Image-guided moderately hypofractionated radiotherapy for localized prostate cancer: a multicentric retrospective study (IPOPROMISE).

BACKGROUND: Moderate hypofractionated radiotherapy is a treatment option for the cure of localized prostate cancer (PCa) patients based on the results of randomized prospective trials, but there is a clinical concern about the relatively short length of follow-up, and real-world results on outcome and toxicity based on cutting-edge techniques are lacking. The objective of this study is to present the long-term results of a large multicentric series. MATERIALS AND METHODS: We retrospectively evaluated 1325 PCa patients treated with daily volumetric image-guided hypofractionated radiotherapy between 2007 and 2020 in 16 Centers. For survival endpoints, we used Kaplan-Meier survival curves and fitted univariate and multivariable Cox's proportional hazards regression models to study the association between the clinical variables and each survival type. RESULTS: At the end of the follow-up, 11 patients died from PCa. The 15-year values of cancer-specific survival (CSS) and biochemical relapse-free survival (b-RFS) were 98.5% (95%CI 97.3-99.6%) and 85.5% (95%CI 81.9-89.4%), respectively. The multivariate analysis showed that baseline PSA, Gleason score, and the use of androgen deprivation therapy were significant variables for all the outcomes. Acute gastrointestinal (GI) and genitourinary (GU) toxicities of grade ≥ 2 were 7.0% and 16.98%, respectively. The 15-year late grade ≥ 2 GI and GU toxicities were 5% (95%CI 4-6%) and 6% (95%CI 4-8%), respectively. CONCLUSION: Real-world long-term results of this multicentric study on cutting-edge techniques for the cure of localized PCa demonstrated an excellent biochemical-free survival rate of 85.5% at 15 years, and very low rates of ≥ G3 late GU and GI toxicity (1.6% and 0.9% respectively), strengthening the results of the available published trials.

Prostate Imaging for Local Recurrence Reporting and Data System for Biparametric Magnetic Resonance Imaging: A Proposal.

We investigated a novel dedicated Prostate Imaging for Local Recurrence Reporting and Data System (PI-RRADS) in biochemical recurrence after radiotherapy (RT) and rad- ical prostatectomy (RP) evaluating biparametric magnetic resonance imaging (bpMRI) exams, at 3T MRI of 55 patients. Associating bpMRI and biochemical recurrence data, we calculated bpMRI diagnostic accuracy. Four probability categories, from 1 (very low) to 4 (very high), were distinguished. In 20 patients with radiotherapy, 25% and 75% of lesions were reported as PI-RRADS 3, and 4, respectively. In 35 patients with radi- cal prostatectomy, 7.7% of lesions were included in PI-RRADS 1-2, whereas 40.4% and 51.9% in PI-RRADS 3 and 4 categories, respectively. Excellent agreement and significant correlation between bpMRI and biochemical recurrence were found. BpMRI showed sensitivity, specificity, positive predictive value, negative predictive value, false-posi- tive value, false-negative value, and total diagnostic accuracy of 96.15%, 86.7%, 97.4 %, 81.25%, 13.3%, 3.8% and 94.6%, respectively. BpMRI-based PI-RRADS allows the detection and localization local recurrence in biochemical recurrence after RT and RP contributing in clinical management and treatment.

A predictive model of polymetastatic disease from a multicenter large retrospectIve database on colorectal lung metastases treated with stereotactic ablative radiotherapy: The RED LaIT-SABR study.

Aim: Stereotactic ablative radiotherapy (SABR) showed increasing survival in oligometastatic patients. Few studies actually depicted oligometastatic disease (OMD) evolution and which patient will remain disease-free and which will rapidly develop a polymetastatic disease (PMD) after SABR. Therefore, apart from the number of active metastases, there are no clues on which proven factor should be considered for prescribing local treatment in OMD. The study aims to identify predictive factors of polymetastatic evolution in lung oligometastatic colorectal cancer patients. Methods: This international Ethical Committee approved trial (Prot. Negrar 2019-ZT) involved 23 Centers and 450 lung oligometastatic patients. Primary end-point was time to the polymetastatic conversion (tPMC). Additionally, oligometastases number and cumulative gross tumor volume (cumGTV) were used as combined predictive factors of tPMC. Oligometastases number was stratified as 1, 2-3, and 4-5; cumGTV was dichotomized to the value of 10 cc. Results: The median tPMC in the overall population was 26 months. Population was classified in the following tPMC risk classes: low-risk (1-3 oligometastases and cumGTV ≤ 10 cc) with median tPMC of 35.1 months; intermediate-risk (1-3 oligometastases and cumGTV > 10 cc), with median tPMC of 13.9 months, and high-risk (4-5 oligometastases, any cumGTV) with median tPMC of 9.4 months (p = 0.000). Conclusion: The present study identified predictive factors of polymetastatic evolution after SABR in lung oligometastatic colorectal cancer. The results demonstrated that the sole metastases number is not sufficient to define the OMD since patients defined oligometastatic from a numerical point of view might rapidly progress to PMD when the cumulative tumor volume is high. A tailored approach in SABR prescription should be pursued considering the expected disease evolution after SABR, with the aim to avoid unnecessary treatment and toxicity in those at high risk of polymetastatic spread, and maximize local treatment in those with a favorable disease evolution.

S-PI-RADS and PI-RRADS for Biparametric MRI in the Detection of Prostate Cancer and Post-treatment Local Recurrence.

The application of biparametric magnetic resonance imaging (bpMRI) [T2-weighted (T2W) and diffusion weighted imaging (DWI)/apparent diffusion coefficient (ADC)] using dedicated structured methods, such as Simplified Prostate Imaging Reporting and Data System (S-PI-RADS) for the detection, categorization, and management of prostate cancer (PCa) is reported. Also, Prostate Imaging Reporting for Local Recurrence and Data System (PI-RRADS) for the detection and assessment of the probability of local recurrence after radiotherapy (RT) or radical prostatectomy (RP) in patients with biochemical recurrence (BCR) is proposed. Both S-PI-RADS and PI-RRADS assign to DWI/ADC a main role for the above purpose. S-PI-RADS identifies four categories and, on the basis of the qualitative and quantitative analysis of the restricted diffusion on ADC map and lesion volume, distinguishes two categories of lesions: category 3 (moderately homogeneous hypointense on ADC map) and category 4 (markedly homogeneous or inhomogeneous hypointense on ADC map). Ιn category 3, two subcategories (3a: volume <0.5 cm3 and 3b: volume ≥0.5 cm3) suggesting clinical management. PI-RRADS distinguishes four assessment categories and suggests the stratification of the probability (ranging from very low for category 1 to very high for category 4) of local disease recurrence. In clinical practice, S-PI-RADS and PI-RRADS, based on bpMRI represent a potential valid approach that may facilitates the detection and management of PCa and for detecting local recurrence after treatment improving communication with other professionals.

Reliability of algebraic sum to evaluate adjuvant pelvic radiotherapy and vaginal cuff brachytherapy cumulative doses in uterine cancers.

Purpose: To evaluate the reliability of algebraic sum with respect to rigid fusion of treatment plans related to adjuvant external beam pelvic radiotherapy (APR) and vaginal cuff high-dose-rate brachytherapy (BT) in uterine cancer patients. Material and methods: For algebraic sum, APR and BT doses were mathematically added. Rigid fusion was realized overlapping computed tomography (CT) images of APR and BT treatment plans. Rectum and bladder were considered reference organs at risk (OARs). Following dose (D) parameters were examined: Dmax (0.5 cc), D20% and D50% for rectum, Dmax (0.5 cc) and D50% for bladder; for each parameter, differences between the two adopted methods were reported as Δ-values. Results: Twenty uterine cancer patients submitted to radical surgery followed by APR plus vaginal cuff BT were reviewed. APR was done with a dose of 25 × 2 Gy. All patients also receveid a vaginal cuff boost with BT at the dose of 2 × 5 Gy. Differences between mean cumulative doses calculated with rigid fusion and algebraic sum were evaluated. For the rectum and bladder ΔD50%, there were no significant differences, and BT contribution resulted minimal. An apparent significant difference value was registered in bladder ΔDmax (0.5 cc). No toxicity was observed. Conclusions: In uterine cancer patients submitted to APR and vaginal cuff BT, algebraic sum and rigid plan fusion of doses allowed to obtain similar results in evaluating cumulative OARs' doses. Further investigations and increased number of patients are recommended to confirm our findings.

Outcomes and toxicities of re-irradiation for prostate cancer: A systematic review on behalf of the Re-Irradiation Working Group of the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

AIMS: The best therapeutic approach for local relapses of previously irradiated prostate cancer (PC) is still not defined. Re-irradiation (Re-I) could offer a chance of cure for highly selected patients, although high quality evidences are lacking. The aim of our study is to provide a literature review on efficacy and safety of Re-I. METHODS: Only studies where Re-I field overlaps with previous radiotherapy were considered. To determine 2 and 4 years overall mortality (OM), 2 and 4 years biochemical failure (BF) and pooled acute and late G ≥ 3 toxicities rate, a meta-analysis over single arm study was performed. RESULTS: Thirty-eight studies with 1194 patients were included. Median follow-up from Re-I was 30 months (10-94 months). Brachytherapy (BRT) was the most used Re-I technique (27 studies), followed by Stereotactic Body Radiotherapy (SBRT) (9) and External Beam Radiation Therapy (EBRT) (2). Re-I prescription doses ranged from 19 Gy in single HDR fraction to 145 Gy (interstitial BRT). The pooled 2 and 4 years OM rates were 2.1% (95%CI:1.1-3.7%, P < 0.001) and 12.5% (95%CI:8.1-19.5%; P < 0.001). The pooled 2 years BF rate was 24% (95% CI: 19.1-30.2%, P < 0.001). The pooled 4 years BF was 35.6% (95% CI: 28.7-44.3%, P < 0.001). The pooled result of G ≥ 3 acute toxicity was 1.4% (95%CI: 0.7-3%, P < 0.001). One hundred and three G ≥ 3 late adverse events were reported, with a pooled result of G ≥ 3 late toxicity of 8.7% (95%CI: 5.8-13%, P < 0.001). CONCLUSIONS: Re-I of local failures from PC showed promising OM and biochemical control rates with a safe toxicity profile.

Long-term palliation of lymph node oligometastatic ovarian carcinoma after repeated stereotactic body radiotherapy: case report.

INTRODUCTION: Oligometastatic disease has emerged as an intermediate state between localized and systemic cancer. Improvements in diagnostic modalities such as functional imaging allow a greater frequency of oligometastases diagnosis. Patients with selected oligometastatic epithelial ovarian carcinoma (EOC) may be treated with metastasis-directed stereotactic body radiotherapy (SBRT) rather than chemotherapy. CASE DESCRIPTION: We describe a 58-year-old woman who underwent surgery and chemotherapy for an EOC. The patient underwent 3 chemotherapy lines for recurrence of disease, but had allergic reactions and serious hematologic toxicity. During follow-up, lymph node oligometastases were diagnosed and treated with repeated SBRT because the patient refused further chemotherapy. No side effects were observed after each course of SBRT and the patient obtained complete response of all irradiated sites. CONCLUSIONS: SBRT is a promising treatment approach for recurrent oligometastatic EOC with a high control rate and irrelevant iatrogenic toxicity. The possibility to repeat SBRT courses when new oligometastases are encountered in other sites resulted in an adequate long-term palliation approach.

Twelve-year results of LINAC-based radiosurgery for vestibular schwannomas.

PURPOSE: To report long-term outcomes of 53 patients with vestibular schwannomas (VS) submitted to a single high-dose LINAC-based radiosurgery (SRS) in our institution. METHODS: 48 (92%) patients were evaluable for clinical and MRI response as well as late toxicity. At a median follow-up of 12 years (range 2-16 years), local control (LC), hearing capacity, trigeminal and facial nerve function, and toxicity were assessed. Hearing capacity was classified according to the Gardner-Robertson scale, where class I-II patients had "serviceable hearing." RESULTS: Median dose of SRS was 16.5 Gy (range 13-20 Gy) and median tumor volume 1.7 cm3 (range 0.09-7.4 cm3). 35 (73%) patients were treated with SRS alone, in the remaining 13 (27%) patients, SRS was performed as salvage therapy for recurrent or progressive tumors after previous microsurgery. Before SRS, 44 patients (92%) had hearing loss and 25 (52%) had "non-serviceable" hearing. Tumor extension, classified with Koos categories, was grade I-II in 27 (56%) and grade III-IV in 21 (44%) cases. LC was 100% and hearing preservation in "serviceable hearing" patients was 91%. 4 (11%) patients developed incomplete and intermittent ipsilateral facial nerve palsy which regressed in a median time of 6 months. Trigeminal toxicity was registered in 11 (23%) patients, reversible in 6 (13%) and permanent in 5 (10%). Only Koos tumor grade III-IV significantly influenced late toxicity (p = 0.01). CONCLUSION: LC and hearing preservation after SRS were excellent. Toxicity proved acceptable. Although the median administered dose (16.5 Gy) was rather high, the only factor which significantly influenced late toxicity was Koos tumor grade III-IV.

Accelerated partial-breast irradiation with high-dose-rate brachytherapy: Mature results of a Phase II trial.

PURPOSE: The purpose of this study was to report mature clinical and cosmetic results of accelerated partial-breast irradiation with interstitial multicatheter high-dose-rate brachytherapy (HDR-BRT) in patients with early breast cancer. METHODS AND MATERIALS: 133 patients were recruited in a Phase II trial of exclusive HDR-BRT. Inclusion criteria were age ≥40 years, PS 0-2, unifocal invasive ductal cancer, intraductal cancer component <25%, negative axillary nodes, and tumor size ≤2.5 cm. Treatment schedule was 4 Gy twice a day up to a total dose of 32 Gy in eight fractions. RESULTS: Median age was 67 years (range, 42-85). There were 7 (5%) pT1a, 48 (36%) pT1b, 72 (54%) pT1c, and 6 (5%) pT2. Estrogen and progesterone receptors were positive in 119 (89%) and 93 (70%) patients, respectively. The median followup was 110 months (range, 12-163). After HDR-BRT, there were 3 (2%) in-field breast recurrences and 1 (1%) out-field breast recurrence. 5 (4%) patients developed contralateral breast cancer, another one (1%) isolated regional relapse in axillary node and 3 (2%) distant progression of disease. 19 (14%) patients reported a second primary cancer. 5-, 10-, and 13-year overall survival and cancer-specific survival were 95% and 100%, 84.5% and 100%, and 81.4% and 100%, respectively. Cosmetic outcome was excellent in 80% of cases. Late toxicity was significantly related to the skin administered doses (≤55% vs. > 55% of the prescribed dose, p < 0.05). CONCLUSIONS: Accelerated partial-breast irradiation delivered with HDR-BRT in selected patients with breast cancer was associated to high local control and survival with excellent cosmetic outcomes overall when skin dose was ≤55%.

A prospective phase II trial on reirradiation of brain metastases with radiosurgery.

PURPOSE: In our previous published trial on radiosurgery (SRS) of recurrent brain metastases (BM) after whole brain radiotherapy (WBRT), Karnofsky performance status (KPS) and administered dose conditioned outcome and late toxicity, respectively. Brain radionecrosis was registered in 6% of patients. With the aim to obtain similar satisfactory outcomes and limit toxicity, we started a phase II trial in which reirradiation of BM with SRS were done using a tighter patient selection. MATERIALS AND METHODS: Patients with BM recurring after WBRT were recruited for reirradiation with SRS. Only patients with good KPS (≥70), good neurologic functional score (NFS 0-1) and lesions with a diameter ≤20 mm were considered eligible for retreatment. Dose exceeding 20 Gy was never administered. RESULTS: The 59 patients reirradiated had 109 BM with a diameter range of 6-20 mm. Median interval between prior WBRT and SRS was 15 months and median SRS administered dose was 18 Gy (range 10-20 Gy). Complete and partial response (CR, PR) was obtained in 42% of patients with 2 years of control rate of 81%. Median overall survival (OS) after reirradiation was 14 months. No radionecrosis was detected. CONCLUSIONS: Analysis of our current trial compared with results of our previous data suggests that a tighter patient selection (KPS ≥ 70; NFS 0-1, BM with ≤20 mm of diameter) and SRS dose ≤20 Gy allowed a high OS rate, a good percentage of CR and PR which last for >2 years, and no brain radionecrosis.

Combined surgery and radiotherapy as curative treatment for tracheal adenoid cystic carcinoma: a case report.

BACKGROUND: Adenoid cystic carcinoma of the trachea is a rare tumor, characterized by slow growth and low rate of local and distant metastasis. When achievable, complete surgical resection represents the optimal treatment approach, with the highest results in terms of overall survival. Radiation therapy is a reasonable alternative in cases of inoperable disease. CASE PRESENTATION: We report a case of an 82-year-old white man affected by primary adenoid cystic carcinoma of the trachea, treated with debulking surgery and radiotherapy on the residual disease. A three-dimensional conformal radiation therapy was conducted. The total dose amounted to 70 Gy, administered in 35 fractions of 2 Gy. The medium doses given to the esophagus and lungs were 23 Gy and 4.2 Gy respectively. The maximum dose delivered to the spinal cord was 31 Gy with satisfactory results in terms of local control of the disease. CONCLUSION: A combined approach of surgical resection followed by radiotherapy on the residual disease provided an excellent result in terms of disease control, quality of life, and overall survival in a patient with locally advanced tracheal adenoid cystic carcinoma.

Image-guided-radiotherapy retreatment of spine metastasis: a case report and radiobiological evaluation.

AIMS AND BACKGROUND: The present case report describes vertebral metastasis retreatment using kilovoltage cone-beam computed tomography (CBCT) for setup error correction, in order to improve target irradiation and prevent spinal cord toxicity. We evaluated the feasibility of the second radiation therapy course on the overlapping treatment volume. METHODS AND STUDY DESIGN: A patient with metastatic kidney cancer, previously treated to the tenth dorsal vertebra with conventional radiation planning (21 Gy; 3 x 7 Gy), underwent retreatment. In order to deliver 30 Gy (15 x 2 Gy) to the target volume with the second irradiation, we evaluated the residual dose that could be received by the spinal cord. We calculated the biologically effective dose according to the linear-quadratic model, using an alpha/beta ratio of 2 Gy. A 3-dimensional conformal plan was generated; CBCT imaging was used to ensure accurate repositioning. RESULTS: A total of 15 CBCT scans were performed; the mean setup corrections in the lateral, longitudinal and vertical directions were 3.38 mm (SD 2.09; range, -0.2 mm division by 7.6 mm), 2.13 mm (SD 3.38; range, -5.9 mm divison by 6 mm), and -1.28 mm (SD 2.02; range, -7.1 mm division by 0.3 mm), respectively. CONCLUSION: Image-guided radiotherapy is an alternative approach for the retreatment of spine tumors; it ensures accurate patient setup correction and high-precision treatment delivery, which are required for target volumes very close to critical structures.

Retro-orbital granulocytic sarcoma: case report.

Granulocytic sarcomas (chloromas) are rare extra-medullary tumors arising from primitive granulocytic cells. The term "chloroma" is derived from the Greek word chloros (green), and it refers to the frequently greenish color of the tumor, which is due to the presence and oxidation of the myeloperoxidase enzyme. These tumors can arise de novo or can be associated with other myeloid disorders, such as acute or chronic myeloid leukemia, myeloproliferative or myelodysplastic conditions. Presentation can occur prior to, in association with the underlying myeloid disorder, or upon relapse. The location of the tumor can vary: sub-periosteal bone, skull, pelvis, ribs, sternum or lymph nodes. We report the case of a 58-year-old man who presented right exophthalmos and ophthalmoplegy with computerized tomography (CT) evidence of a retro-orbital mass, which histology confirmed to be a granulocytic sarcoma.