Radiotherapy at oligoprogression for metastatic castration-resistant prostate cancer patients: a multi-institutional analysis.

PURPOSE: To retrospectively estimate the impact of radiotherapy as a progression-directed therapy (PDT) in oligoprogressive metastatic castration-resistant prostate cancer (mCRPC) patients under androgen receptor-target therapy (ARTT). MATERIALS AND METHODS: mCRPC patients are treated with PDT. End-points were time to next-line systemic treatment (NEST), radiological progression-free survival (r-PFS) and overall survival (OS). Toxicity was registered according to Common Terminology Criteria for Adverse Events v4.0. Survival analysis was performed using the Kaplan-Meier method; univariate and multivariate analyses were performed. RESULTS: Fifty-seven patients were analyzed. The median follow-up after PDT was 25.2 months (interquartile, 17.1-44.5). One-year NEST-free survival, r-PFS and OS were 49.8%, 50.4% and 82.1%, respectively. At multivariate analysis, polymetastatic condition at diagnosis of metastatic hormone-sensitive prostate cancer (mHSPC) (HR 2.82, p = 0.004) and PSA doubling time at diagnosis of mCRPC (HR 2.76, p = 0.006) were associated with NEST-free survival. The same variables were associated with r-PFS (HR 2.32, p = 0.021; HR 2.24, p = 0.021). One patient developed late grade ≥ 2 toxicity. CONCLUSION: Our study shows that radiotherapy in oligoprogressive mCRPC is safe, is effective and seems to prolong the efficacy of ARTT in patients who otherwise would have gone systemic treatment switch, positively affecting disease progression. Prospective trials are needed.

Stereotactic or conventional radiotherapy for macroscopic prostate bed recurrence: a propensity score analysis.

PURPOSE: To assess outcomes between salvage radiation therapy (SRT) with curative intent and stereotactic radiotherapy for macroscopic prostate recurrence (SSRT) after radical prostatectomy (RP). In order to compare these two different options, we compared their outcomes with a propensity score-based matched analysis. METHODS: Data from 185 patients in seven Italian centres treated for macroscopic prostate bed recurrence after RP were retrospectively collected. To make a comparison between the two treatment groups, propensity matching was applied to create comparable cohorts. RESULTS: After matching, 90 patients in the SRT and SSRT groups were selected (45 in each arm). Kaplan-Meier analysis did not show any significant differences in terms of BRFS and PFS between matched populations (p = 0.08 and p = 0.8, respectively). Multivariate models show that treatment was not associated with BRFS, neither in the whole or matched cohort, with HR of 2.15 (95%CI 0.63-7.25, p = 0.21) and 2.65 (95%CI 0.59-11.97, p = 0.21), respectively. In the matched cohort, lower rate of toxicity was confirmed for patients undergoing SSRT, with acute GI and GU adverse events reported in 4.4 versus 44.4% (p < 0.001) and 28.9 versus 46.7% (p = 0.08) of patients, and late GI and GU adverse events reported in 0 versus 13.3% (p = 0.04) and 6.7 versus 22.2% (p = 0.03) of patients, respectively. CONCLUSION: Considering the favourable therapeutic ratio of this approach and the lower number of fractions needed, SSRT should be considered as an attractive alternative to conventional SRT in this setting.

Percutaneous management of bone metastases: state of the art, interventional strategies and joint position statement of the Italian College of MSK Radiology (ICoMSKR) and the Italian College of Interventional Radiology (ICIR).

Interventional radiology provides local management of bone metastases (BM) with a palliative intent in most cases, or with a curative intent in selected patients. Its role has rapidly expanded in the last decade, offering new treatment solutions often in combination with surgery, radiation therapy and medical treatments. The aim of the present paper is to increase awareness, acceptance and adoption of interventional radiology procedures for the treatment of BM; and to present the joint position of the Italian College of Musculoskeletal Radiology and the Italian College of Interventional Radiology.

Intravesical instillations with polydeoxyribonucleotides reduce symptoms of radiation-induced cystitis in patients treated with radiotherapy for pelvic cancer: a pilot study.

PURPOSE: Chronic radiation cystitis (CRC) is a serious complication that can arise in patients with pelvic malignancies treated with radiotherapy. Polydeoxyribonucleotides (PDRNs) are known to reduce inflammation and improve tissue perfusion and angiogenesis. In this manuscript, we describe our observational experience regarding intravesical instillation of PDRNs in improving symptoms of CRC in subjects unresponsiveness to conventional medical therapy. METHODS: Eight patients with persistent and/or worsening CRC symptoms, despite conventional therapy, received biweekly intravesical instillation of PDRNs for two consecutive months. Symptoms were scored according to the Late Effects of Normal Tissues-Subjective, Objective, Management, Analytic (LENT-SOMA) scale, before, at the end, and after 4 months following the PDRNs treatment. RESULTS: Four months after instillations, a significant improvement in the subjective perception of CRC symptoms was experienced by participants. The mean LENT-SOMA score was reduced from 1.16+0.26 before to 0.34+0.035 after 4 months from instillations (p<0.001). No adverse effect related to instillations was reported. CONCLUSIONS: Subjective perception of persistent and/or worsening CRC symptoms, despite conventional therapy, is improved after intravesical instillation with PDRNs without adverse events. Even though we deduced suggestive insights, the results need to be collected and verified from a large-scale study.

Prostatectomy Bed Image-guided Dose-escalated Salvage Radiotherapy (SPIDER): An International Multicenter Retrospective Study.

BACKGROUND: Management of macroscopic local recurrence (MLR) after radical prostatectomy is a challenging situation with no standardized approach. OBJECTIVE: The objective of our study was to assess the efficacy and safety of functional image-guided salvage radiotherapy (SRT) in patients with MLR in the prostate bed. DESIGN, SETTING, AND PARTICIPANTS: In this international multicenter retrospective study across 16 European centers, eligible patients were initially treated by radical prostatectomy (RP) with or without pelvic lymph node dissection for localized or locally advanced adenocarcinoma of the prostate. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Prostate-specific antigen (PSA) measured 4 wk after RP was <0.1 ng/ml. All patients presented a biochemical relapse after RP defined by an increase in PSA level of ≥0.2 ng/ml on two successive measures. Only patients with an MLR lesion in the prostatectomy bed visualized on functional imaging (multiparametric magnetic resonance imaging, positron emission tomography/computed tomography [PET/CT] choline, or PET/CT prostate-specific membrane antigen) were eligible. Patients with lymph node, bone, or visceral dissemination at restaging imaging (CT and/or bone scintigraphy and/or magnetic resonance imaging and/or PET) were excluded. Dose escalation was defined as a dose of >66 Gy prescribed to the prostate bed or to MLR. Toxicities were classified using the Common Terminology Criteria for Adverse Events scale, version 4.03. The primary endpoint was progression-free survival (PFS). Secondary outcomes were metastasis-free survival (MPFS), biochemical progression-free survival, and overall survival. Genitourinary (GU) and gastrointestinal (GI) toxicities were analyzed. RESULTS AND LIMITATIONS: Between January 2000 and December 2019, 310 patients received at least one dose escalation on MLR and 25 patients did not receive any dose escalation. The median PSA level before SRT was 0.63 ng/ml (interquartile range [IQR], 0.27-1.7). The median follow-up was 54 mo (IQR, 50-56). Five-year PFS and MPFS were 70% (95% confidence interval [CI]: [64; 75]) and 84% (95% CI: [78; 88]), respectively. Grade ≥2 GU and GI late toxicities were observed in 43 (12%) and 11 (3%) patients, respectively. When the prescribed dose on the MLR lesion was ≥72 Gy, an improvement in 5-yr PFS was found for patients received at least one dose escalation (73% [95% CI: 65-79]) vs 60% [95% CI: 48; 70]; p = 0.03). CONCLUSIONS: In this contemporary study integrating functional imaging data, we found potential efficacy of SRT with dose escalation ≥72 Gy for patients with MLR in the prostate bed and with an acceptable toxicity profile. Prospective data exploring this MLR dose escalation strategy are awaited. PATIENT SUMMARY: In this report, we looked at the outcomes from salvage radiotherapy for prostate cancer and macroscopic relapse in a large European population. We found that outcomes varied with prostate-specific antigen at relapse, Gleason score, and dose escalation. We found potential efficacy of salvage radiotherapy with dose escalation for macroscopic relapse in the prostate bed, with an acceptable toxicity profile.

Advances in imaging and in non-surgical salvage treatments after radiorecurrence in prostate cancer: what does the oncologist, radiotherapist and radiologist need to know?

OBJECTIVES: In this article the state of art the of prostate cancer (Pca) imaging and non-surgical salvage treatments (STs) is surveyed in order to explore the impact of imaging findings on the identification of radiorecurrent Pca after external beam radiotherapy (EBRT). METHODS: A computerised search was performed to identify all relevant studies in Medline up to 2012. Additional articles were extracted based on recommendations from an expert panel of authors. RESULTS: Definitive EBRT for Pca is increasingly used as treatment. After radiorecurrent Pca, non-surgical STs are emerging and shifting from investigational status to more established therapeutic options. Therefore, several scientific societies have published guidelines including clinical and imaging recommendations, even if the timing, efficacy and long-term toxicity of these STs have to be established. In some measure, accurately delineating the location and the extent of cancer is critical in selecting target lesions and in identifying patients who are candidates for STs. However, there is increasing awareness that anatomical approaches based on measurements of tumour size have substantial limitations, especially for tumours of unknown activity that persist or recur following irradiation CONCLUSIONS: To date, the main focus for innovations in imaging is the combination of excellence in anatomical resolution with specific biological correlates that depict metabolic processes and hallmarks at the tumour level. The emergence of new molecular markers could favour the development of methods that directly determine their presence, thereby improving tumour detection. KEY POINTS: Imaging may influence therapeutic decisions during non-surgical STs. MRI findings correlate with parametric maps derived from multiple functional techniques. Non-surgical salvage treatments allow local tumour control in patients with radiorecurrent PCa.

Hypofractionated Radiotherapy in Intermediate-Risk Prostate Cancer Patients: Long-Term Results.

Background: To evaluate outcomes in terms of survival and toxicity in a series of intermediate-risk prostate cancer (PCa) patients treated with hypofractionated radiotherapy (HyRT) + hormonal therapy (HT) with or without image guidance (IGRT) and to investigate the impact of different variables. Methods: This is a multi-centric study. From January 2005 to December 2019, we treated 313 intermediate-risk PCa patients (T2b−T2c, Gleason score 7, or pre-treatment PSA 10 to 20 ng/mL) with HyRT. Patients received 54.75 Gy in 15 fractions in 5 weeks plus 9 months of neo-adjuvant, concomitant, and adjuvant HT with or without IGRT. Results: Median follow-up was 91.6 months (range 5.1−167.8 months). Median OS was not reached, and the 8- and 10-year OS was 81.9% and 72.4%, respectively. Median CSS was not reached, and the 8- and 10-year CSS was 97.9% and 94.5%, respectively. PSA at first follow-up <0.8 ng/mL was significantly related to better oncological outcomes (CSS, bRFS, LRFS, cPFS, and MFS) in both univariate and multivariate analysis. After Propensity Score matching, grade 2−3 acute and cumulative late GU (p = 0.153 and p = 0.581, respectively) and GI (p = 0.196 and p = 0.925, respectively) toxicity were not statistically different in patients treated with or without IGRT. Conclusions: HyRT is effective and safe regardless of the use of IGRT. PSA at first follow-up is an easily accessible prognostic factor that may help the clinicians to identify patients who require a treatment intensification.

Intensive multidisciplinary treatment strategies and patient resilience to challenge long-term survival in metastatic colorectal cancer: a case report in real life and clinical practice.

In fit metastatic colorectal cancer (MCRC), multidisciplinary treatment strategy integrating intensive FIr-B/FOx triplet chemotherapy associated to bevacizumab and secondary metastasectomies significantly improved clinical outcomes up to progression-free survival (PFS) 17 months and overall survival (OS) 44 months. A non-elderly woman affected by rectal cancer, lymph nodes involvement, synchronous unresectable liver metastases, was treated with first-line FIr-B/FOx integrated with two-stage liver resections, short course radiotherapy, anterior rectal resection, with a PFS 9 months and progression-free interval (PFI) 4 months off-treatment. After progression characterized by single liver and lymph node inferior mesenteric axis metastases, FIr-B/FOx was re-introduced, liver and lymph node resections were performed, with a PFS 8 months and PFI 3 months. FIr-B/FOx was further proposed due to bilateral lung, and liver metastases with stable disease, PFS 8 months. Patient experienced a limiting toxicity syndrome multiple sites (LTS-ms) with G3 diarrhea, G2 asthenia, nausea, requiring irinotecan reduction and 5-fluorouracil discontinuation, and subsequent oxaliplatin discontinuation, due to infusional hypersensitivity reaction. Overall, integrated first-line medical and surgical treatment strategies gained PFS 26 months. Further lines II-V of treatment obtained a combined PFS 28 months: modulated aflibercept/irinotecan, PFS 8 months; panitumumab, PFS 8 months, proposed due to KRAS/NRAS/BRAF wild-type and EGFR c.2156 G>C (p.G719A) mutation, achieving biomarkers reduction, lung, liver, lymph nodes partial responses; regorafenib, PFS 8 months; trifluridine-tipiracil, PFS 4 months and induced an LTS-ms, with febrile G4 leucopenia, G3 neutropenia, thrombocytopenia, asthenia, G2 anemia, diarrhea, hypotension. After 2 months of palliative care, patient died, at OS 58 months, gained by intensive medical/surgical treatments coupled with patient's resilience. To date, selection of tailored medical treatments, according to clinical (age, performance and comorbidity status) and molecular (RAS/BRAF and pharmacogenomic analyses) evaluations, careful monitoring of individual toxicity syndromes, potential integration of metastasectomies, and furthermore individual resilience as patient life priority need to challenge MCRC long-term survival.

5-Azacitidine restores and amplifies the bicalutamide response on preclinical models of androgen receptor expressing or deficient prostate tumors.

BACKGROUND: Epigenetic modifications play a key role in the in prostate cancer (Pca) progression to a hormone refractory state (HRPC) and the current use of agents targeting epigenetic changes has become a topic of intense interest in cancer research. In this regard, 5-Azacitine (5-Aza) represents a promising epigenetic modulator. This study tested the hypothesis that 5-Aza may restore and enhance the responsiveness of HRPC cells to anti-hormonal therapy on Androgen receptor (AR) expressing (22rv1) and AR-deficient (PC3) cells. METHODS: The effects were studied in vitro and in vivo models. This sequential treatment induced in vitro cell cycle arrest and apoptosis both in 22rv1 and PC3 tumor cell lines. RESULTS: This combined treatment up-regulated the expression of FasL, phospho-FADD, p16(INKA), Bax, Bak, and p21(WAF1), and inhibited FLIP, Bcl-2, and Bcl-XL expression. The re-activation of hormonal response of AR-negative PC3 cell line was partially due to the AR re-expression mediated by 5-Aza treatment. In contrast, the increase in the response to anti-androgenic therapy in 22rv1 did not correlate with AR expression levels. Furthermore, xenograft studies revealed that the combined treatment of 5-Aza with AR-antagonist Bicalutamide had additive/synergistic effects in repressing tumor growth in vivo and the underlying mechanisms responsible for these effects seem to be in part mediated by induction of apoptosis. CONCLUSIONS: So, this study strongly suggests a therapeutic potential of 5-Aza in combination with anti-androgen therapy in patients with in AR expressing and AR-deficient HRPC.

Late morbidity and oncological outcome after radical hypofractionated radiotherapy in men with prostate cancer.

OBJECTIVE: To test the hypothesis that three-dimensional hypofractionated radiotherapy (3D-HFRT) is well tolerated and not worse than 3-D conventional RT (3D-CRT) for oncological outcome. PATIENTS AND METHODS: In all, 162 men with hystologically confirmed prostate adenocarcinoma were included in the analysis. In all, 82 men were treated with 3D-HFRT (15 fractions of 3.62 Gy delivered 3 times/week; a total dose of 54.3 Gy). This group was retrospectively compared with 80 men who met the same inclusion criteria and who were treated with 3D-CRT (39 fractions of 2 Gy delivered daily; a total dose of 78 Gy). A short course of hormone therapy was administered concomitantly with the RT. RESULTS: Only one (1.7%) patient in the 3D-CRT group and two (4.0%) in the 3D-HFRT group had Grade 3 genitourinary toxicity. There was late gastrointestinal morbidity of ≥ grade 3 in only 5.1% of men treated with 3D-HFRT and in 4.0% of men treated with 3D-CRT. In both groups there was no Grade 4 toxicity. At the median (range) follow-up of 45 (39.4-51) months for the 3D-HFRT group and 57.5 (54.9-59.1) months for 3D-CRT group the progression rate was 18/82 (21.9%) and 20/80 (25.0%), respectively, with no significant worsening in the risk of biochemical failure (BCF; log-rank test, P= 0.222). CONCLUSIONS: In the present study, men with clinically localized prostate cancer had similar levels of morbidity irrespective of whether they received HFRT or CRT without any worsening in the early risk of BCF. Thus, the present data provide some clinical evidence to justify trends already emerging toward HF regimens for treating clinically localised prostate cancer.

Ablation, consolidation and radiotherapy for the management of metastatic lesions of the spine: impact on the quality of life in a mid-term clinical and diagnostic follow-up in a pilot study.

Bone metastasis in the spine are lesions that are very challenging to manage because of pain, possible respiratory and neurological complications due to the closeness with the spinal cord. In fact, a fracture of a vertebra weakened by a pathological tissue can occur. In this paper, an experience of a single center in treating bone metastasis in the vertebral soma is reported (both fractured than with an increased risk of fracture) with a combined procedure of ablation, vertebroplasty and radiotherapy. This combined strategy aims to obtain an increased ability to treat the pathological tissue (ablation and radiotherapy) and a stabilization of the osteolytic lesion (vertebroplasty). We evaluated the outcome of this procedure in 12 lesions (in 11 patients) with a follow-up (from 6 to 48 months) with clinical and imaging data. Patients showed an immediate, rapid and persistent regression of the symptomatology in all lesions except two. Moreover, a stability of the disease in the bone segment treatment was reached. Even if this is a pilot study for the number of patients and the follow-up, we believe that this approach could be promising as these early results are. In specific clinical conditions and selected patients, this study seems to be possible to perform a curative approach.

One-week vaginal brachytherapy schedule as exclusive adjuvant post-operative treatment in intermediate- and high-intermediate-risk endometrial cancer patients.

PURPOSE: The aim of the study was to report survival outcomes and toxicities incidence by using one-week vaginal brachytherapy (VBT) schedule in intermediate- and high-intermediate-risk endometrial cancer patients. MATERIAL AND METHODS: One hundred and eight patients were treated with exclusive high-dose-rate (HDR) brachytherapy short schedule (7 Gy/fraction/every other day/1 week). Acute and late rectal, urinary, and vaginal toxicities were recorded according to radiation therapy oncology group (RTOG) scores and late effects normal tissue task force - subjective, objective, management, analytic (LENT-SOMA) scores, respectively. Overall survival (OS), cause specific survival (CSS), and disease-free survival (DFS) were evaluated. RESULTS: Median follow-up was 44 months (range, 6-117 months). The 5-year OS, CSS, and DFS rates were 92.7%, 96.4%, and 89.5%, respectively. Seven of 108 (6.5%) patients relapsed after a median time of 31 months (range, 5-56 months). Death occurred in 6 patients. Four patients died for intercurrent causes without an evidence of disease. Acute bladder toxicity G1-G2 was reported in 11 of 108 (10%) patients, vaginal toxicity G1-G2 in 6 of 108 (5.5%), and gastrointestinal toxicity was observed in 3 of 108 (3%) patients. Late bladder and gastrointestinal G1 toxicities were reported in 4 of 108 (4%) and 1 of 108 (1%) patients, respectively. Late vaginal toxicity (G1-G2) was recorded in 3 of 108 (3%) cases. No grade 3-4 bladder, vaginal, and gastrointestinal toxicities were noted. CONCLUSIONS: Exclusive short course adjuvant VBT is an effective treatment in patients with early-stage endometrial cancer and provides good outcomes in terms of disease local control and DFS, with low rates of toxicity profile.

Hypovolemic shock after pelvic radiotherapy. A rare combination leading to a devastating complication.

BACKGROUND: Radiotherapy currently plays a key role in pelvic malignancies' management. Excellent outcomes have been reported on its association with chemotherapy for the treatment of the anal carcinoma. Despite that, the combined use of chemo- and radiotherapy and the high doses administered seem to be strongly associated with early and late onset side effects. METHODS: We reported a case of a 72 years old woman, affected by anal squamous cell carcinoma. She underwent chemotherapy, and then radiotherapy, with good results. RESULTS: During a regular MR control, the patient developed anaphylactic reaction to Gadolinium, and after that a rectosigmoid ischemia with total necrosis of the posterior rectal wall was diagnosed and surgically treated with Hartmann procedure. CONCLUSION: In our case we faced with the rapid and severe degeneration of pelvic anatomy determined by the sum of vascular alterations following hypovolemic shock and pelvic tissues alteration after radiotherapy. It seems essential not to underestimate the exponential outcome of a similar unusual combination of events. KEY WORDS: Anal carcinoma, Hypovolemic shock, Pelvic radiotherapy, Rectal necrosis.

Are we ready for a paradigm shift from high-dose conventional to moderate hypofractionated radiotherapy in intermediate-high risk prostate cancer? A systematic review of randomized controlled trials with trial sequential analysis.

AIM: to evaluate efficacy and late toxicity of moderate hypofractionated (HFRT) over high-dose (>76 Gy) conventional radiotherapy (CRT) in a non-inferiority perspective. METHODS: Randomized controlled trials (RCTs) were included. HFRT regimens were deemed non-inferior to high-dose CRT if the computed CI for the overall RR did not exceed the non-inferiority margin of 7%. RESULTS: When the prespecified margin, corresponding to a critical RR of 0.930 for CCS, OS and BFS, was used all efficacy outcomes satisfied the criteria for the non-inferiority analysis indicating the non-inferiority of HFRT regimens over high-dose CRT in the medium term period. Differently, the evidence concerning the late toxicity was inconclusive. CONCLUSIONS: Noninferiority analysis indicates that moderate HFRT regimes are non-inferior over high-dose CRT in the medium-term. Inconclusive is the evidence for the late toxicity. Longer follow-up will provide a more clear answer concerning the non-inferiority of HFRT regimens in the long-term period.

Dose-finding study of oxaliplatin associated to capecitabine-based preoperative chemoradiotherapy in locally advanced rectal cancer.

INTRODUCTION: Proper administration timing, dose-intensity, efficacy/toxicity ratio of oxaliplatin added to fluoropyrimidin should be improved to safely perform two-drugs intensive preoperative chemoradiotherapy in locally advanced rectal cancer (LARC). This dose-finding study investigated recommended oxaliplatin dose, safety of oxaliplatin/capecitabine regimen and preliminary activity. METHODS: Schedule: oxaliplatin dose-levels, 35-40 mg/m2/week; capecitabine 825 mg/m2/ twice daily, radiotherapy on rectum/nodes, 50/45 Gy, 45 and 9 boost/45 Gy, in first 5 and subsequent patients, 5 days/week, respectively; for 5 weeks. Pathologic complete response (pCR) 10% was projected in order to positively affect clinical outcome. RESULTS: Seventeen fit <75 years patients enrolled: median age 60; young-elderly 4 (23%); T3/T4, 15/2, N0/N1/N2, 7/9/1. At first dose-level, no dose-limiting toxicity (DLT). At second, 2 DLT, G3 mucositis, G3 thrombocytopenia, in 2/6 patients (33%). Oxaliplatin recommended dose, 40 mg/m2/week. Cumulative G3-4 toxicities: mucositis 6%, thrombocytopenia 6%. Limiting toxicity syndromes 18%, 25% in young-elderly, all single site. Objective response rate intent-to-treat 94%. Sphinter preservation 87%, pCR 6%. After 17 months follow-up, progression-free survival and overall survival were not reached. CONCLUSIONS: Oxaliplatin can be safely added to preoperative capecitabine-based chemoradiotherapy at the recommended dose 40 mg/m2/week, in LARC, with promising pCR and high activity.

Moderate Hypofractionation in Patients with Low-risk Prostate Cancer: Long-term Outcomes.

BACKGROUND/AIM: To evaluate outcomes in patients with low-risk prostate cancer treated with hypofractionated radiotherapy (HyRT). PATIENTS AND METHODS: Between April 2004 and December 2015, 175 patients with low-risk prostate cancer were treated with HyRT 60 Gy in 20 fractions with or without image guidance and reduction of margin from clinical target volume to planning target volume. RESULTS: The median follow-up was 66 months. The 8-year overall survival for the whole patient cohort was 88.9%. The 8-year biochemical no evidence of disease was higher in patients treated with image-guided HyRT (98.8% vs. 88%, p=0.023). During treatment, patients treated with image-guided HyRT presented a lower rate of grade 1-2 gastrointestinal toxicity (25.3% vs. 42.2%, p=0.001). At the last follow-up, the grade 1 Gastro-intestinal toxicity rate was 4.0% and the grade 1-2 genito-urinary toxicity rate was 25.1%. CONCLUSION: Our study demonstrated the efficacy of the schedule used with a low rate of acute and late toxicities. Therefore, reduction of margins with image-guided HyRT is safe.

Diagnostic accuracy of proton magnetic resonance spectroscopy and perfusion-weighted imaging in brain gliomas follow-up: a single institutional experience.

Objectives The objective of this study was to evaluate whether proton magnetic resonance spectroscopy and perfusion magnetic resonance imaging (MRI) are able to increase diagnostic accuracy in the follow-up of brain gliomas, identifying the progression of disease before it becomes evident in the standard MRI; also to evaluate which of the two techniques has the best diagnostic accuracy. Methods Eighty-three patients with cerebral glioma (50 high-grade gliomas (HGGs), 33 low-grade gliomas (LGGs)) were retrospectively enrolled. All patients underwent standard MRI, H spectroscopic and perfusion echo-planar imaging MRI. For spectroscopy variations of choline/creatine, choline/N-acetyl-aspartate ratio, and lipids and lactates peak were considered. For perfusion 2.0 was considered the cerebral blood volume cut-off for progression. The combination of functional parameters gave a multiparametric score (0-2) to predict outcome. Diagnostic performance was determined by the receiver operating characteristic curve, with sensitivity, specificity, positive predictive and negative predictive values. Results In patients with LGGs a combined score of at least 1 was the best predictor for progression (odds ratio (OR) 3.91) with 8.4 months median anticipation of diagnosis compared to standard MRI. The individual advanced magnetic resonance technique did not show a diagnostic accuracy comparable to the combination of the two. Overall diagnostic accuracy area under the curve (AUC) was 0.881. In patients with HGGs the multiparametric score did not improve diagnostic accuracy significantly. Perfusion MRI was the best predictor of progression (OR 3.65), with 6.7 months median anticipation of diagnosis. Overall diagnostic accuracy AUC was 0.897. Then spectroscopy and perfusion MRI are able to identify tumour progression during follow-up earlier than standard MRI. Conclusion In patients with LGGs the combination of the functional parameters seems to be the best method for diagnosis of progression. In patients with HGGs perfusion is the best diagnostic method.

Oral Platelet Gel Supernatant Plus Supportive Medical Treatment Versus Supportive Medical Treatment in the Management of Radiation-induced Oral Mucositis: A Matched Explorative Active Control Trial by Propensity Analysis.

OBJECTIVES: In this active control trial, the rate of radio-induced WHO grade 3/4 oral mucositis and the change in quality of life, assessed by OMWQ-HN, were measured in subjects with head and neck cancer treated by platelet gel supernatant (PGS) and supportive medical treatment versus subjects treated by supportive medical treatment alone. MATERIALS AND METHODS: Eighty patients with nonmetastatic head and neck cancer underwent curative or adjuvant radiotherapy. All patients underwent supportive medical treatment and/or PGS at the beginning and during radiotherapy. Sixteen patients received PGS in association with supportive medical treatment. To obtain 2 groups virtually randomized for important clinical characteristics subjects were matched, by propensity analysis, with a group of subjects (64 patients) treated with supportive medical treatment alone. RESULTS: Subjects treated with standard supportive treatment experienced significant higher WHO grade 3/4 toxicity (55%; 35/64) than subjects treated by PGS (13%; 3/16). The reduced toxicity found in PGS group paralleled with the evidence that they developed later symptoms with respect to controls. The Cox proportional hazard model indicated that patients treated with standard supportive medical treatment experienced 2.7-fold increase (hazard ratio=2.7; 95% confidence interval, 1.3-5.7) in the occurrence of WHO grade 3/4 toxicity. PGS group significantly experienced higher quality of life than control groups as measured by OMWQ-HN. A significant decrease in the opioid analgesics usage was found in the PGS group. CONCLUSIONS: These preliminary data should be interpreted with caution and could serve as a framework around which to design future trials.

Treatment of osteolytic solitary painful osseous metastases with radiofrequency ablation or cryoablation: A retrospective study by propensity analysis.

The present study aimed to measure the improvement in pain relief and quality of life in patients with osteolytic solitary painful bone metastasis treated by cryoablation (CA) or radiofrequency ablation (RFA). Fifty patients with solitary osteolytic painful bone metastases were retrospectively studied and selected by propensity analysis. Twenty-five patients underwent CA and the remaining twenty-five underwent RFA. Pain relief, in terms of complete response (CR), the number of patients requiring analgesia and the changes in self-rated quality of life (QoL) were measured following the two treatments. Thirty-two percent of patients treated by CA experienced a CR at 12 weeks versus 20% of patients treated by RFA. The rate of CR increased significantly with respect to baseline only in the group treated by CA. In both groups there was a significant change in the partial response with respect to baseline (36% in the CA group vs. 44% in the RFA group). The recurrence rate in the CA and RFA groups was 12% and 8%, respectively. The reduction in narcotic medication requirements with respect to baseline was only significant in the group treated by CA. A significant improvement in self-rated QoL was observed in both groups. The present study seems to suggest that CA only significantly improves the rate of CR and decreases the requirement of narcotic medications. Both CA and RFA led to an improvement in the self-rated QoL of patients after the treatments. However, the results of the present study should be considered as preliminary and to serve as a framework around which future trials may be designed.

Bone targeted therapy for preventing skeletal-related events in metastatic breast cancer.

Cancer cells can alter physiological mechanisms within bone resulting in high bone turnover, and consequently in skeletal-related events (SREs), causing severe morbidity in affected patients. The goals of bone targeted therapy, as bisphosphonates and denosumab, are the reduction of incidence and the delay in occurrence of the SREs, to improve quality of life and pain control. The toxicity profile is similar between bisphosphonates and denosumab, even if pyrexia, bone pain, arthralgia, renal failure and hypercalcemia are more common with bisphosphonates, while hypocalcemia and toothache are more frequently reported with denosumab. Osteonecrosis of the jaw (ONJ) occurred infrequently without statistically significant difference. The present review aims to provide an assessment on bone targeted therapies for preventing the occurrence of SREs in bone metastatic breast cancer patients, critically analyzing the evidence available so far on their effectiveness, in light of the different mechanisms of action. Thus, we try to provide tools for the most fitting treatment of bone metastatic breast cancer patients. We also provide an overview on the usefulness of bone turnover markers in clinical practice and new molecules currently under study for the treatment of bone metastatic disease.