Predictive value of Prostate Specific Antigen variations in the last week of salvage radiotherapy for biochemical recurrence of prostate cancer after surgery: A practical approach.

BACKGROUND: About a third of patients who underwent radical prostatectomy for prostate cancer (Pca) develop a biochemical failure (BF) within 10 years from surgery, and about a half of them receive salvage radiation therapy (SRT). Factors to predict risk to relapse after SRT are still lacking. Dynamic models, based on the assessment of changes in Prostate Specific Antigen (PSA) postsurgery seem to show good reliability. AIMS: The goal of the study was to identify a simple analytical method for the postsalvage radiation therapy biochemical failure (post-SRTBF) prediction before the end of the SRT, regardless of the PSA value at the beginning of the treatment (PSA start), measuring the PSA values at the start and 1 week before the end of SRT. METHODS: In a series of 83 patients treated with SRT for BF of Pca we measured PSA values at the first day and 1 week before the end of SRT. These values were used to define an analytical method for the post-SRTBF prediction. RESULTS: PSA value in patients without post-SRTBF show a significant difference in term of difference during the SRT with respect to patients with post-SRTBF. Starting from this difference, we identified a simple and practical analytical method for the post-SRTBF prediction before the end of the SRT. The data corresponds with the model and the analytical method is highly predictive (Sensitivity = 81%, Specificity = 85%, Accuracy = 83%). CONCLUSION: This study offers a new tool to early predict Pca relapse overtime and to select patients who can benefit from an early additional systemic treatment.

Re-irradiation With Carbon Ion Radiotherapy for Pelvic Rectal Cancer Recurrences in Patients Previously Irradiated to the Pelvis.

BACKGROUND/AIM: Re-irradiation of locally recurrent rectal cancer poses challenges due to the proximity of critical organs, such as the bowel. This study aimed at evaluating the safety and efficacy of re-irradiation with Carbon Ion Radiotherapy (CIRT) in rectal cancer patients with local recurrence. PATIENTS AND METHODS: Between 2014 and 2018, 14 patients were treated at the National Center of Oncological Hadrontherapy (CNAO Foundation) with CIRT for locally recurrent rectal cancer. RESULTS: All patients concluded the treatment. No G≥3 acute/late reaction nor pelvic infections were observed. The 1-year and 2-year local control rates were, 78% and 52%, respectively, and relapse occurred close to the bowel in 6 patients. The 1-year and 2-year overall survival rates were 100% and 76.2% each; while the 1-year and 2-year metastasis free survival rates were 64.3% and 43%. CONCLUSION: CIRT as re-irradiation for locally recurrent rectal cancer emerges as a safe and valid treatment with an acceptable rate of morbidity of surrounding healthy tissue.

Proton and carbon ion radiotherapy in skull base chordomas: a prospective study based on a dual particle and a patient-customized treatment strategy.

BACKGROUND: The aim of this study is to evaluate results in terms of local control (LC), overall survival (OS), and toxicity profile and to better identify factors influencing clinical outcome of skull base chordoma treated with proton therapy (PT) and carbon ion radiotherapy (CIRT). METHODS: We prospectively collected and analyzed data of 135 patients treated between November 2011 and December 2018. Total prescription dose in the PT group (70 patients) and CIRT group (65 patients) was 74 Gy relative biological effectiveness (RBE) delivered in 37 fractions and 70.4 Gy(RBE) delivered in 16 fractions, respectively (CIRT in unfavorable patients). LC and OS were evaluated using the Kaplan-Meier method. Univariate and multivariate analyses were performed, to identify prognostic factors on clinical outcomes. RESULTS: After a median follow-up of 44 (range, 6-87) months, 14 (21%) and 8 (11%) local failures were observed in CIRT and PT group, respectively. Five-year LC rate was 71% in CIRT cohort and 84% in PT cohort. The estimated 5-year OS rate in the CIRT and PT group was 82% and 83%, respectively. On multivariate analysis, gross tumor volume (GTV), optic pathways, and/or brainstem compression and dose coverage are independent prognostic factors of local failure risk. High rate toxicity grade ≥3 was reported in 11% of patients. CONCLUSIONS: Particle radiotherapy is an effective treatment for skull base chordoma with acceptable late toxicity. GTV, optic pathways, and/or brainstem compression and target coverage were independent prognostic factors for LC. KEY POINTS: • Proton and carbon ion therapy are effective and safe in skull base chordoma.• Prognostic factors are GTV, organs at risk compression, and dose coverage.• Dual particle therapy and customized strategy was adopted.

Rectum Dose Constraints for Carbon Ion Therapy: Relative Biological Effectiveness Model Dependence in Relation to Clinical Outcomes.

The clinical application of different relative biological effectiveness (RBE) models for carbon ion RBE-weighted dose calculation hinders a global consensus in defining normal tissue constraints. This work aims to update the local effect model (LEM)-based constraints for the rectum using microdosimetric kinetic model (mMKM)-defined values, relying on RBE translation and the analysis of long-term clinical outcomes. LEM-optimized plans of treated patients, having suffered from prostate adenocarcinoma (n = 22) and sacral chordoma (n = 41), were recalculated with the mMKM using an in-house developed tool. The relation between rectum dose-volume points in the two RBE systems (DLEM|v and DMKM|v) was fitted to translate new LEM-based constraints. Normal tissue complication probability (NTCP) values, predicting late rectal toxicity, were obtained by applying published parameters. No late rectal toxicity events were reported within the patient cohort. The rectal toxicity outcome was confirmed using dosimetric analysis: DMKMVHs lay largely below original constraints; the translated DLEM|v values were 4.5%, 8.3%, 18.5%, and 35.4% higher than the nominal DMKM|v of the rectum volume, v-1%, 5%, 10% and 20%. The average NTCP value ranged from 5% for the prostate adenocarcinoma, to 0% for the sacral chordoma group. The redefined constraints, to be confirmed prospectively with clinical data, are DLEM|5cc ≤ 61 Gy(RBE) and DLEM|1cc ≤ 66 Gy(RBE).

Feasibility of Carbon Ion Radiotherapy in the Treatment of Gynecological Melanoma.

BACKGROUND: Malignant melanoma of the lower genital tract is a rare disease known to have a poor prognosis. Because of the high rate of distant metastasis and unsatisfactory survival benefit, a more conservative treatment approach, instead of extensive surgery, may be warranted. Gynecological melanoma is a radioresistant tumor, an ideal disease to test the biological efficacy of carbon ion radiotherapy (CIRT). AIM: To report our preliminary experience with CIRT in the treatment of gynecological melanoma at the National Center of Oncological Hadrontherapy (CNAO). PATIENTS AND METHODS: Between January 2016 and February 2017, four patients were admitted for CIRT at CNAO. A case of cervical melanoma was treated with palliative aim because of large volume macroscopic disease, while three cases of vaginal melanoma were irradiated with a total dose of 68.8 Gy (relative biological effectiveness) in 16 fractions delivered over 4 weeks (4 days a week). RESULTS: The age of women ranged between 49 and 72 (median=60.5 years) years. Treatment was well tolerated in all patients and all women completed the scheduled treatment course. During CIRT, toxicity was mild. For patients with vaginal disease, local control was 10.23 and 12.6 months, while that for cervical malignant melanoma was 7.3 months. All patients experienced systemic progression, with median distant metastasis-free survival of 11.7 months. The median overall survival for the whole patient group was 11.41 months. CONCLUSION: In our first experiences, CIRT appears to be a safe non-invasive option for malignant melanoma of the lower genital tract, but more data and longer follow-up are necessary in order to evaluate the effectiveness and late effects.

Carbon Ion Radiotherapy in the Management of Unusual Liposarcomas: A Case Report.

BACKGROUND: Liposarcomas are the most common soft-tissue sarcomas in adulthood. Orbital and spermatic cord liposarcomas are uncommon and there is no consensus on their management. The treatment of choice is wide excision, which may be destructive and lead to unacceptable morbidity. When surgery is declined by patients and in recurrent disease, management can be challenging. We report two cases of liposarcoma treated with carbon ion radiotherapy at the National Center for Oncological Hadrontherapy (Fondazione CNAO) in Italy. CASE REPORT: A woman with orbital liposarcoma and a man with spermatic cord liposarcoma were referred to our Center and accepted for carbon ion radiotherapy. The treatment was well tolerated and late toxicities were mild. Good local control was achieved in patients. CONCLUSION: In our experience, carbon ion radiotherapy is an effective and safe option, especially in cases of tumor at high risk for local relapse, in patients with multiple local recurrences, and in patients who refuse destructive surgery.

Carbon Ion Radiotherapy in the Management of the Tumors of the Peripheral Nervous System.

BACKGROUND/AIM: Malignant peripheral nerve sheaths tumors (MPNST) are rare, highly aggressive and radioresistant tumors of soft tissue. Carbon ion radiotherapy (CIRT) seems to be an attractive treatment option when surgery is not possible or refused by the patient. The aim of this study was to report our preliminary results (outcomes and toxicity) of CIRT in the treatment of MPNSTs. PATIENTS AND METHODS: Our study retrospectively analyzed 13 patients (median age=54 years; range=23-72 years) with MPNST treated with CIRT for a median total dose of 73.6 Gy (relative biological effectiveness) (range=70.4-76.8 Gy) between 2013 and 2016. RESULTS: Six local progressions were recorded, with a median local progression-free survival of 23.2 months (range=2.2-45.4 months). Acute toxicities were mild. Late toxicity of grade 2 or more was noted in two patients. CONCLUSION: CIRT yielded good local control with a low rate of acute and late toxicities.