) who were unfit for chemotherapy due to co-morbidities (median Charlson score 7; range 5–11) and poor Karnofsky Performance Status (KPS) (23 % of cases) underwent SCRT and delayed surgery. The majority of patients (89 %) had tumors in the lower rectum; most were T3 (98 %) and nodes were diseased (N+) in 37 (66 %) patients. 25Gy in 5 fractions, in 5–7 days, were delivered to the primary tumor, and the corresponding mesorectum, with the pathological lymph nodes, plus a 2-cm cranio-caudal margin. Generally, the upper limit of target volume was below S1-S2. RTwas completed in all cases, and no patient developed severe acute toxicity. At a median time of 9 weeks from the end of RT, 46/56 patients (82 %) underwent surgical resection (anterior resection in 72 % and abdominoperineal resection in 28 % of cases); four patients (7 %) refused surgery, and six (11 %) were ineligible because of KPS deterioration. There were no surgery-related deaths. Major pathological response (tumor regression grade—TRG—1–2 according to Mandard score) was observed in 21/46 patients (45 %), with seven (15 %) obtaining pathological complete response (pCR or TRG 1 according to Mandard score). Tumor stage, tumor and node categories, were significantly down-staged compared with the initial radiological assessment, as 88 % of patients did not show node involvement. Our results compared favorable with those published in the literature, both in terms of downstaging and pCR rate [2–5]. In particular, in cohorts with both resectable and unresectable disease, about 70% of patients did not show node involvement, and pCR rates ranged from 8 to 13 % [2–5]. These studies demonstrated that a long interval between SCRT and surgery was a valid alternative to longcourse pre-operative CRT in elderly patients with poor performance status and/or co-morbidities and renewed interest in this approach for younger patients with less advanced disease who are usually treated with concomitant CRT [4, 5]. In our experience, local recurrence (LR) developed in three of the 46 surgical patients (6.5 %) and distant metastases (DM) in eight of all 56 enrolled patients (14 %). These findings compared favorable with those published in the literature [3, 5], even if a wider range of events may occur (LR 0–7 %; DM 2.8–24 %). Surgery and pathological stage adjusted for age, grade, and TRG were significant prognostic factors. In particular, surgery significantly influenced cancer-specific survival (65 vs 47 months) and distant metastases-free * Marco Lupattelli kiralupis@libero.it

Does ultrasound provide any added value in breast contouring for radiotherapy after conserving surgery for cancer

BackgroundWhole breast irradiation after conserving surgery for breast cancer requires precise definition of the target volume. The standard approach uses computed tomography (CT) images. However, since fatty breast and non-breast tissues have similar electronic densities, difficulties in differentiating between them hamper breast volume delineation. To overcome this limitation the breast contour is defined by palpation and then radio-opaque wire is put around it before the CT scan. To optimize assessment of breast margins in the cranial, caudal, medial, lateral and posterior directions, the present study evaluated palpation and CT and determined whether ultrasound (US) provided any added value.MethodsTwenty consecutive patients were enrolled after they had provided informed consent to participating in this prospective study which was approved by the Regional Public Health Ethics Committee. Palpation and US defined breast margins and each contour was marked and outlined with a fine plastic wire. Breasts were then contoured on axial CT images using the breast window width (WW) and window level (WL) (401 and 750 Hounsfield Units –HU- respectively), at which setting the plastic wires were invisible. Then, the lung window function (WW 1601 HU; WL −300 HU) was inserted to visualize the plastic wires which were used as guidelines to contour the palpable and US breast volumes. As each wire had a different diameter, both volumes were easily defined on CT slices. Results were analyzed using descriptive statistics, percentage overlap and reproducibility measures (agreement and reliability).ResultsVolumes: US gave the largest and palpation the smallest. Agreement was best between palpation and CT. Reliability was almost perfect in all correlations. Extensions: Cranial and posterior were highest with US and smallest with palpation. Agreement was best between palpation and CT in all extensions except the cranial. Since strong to almost perfect agreement emerged for all comparisons, reliability was high.ConclusionsUS may be useful in defining the cranial and posterior extensions, mainly when tumours are localized there. This study demonstrates that the now standard radio-opaque wires around the palpable breast may not be needed in breast contouring.

Metachronous cardiac and cerebral sarcomas: case report with focus on molecular findings and review of the literature.

Although multiple primary malignancies are relatively rare, they have increased in frequency over the last decades, partly because of advances in diagnosis and therapy. This report describes for the first time the case of a patient with past occupational exposure to asbestos and no family history of cancer who developed 2 rare primary malignancies: a cardiac sarcoma and a gliosarcoma 11 months later. Molecular-cytogenetic studies did not identify common lesions to these 2 rare metachronous sarcomas. The gliosarcoma was associated with monosomy 10 and underlying PTEN monoallelic loss, which has been recurrently observed. In the cardiac sarcoma, MDM2 amplification and CDKN2AB/9p21 biallelic deletion suggested intimal sarcoma. No causal relationship was found between cardiac sarcoma and asbestos exposure, although MDM2 abnormalities were linked to malignant mesothelioma.

Prostate cancer: contouring target and organs at risk by kilovoltage and megavoltage CT and MRI in patients with and without hip prostheses

OBJECTIVE In radiotherapy treatment, planning target volume and organs at risk are contoured on kilovoltage CT (kVCT) images. Unlike MR images, kVCT does not provide precise information on target volume extension. Since neither kVCT nor MRI may be suitable for contouring in patients with ferrous hip prostheses, this study evaluated whether megavoltage CT (MVCT) reduced interobserver variability. METHODS Two patients without hip prostheses and one patient (Patient 3) with hip prostheses were enrolled. Six radiation oncologists contoured prostate, rectum and bladder on kVCT (Patients 1 and 3), MRI (Patient 2) and MVCT images (Patient 3). MVCT was acquired with fine, normal and coarse modalities. Interobserver variability for each organ was analysed using conformity index (CI) and coefficient of variation (CV). RESULTS In patients without hip prostheses, CIs were higher in prostate contouring with MRI than with kVCT, indicating lower interobserver variability with MRI. Very slight variations were seen in rectum and bladder contouring. In the patient with hip prostheses (Patient 3), contouring on kVCT lowered CI and increased CV in the prostate, bladder and rectum. The differences were more marked in the prostate. Only fine modality MVCT reduced interobserver variability and only for the prostate. CONCLUSION Even though greater noise and less soft-tissue contrast increase contouring variability with MVCT than with kVCT, lack of artefacts on MVCT could provide better image definition by this modality in hip prosthesis patients in whom MRI is precluded. ADVANCES IN KNOWLEDGE We recommend the fine modality MVCT for contouring hip prostheses patients.