Tomotherapy-based moderate hypofractionation for localized prostate cancer: a mono-institutional analysis.

Background: To date, few studies have been published on image-guided helical tomotherapy (HT) in a moderate hypofractionation of localized PCa. We report outcome and toxicity of localized PCa patients treated with HT-based moderate hypofractionated radiotherapy. Materials and methods: 76 patients were retrospectively analyzed. A total dose of 60 Gy (20 × 3 Gy) or 67.5 Gy (25 × 2.7 Gy) was prescribed. The χ2 test was used to analyze associations between toxicity and dosimetric and clinical parameters. The Cox proportional hazard regression model was used for multivariate analysis. Kaplan-Meier method was used for survival analysis. Results: median follow-up was 42.26 months [interquartile (IQR), 23-76). At 4-year, overall survival (OS) and metastasis-free survival (MFS) were 91% and 89%, respectively. At multivariate analysis, smoking habitude was associated with MFS [hazard ratio (HR) 7.32, 95% CI: 1.57-34.16, p = 0.011]. Acute and late grade ≥ 2 gastro-intestinal (GI) toxicity was observed in 6.5% and 2.6% of patients, respectively. Acute and late grade ≥ 2 genito-urinary (GU) toxicity were 31.5% and 3.9%. Four-year late GI and GU grade ≥ 2 toxicity were 3% and 7%, respectively. Acute GI toxicity was associated with statins medication (p = 0.04) and androgen deprivation therapy (p = 0.013). Acute GU toxicity was associated with the use of anticoagulants (p = 0.029) and antiaggregants (p = 0.013). Conclusions: HT-based moderate hypofractionation shows very low rates of toxicity. Smoking habitude is associated with the risk of developing metastases after radical treatment for localized PCa.

FDG-PET/CT in the Radiotherapy Treatment Planning of Locally Advanced Anal Cancer: A Monoinstitutional Experience.

AIMS: Radiotherapy with concurrent 5-fluorouracil/mitomycin-C based chemotherapy has been established as definitive standard therapy approach for anal cancer. Intensity Modulated Radiotherapy (IMRT) leads to a precise treatment of the tumor, allowing dose escalation on Gross Tumor Volume (GTV), with a surrounding healthy tissues sparing. Our study assessed the impact of 18-Fluorodeoxyglucose positron emission tomography (18FDG-PET/CT) on the radiotherapy contouring process and its contribution to lymphatic spread detection, resulting to a personalization of Clinical Target Volume (CTV) and dose prescription. METHODS: Thirty-seven patients, with histologically proven squamous cell carcinoma of the anal canal (SCCAC) were analyzed. All patients were evaluated with history and physical examination, trans-anal endoscopic ultrasound, pelvis magnetic resonance imaging (MRI), computed tomography (CT) scans of the chest, abdomen and pelvis and planning 18FDG-PET/CT. The GTV and CTV were drawn on CT, MRI and 18FDG-PET/CT fused images. RESULTS: Thirty-four (91%) out of 37 patients presented lymph nodes involvement, in one or more areas, detected on 18FDG-PET/CT and/or MRI. The 18FDG-PET/CT showed positive lymph nodes not detected on MRI imaging (PET+, MRI-) in 14/37 patients (38%). In 14 cases, 18FDG-PET/CT allowed to a dose escalation in the involved nodes. The 18FDG-PET/CT fused images led to change the stage in 5/37(14%) cases: four cases from N0 to N1 (inguinal lymph nodes) and in one case from M0 to M1 (common iliac lymph nodes). CONCLUSIONS: The 18FDG-PET/CT has a potentially relevant impact in staging and target volume delineation/definition in patients affected by anal cancer. In our experience, clinical stage variation occurred in 14% of cases. More investigations are needed to define the role of 18FDG-PET/CT in the target volume delineation of anal cancer.

Helical tomotherapy re-irradiation for patients affected by local radiorecurrent prostate cancer.

BACKGROUND: Salvage re-irradiation in patients affected by radiorecurrent prostate cancer might be a valid as well as challenging treatment option. The aim of this study was to evaluate feasibility and toxicity of salvage external beam radiotherapy (EBRT) re-treatment in patients affected by radiorecurrent prostate cancer within the prostate gland or the prostate bed. MATERIALS AND METHODS: 15 patients underwent EBRT re-treatment using helical tomotherapy (HT), with daily Megavolt computed tomography image-guidance. We registered toxicity according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Biochemical relapse was defined as a PSA increase > 20% compared with the pre-EBRT re-treatment value. Survival curves were calculated using the Kaplan-Meier method. RESULTS: All patients received a total dose of 50 Gy (25 × 2 Gy), and 7 (46.6%) had concomitant androgen deprivation therapy (median duration of 12 months). With a median follow-up of 40.9 months, the 2-year and 4-year biochemical relapse-free survival were 55% and 35%, respectively. Acute and late genito-urinary (GU) toxicity ≥2 were recorded in 4 (26.6%) and 5 (33.3%) patients, respectively, and the 4-year late GU toxicity was 30%. Acute gastrointestinal toxicity ≥2 was recorded in 2 (13.3%) cases, whereas no patient experienced late toxicity. CONCLUSIONS: Despite the inherent bias of a retrospective analysis, our long-term results showed a low toxicity profile with a relatively low rate of biochemical control for HT re-treatment in patients affected by local radiorecurrent prostate cancer. Prospective trials are needed to investigate the role of EBRT in this setting.

Hypofractionated whole breast radiotherapy with or without hypofractionated boost in early stage breast cancer patients: a mono-institutional analysis of skin and subcutaneous toxicity.

BACKGROUND: Our study evaluated skin and subcutaneous toxicity analyzing its correlation with patient- and treatment-related factors in a large mono-institutional series of women with early stage breast cancer treated with adjuvant hypofractionated whole breast radiotherapy (WBRT) with or without a sequential hypofractionated boost (HB). METHODS: Two hundred and nineteen patients, median age 62 years, received adjuvant hypofractionated WBRT in 16 fractions to a total dose of 42.4 Gy. Patients with negative prognostic factors received a HB of 2.65 Gy for 4 or 5 (patients with focal positive surgical margins) fractions. Systemic adjuvant treatments were hormonal therapy (HT) and/or chemotherapy (CHT) and/or Trastuzumab. Toxicities were assessed using the Common Terminology Criteria for Adverse Events (CTCAE 4.03) scale at 5th, 10th, 16th, 20th day from the start of radiotherapy (RT) and 1, 6 and 12 months after the end of RT. Univariate and multivariate analysis estimated toxicity predictive factors. RESULTS: No case of treatment interruption and no acute or late G3 toxicities occurred. In the univariate analysis HB administration resulted a risk factor for acute toxicity, while CHT administration and number of excised lymph nodes ≥ 10 resulted a risk factor for late toxicity. In the multivariate analysis none of the evaluated factors emerged a risk factor for acute and/or late toxicity. CONCLUSIONS: Our results confirmed that hypofractionated WBRT even followed by a HB resulted safe and well tolerated. Longer follow-up is warranted to estimate late toxicity and treatment outcomes.

Partial breast irradiation with interstitial multi-catheter high-dose-rate brachytherapy. Long-term results of a phase II prospective study.

PURPOSE: We report the long-term results of phase II prospective study with accelerated partial breast irradiation (APBI) using interstitial multi-catheter high-dose-rate brachytherapy. METHODS: 240 patients received APBI (4Gy, twice daily; total dose 32Gy). RESULTS: Median follow-up was 96months. Recurrences in the treated breast developed in 8 patients (3.3%) at a median of 73months after APBI. The 5- and 10-year cumulative incidences were respectively, 1.8% (95%CI: 0.6-4.3) and 6.6% (95%CI: 2.7-12.9). Regional recurrences developed in 5 patients (2%) at a median of 28months and distant metastases in 8 (3.3%) at a median of 32.5months. Breast cancer specific mortality occurred in 6 patients (2.5%) at a median of 60months. Acute toxicity developed in 71 (29.6%) patients (G1 in 60 and G2 in 11). Almost all were skin toxicity and hematomas. Late toxicity was observed in 90 patients (37.5%), G1 in 97 cases and G2 in 11. Some patients presented with more than one type of toxicity. Teleangectasia and fibrosis were the most common (48 and 44 cases respectively), followed by fat necrosis (in 18 patients) Tamoxifen emerged as the only risk factor for breast fibrosis (p=0.007). Cosmetic results were judged by the physicians as excellent in 174 (83.7%) patients, good in 25 (12%) fair in 8 (3.8%) and poor in 1 (0.5%); 174 patients (83.7%) judged outcomes as excellent, 26 (12.4%) as good, 7 (3.4%) as fair and 1 (0.5%) as poor. Physician/patient agreement was good (weighted k-value 0.72). CONCLUSIONS: APBI with interstitial multi-catheter brachytherapy was associated with good outcomes, low relapse and toxicity rates. Few events during this long-term follow-up preclude identifying specific features of patients at risk of relapse and illustrate the need for a large data-base.

Statins Protect Against Acute RT-related Rectal Toxicity in Patients with Prostate Cancer: An Observational Prospective Study.

AIM: To analyze risk factors for acute rectal toxicity during hypofractionated intensity-modulated radiotherapy (IMRT) for prostate cancer. PATIENTS AND METHODS: A total of 195 patients received 74.25 Gy in 33 fractions to the prostate and, if involved, to the seminal vescicles (SV). When the risk of SV involvement was >15% according to the Roach's formula, they received 62 Gy in 33 fractions. Overall, 107/195 patients (54.87%) received hormonal therapy (luteinizing hormone-releasing hormone analogue, anti-androgen, or both). Common Terminology Criteria for Adverse Events version 3.0 was used to classify rectal toxicity. RESULTS: Acute rectal toxicity occurred in 79 (40.51%) patients (grade 1 in 44). In univariate analysis, use of calcium channel blockers significantly reduced the acute rectal toxicity rate and 3-hydroxy-methylglutaryl CoA reductase inhibitors (statins) significantly reduced the rectal toxicity rate and grade. In multivariate analysis, only statin use was an independent protective factor. CONCLUSION: In patients with prostate cancer treated with a moderate hypofractionated IMRT schedule, use of statins lowered the incidence and grade of acute rectal toxicity.

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.

Encrusted cystitis after definitive radiotherapy for cervical cancer: a case report.

PURPOSE: Encrusted cystitis is a rare chronic inflammatory disease characterized by calcified plaques of the bladder, previously altered by varies conditions as urological procedures, caused by urea-splitting bacteria. Only one case has been reported on encrusted cystitis occurring after surgery and radiation therapy for a pelvic neoplasm. We report on encrusted cystitis occurred after definitive radiotherapy for bulky uterine cervix cancer, and examine the doses to the bladder wall and the procedure of radiation treatment performed as a possible cause of the onset of the disease. CASE PRESENTATION: A 52-year-old female developed encrusted cystitis, caused by Corynebacterium spp., after 14 months from definitive chemo-radiotherapy and 2/D brachytherapy treatment for FIGO stage IB2 uterine cervix cancer. For pelvic radiotherapy, the mean bladder dose was 48.47 Gy (range 31.20-51.91); maximal bladder point doses at each brachytherapy insertions were 7.62 Gy, 4.94 Gy and 6.27 Gy at first, second, and third fraction, respectively. Total biological effective dose (BED) at bladder point was 140.05 Gy3. The patient was administered antibiotic therapy with linezolid and urine acidification with vitamin C; dietary norms were also suggested. After therapy, complete remission of symptoms and radiological findings were achieved, and the planned surgery for removing the calcified plaques was not completed. After 5 years from the cervical cancer diagnosis, the patient was disease-free without urinary symptoms. CONCLUSIONS: The high doses administered to the bladder wall and the repeated catheterizations performed at each brachytherapy insertions may have favored the infection and promoted the occurrence of the encrusted cystitis.