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Prostatectomy, radiotherapy and watchful waiting are the main therapeutic options available for local stage of prostate cancer (PCa). We report our experience on 394 patients affected by prostate cancer primarily treated with high-dose, image-guided, IMRT, focusing on gastrointestinal, genitourinary toxicities and biochemical control. From July 2003 to August 2014, 394 patients were treated with radical high-dose radiotherapy (HDRT) for prostate cancer; the mean total radiation dose was 79 Gy in standard fractions. Hormonal therapy (HT) was administered to 7.6% of low-risk patients, to 20.3% of intermediate-risk patients and to 72% of high-risk patients. Patients were evaluated for biochemical failure, local recurrence (LR) and metastases. Ninety-seven patients (26.65%) developed acute GU toxicity at the medium dose of 25.4 Gy, grade 1 (G1) or grade 2 (G2) in 94 cases. Only 16 patients (4.06%) reported chronic GU toxicity (G1 or G2), and one case developed G3 cystitis. No G3 GI acute and late toxicity were detected. Fifty-six (14.2%) patients experienced LR, 26 (6.6%) developed metastases and 70 patients (17.8%) were deceased. Gleason sum score > 7 was predictive for worse overall survival (GS = 7 was borderline) and for metastasis. No factors resulted predictive for local relapse. HT pre-RT had been demonstrated as a negative predictor for OS and DFS-DM. Data confirm the safety of HDRT for PCa. Treatment was efficient with low toxicity profile. Moreover, continued technologic advancements, as image-guided radiotherapy, could lead to further reduction in toxicity, thus increasing the therapeutic index.

Background Moderately hypofractionated radiotherapy (RT) currently represents the standard RT approach for all prostate cancer (PCa) risk categories. We performed a systematic review and meta-analysis of available literature, focusing on acute and late genitourinary (GU) and gastrointestinal (GI) adverse events (AEs) of moderate hypofractionation for localized PCa. Materials and methods Literature search was performed and two independent reviewers selected the records according to the following Population (P) Intervention (I) Comparator (C) and Outcomes (O) (PICO) question: “In patients affected by localized PCa (P), moderately hypofractionated RT (defined as a treatment schedule providing a single dose per fraction of 3–4.5 Gy) (I) can be considered equivalent to conventionally fractionated RT (C) in terms of G > 2 GI and GU acute and late adverse events (O)?”. Bias assessment was performed using Cochrane Cochrane Collaboration's Tool for Assessing Risk of Bias. Results Thirteen records were identified and a meta-analysis was performed. Risk of acute GI and GU > 2 adverse events in the moderately hypofractionated arm was increased by 9.8 % (95 %CI 4.8 %–14.7 %; I2 = 57 %) and 1.5 % (95 % CI -1.5 %-4.4 %; I2 = 0%), respectively. Discussion Overall, majority of trials included in our meta-analysis suggested that moderately hypofractionated RT is equivalent, in terms of GI and GU adverse events, to conventional fractionation. Pooled analysis showed a trend to increased GI toxicity after hypofractionated treatment, but this might be related to dose escalation rather than hypofractionation.

Proton therapy could minimize the risk of side effects and, therefore, reduce the possible detrimental effect on health-related quality of life (HRQOL) of re-irradiation. The aim of this study was to determine the effect of re-irradiation with active scanning proton therapy on recurrent glioblastoma (GBM) in terms of HRQOL scored by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30 and EORTC Quality of Life Questionnaire Brain Cancer Module (QLQ-BN20). Thirty-three patients with recurrent GBM were re-irradiated with active scanning proton therapy. Subscales within the EORTC QLQ-C30 include five functional scales, six single-item scales, and global QoL. The BN20 assessed visual disorders, motor function, communication deficit, various disease symptoms, treatment, toxicity, and future uncertainty. The patients completed the questionnaires before starting proton therapy, the last day of proton therapy, and at every follow-up visit until progression of disease. The treatment was associated with improvement or stability in most of the preselected HRQOL domains. Global health improved over time with a maximum difference of six points between baseline and 3-months follow-up. Social functioning and motor dysfunction improved over time with a maximum difference of eight and two points, respectively. We showed a non-significant decrease in cognitive and emotional functioning. Fatigue remained stable during the analysis such as the other preselected domains. Re-irradiation with proton therapy is a safe and effective treatment in patients with recurrent glioblastoma. Proton therapy does not negatively effect on HRQOL, but rather it seems to preserve HRQOL until the time of disease progression.

Introduction: The prognosis of glioma is dismal, and almost all patients relapsed. At recurrence time, several treatment options are considered, but to date there is no a standard of care. The Neurooncology Study Group of the Italian Association of Radiation Oncology (AIRO) collected clinical data regarding a large series of recurrent glioma patients who underwent re-irradiation (re-RT) in Italy. Methods: Data regarding 300 recurrent glioma patients treated from May 2002 to November 2017, were analyzed. All patients underwent re-RT. Surgical resection, followed by re-RT with concomitant and adjuvant chemotherapy was performed. Clinical outcome was evaluated by neurological examination and brain MRI performed, 1month after radiation therapy and then every 3months. Results: Re-irradiation was performed at a median interval time (IT) of 16months from the first RT. Surgical resection before re-RT was performed in 19% of patients, concomitant temozolomide (TMZ) in 16.3%, and maintenance chemotherapy in 29%. Total doses ranged from 9Gy to 52.5Gy, with a median biological effective dose of 43Gy. The median, 1, 2year OS were 9.7months, 41% and 17.7%. Low grade glioma histology (p ≪ 0.01), IT > 12months (p = 0.001), KPS > 70 (p = 0.004), younger age (p = 0.001), high total doses delivered (p = 0.04), and combined treatment performed (p = 0.0008) were recorded as conditioning survival. Conclusion: our data underline re-RT as a safe and feasible treatment with limited rate of toxicity, and a combined ones as a better option for selected patients. The identification of a BED threshold able to obtain a greater benefit on OS, can help in designing future prospective studies.

Background The tumors of many patients with prostate cancer eventually become refractory to androgen deprivation therapy with progression to metastatic castration-resistant disease. Significant advances in the treatment of metastatic castration-resistant prostate cancer (mCRPC) have been made in recent years, and new treatment strategies have recently been made available. The aim of this report was to schematically review all the approved pharmacologic treatment options for patients with mCRPC through 2018, analyzing the efficacy and possible side effects of each therapy to assist clinicians in reaching an appropriate treatment decision. New biomarkers potentially of aid in the choice of treatment in this setting are also briefly reviewed. Methods We performed a literature search of clinical trials of new drugs and treatments for patients diagnosed with mCRPC published through 2018. Results Two new hormonal drugs, abiraterone acetate and enzalutamide have been approved by FDA in 2011 and 2012, respectively for the treatment of patients with mCRPC and have undergone extensive testing. While these treatments have shown a benefit in progression-free and overall survival, the appropriate sequencing must still be determined so that treatment decisions can be made based on their specific clinical profile. Cabazitaxel has been shown to be an efficient therapeutic option in a postdocetaxel setting, while its role in chemotherapy-naive patients must still be determined. Sipuleucel-T and radium-223 have been studied in patients without visceral metastases and have achieved overall survival benefits with good safety profiles. The feasibility and efficacy of combinations of new treatments with other known therapies such as chemotherapy are currently under investigation. Conclusions Drug development efforts continue to attempt to prolong survival and improve quality of life in the mCRPC setting, with several therapeutic options available. Ongoing and future trials are needed to further assess the efficacy and safety of these new drugs and their interactions, along with the most appropriate sequencing.

The aim of our Phase II study is to demonstrate the benefits, safety, and tolerance of Orasol Plus, an easy and feasible Lapacho-based medication. Orasol Plus is a nutritional, swallowable solution, useful to support the defenses of the oropharyngeal mucosa. Between January and June 2014, 40 consecutive adult patients affected by head and neck cancer were enrolled. Orasol Plus was administered 3 times a day from the first day till the end of radiotherapy. Primary endpoint was to evaluate tolerance and safety of Orasol Plus; secondary endpoint was to evaluate the effect of Orasol Plus on the incidence of treatment discontinuation. Nearly all patients used Orasol Plus easily till the end of radiotherapy without interruptions. Only 11 (27.5%) patients developed oral mucositis (OM) Grade 2 and only 4 (10%) patients OM Grade 3, no patient developed OM Grade 4. No patient discontinued radiotherapy because of OM. Orasol Plus was well tolerated and the compliance of patients was optimal, mainly due to the fact that it can be swallowed. Data from our study are encouraging and they need to be confirmed by a Phase III study.

Elevated pre-treatment lymphocyte (L) to monocyte (M) ratio (LMR) in peripheral blood has been suggested to correlate with improved survival in some malignancies, but data in the context of pancreatic cancer (PC) is limited. The aim of this study was to evaluate the prognostic significance of LMR before, during and after definitive chemoradiotherapy (CRT) for locally advanced pancreatic cancer (LAPC).We retrospectively reviewed 57 patients with LAPC treated with definitive CRT at a single institution from 2005 to 2013. Complete blood counts were obtained before (TP1), during the third week (TP2) and at the end of CRT (TP3). Univariate analysis (UVA) included gender, age, body mass index, pre-treatment CA19-9, T stage, N stage, induction chemotherapy (ICT), absolute L count (TP1, TP2, TP3), absolute M count (TP1, TP2, TP3), LMR (TP1, TP2, TP3), and relative LMR changes (TP2 ÷ TP1, TP3 ÷ TP1, TP3 ÷ TP2).Median follow-up was 14 months. Twelve patients received ICT. Median LMR was 2.7 (range, 0.8-5.25), 1.4 (range, 0.3-5) and 0.98 (range, 0.3-3.4) at TP1, TP2 and TP3, respectively. Superior PFS was significantly associated with an absolute M count during CRT0.1 (P=0.04) while pre-CRT L count ≥1.1 trended towards significance (P=0.09). Superior OS was significantly associated with change in LMR (TP3 ÷ TP2)0.32 (P0.0001) while pre-CRT LMR ≥2.6 trended towards significance (P=0.06).Factors significantly associated with overall survival (OS) and progression-free survival (PFS) were change in LMR at the end of CRT and absolute M count during CRT. This analysis suggests treatment-time-specific immune system parameters may affect clinical outcomes and warrant continued investigation.

Introduction: Target volume definition is of critical relevance when re-irradiation is delivered and steep dose gradient irradiation techniques, such as proton therapy (PT), are employed. Aim of the study is to investigate the impact of 18F-DOPA on target volume contouring in recurrent glioblastoma (rGBM) patients (pts) undergoing re-irradiation with PT. MATERIAL AND METHODS: We investigated the differences in volume and relationship of magnetic resonance imaging (MRI)- vs. DOPA PET-derived gross tumor volumes (GTVs) of 14 rGBM pts re-irradiated with PT between January and November 2016. All pts had been previously treated with photon radiotherapy (60 Gy) with concomitant and adjuvant temozolomide. All the pts received morphological MRI with contrast enhancement medium administration and 18F-DOPA PET-CT study. We used the pathological distribution of 18F-DOPA in brain tissue to identify the so-called Biological Tumor Volume (BTV). Such areas were assessed using a tumor to normal brain ratio > 2. Moreover, any area of contrast enhancement on MRI was used to identify the MRI-based GTV (MRGTV). Definitive GTV included MRGTV plus BTV. Clinical target volume was generated by adding to GTV a 3-mm uniform margin manually corrected in proximity of anatomical barriers. CTV was expanded by 4 mm to create planning target volume. All pts received 36 GyRBE in 18 fractions. Mean values of differently delineated GTVs were compared each other by paired Student’s t-test; p < 0.05 was considered significant. To further compare MRGTV and BTV, the overlapping (MRGTV ^ BTV) and the composite (MRGTV U BTV) volumes were calculated, and a concordance index (CI) was defined as the ratio between the overlap and composite volumes. Results: MRGTV (mean 14.9 ± 14.5 cc) was larger than BTV (mean 10.9 ± 9.8 cc) although this difference was not statistically significant. The composite volume (mean 20.9 ± 14.7 cc) was significantly larger than each single volume (p < 0.006). The overlapping volume (mean 5.7 ± 3.3 cc) was quite small compared to each single volume and suggest that relevant part of MRIGTV is not covered by BTV as well as that relevant part of BTV is not covered by MRGTV. In line with such results we recorded also a low CI (mean 0.26 ± 0.2). The PT irradiation of PET-integrated target volumes provided a median progression-free survival (PFS) of 6 months, while the 6-month PFS rate was 57%; median survival after PT was 8.7 months, while 9-month survival rate was 60%. Conclusions: Target volume definition for rGBM undergoing PT re-irradiation may yield significantly differing results depending upon the imaging modality used for target contouring. Our data suggest that 18F-DOPA PET can detect relevant non-enhancing pathological areas outside the conventional MRGTV ultimately yielding to larger volumes to be irradiated. Influence on clinical outcomes deserves further evaluation.

Chordoma is a slow-growing neoplasm arising from remnants of the embryonic notochord. Surgery is recognized as the gold standard approach, however gross total resection is rarely possible for this reason most patients undergo subtotal resection or biopsy followed by radiotherapy. Myasthenia gravis (MG) is neuromuscular autoimmune disorder .The feasibility and safety of radiotherapy and especially of proton therapy (PT) in patients affected by MG has never been adequately documented. We report the case of a patient with lumbar chordoma who was diagnosed of MG just at the beginning of PT.

BACKGROUND Stereotactic radiosurgery (SRS) is an important treatment option for intracranial lesions and several photon-SRS techniques have been developed. Proton therapy (PT) has special characteristics that allow normal tissues to be spared better as well as greater homogeneity than with the use of photons, but limited data are available for proton-SRS. Nowadays, PT-SRS is delivered only with passive scattering technique while active pencil beam scanning (PBS) that is considered the most advanced proton technique has not been reported for SRS treatments yet. Here we report early clinical outcomes of PBS PT SRS. MATERIAL AND METHODS Between June 2017 and January 2019, 14 patients (pts) with 20 lesions underwent PBS PT SRS at our institution. Median age was 62 years (range, 28–87). Median Karnofsky performance status was 90 (range, 70–100). Six were male. Tumors included 16 meningiomas (MG) and 4 vestibular schwannomas (VS). Median GTV was 1.05 cc (range, 0.2–2.71). Dose prescription was 12 Gy radiobiologic equivalent (RBE) in one fraction for VS and 15 GyRBE in one fraction for MG. Pts were immobilized using a frameless system: Type-S proton overlay and Type-S proton mask (CIVCO medical solutions, Kalona, IA, USA) together with Moldcare headrest (Q-Fix systems, Avondale, PA, USA). All pts were treated with PBS PT using 2–3 fields with single field optimization technique, and using min-max robust robust optimization (2 mm setup errors, 3.5% range uncertainties), with a Monte Carlo algorithm and 1 mm grid size. Toxicity was assessed using Common Terminology Criteria for Adverse Events version 4.0. RESULTS Median follow-up (FU) was 9 months (range, 3–22). All pts completed the treatment with excellent compliance and no side effects were registered during the procedure. Registered acute side effects include grade 1 (14%) fatigue, grade 2 (7%) headache, and grade 2 (28%) alopecia. There were no grade 3 or higher acute toxicities. Registered late side effects include grade 1 (7%) headache, and grade 1 (14%) alopecia. There were no grade 3 or higher late toxicities. Currently, absolute tumor control is 100% regardless the type of tumor. Despite the short FU radiological reduction was registered in 9 lesions (45%). CONCLUSION PBS PT SRS is a feasible and safe treatment in pts with MG or VS. A high radiological response rate was observed. Longer FU is necessary to assess definitive safety and efficacy.

We report the case of a man affected by renal cell carcinoma with vertebral metastases, who presented a radiological complete response after systemic treatment with everolimus.

BACKGROUND: Protontherapy (PT) could minimize the risk of side effects compared to conventional photon therapy and therefore reduce the possible detrimental effect on QoL of re-irradiation. We report the effect of re-irradiation with active scanning PT of recurrence GBM in terms of quality of life scored by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)--C30 and EORTC Quality of Life Questionnaire Brain Cancer Module (QLQ-BN20) MATERIAL AND METHODS: Between January 2015 and May 2018 twenty-eight patients with recurrence GBM were re-irradiated with active scanning PT. All patients had been previously treated with photon radiotherapy (60 Gy) with concomitant and adjuvant temozolomide (TMZ). Median age and Karnofsky performance status at re-irradiation were 53 years (range, 30–68 years) and 80%, (range, 60–100%), respectively. Target definition was based on CT, MR, and 18F-DOPA PET imaging. All patients received 36 GyRBE (RBE: relative biologic effectiveness) in 18 fractions, with concomitant TMZ in 7 patients (25%). Subscales within the EORTC QLQ-C30 include five functional scales (physical, role, emotional, cognitive, and social), three symptoms scales (nausea, vomiting, and fatigue), six single-item scales (insomnia, appetite loss, constipation, diarrhea, dyspnea, and financial effect of tumor/treatment) and global QoL. The BN20 is specifically developed for brain patients and assessed visual disorders, motor function, communication deficit, various disease symptoms, treatment, toxicity and future uncertainty. The patients completed the EORTC questionnaires before starting PT, the day of the end of PT and every follow-up consult (1-month, 3-months) until progression of disease. RESULTS: Twenty-six patients completed the questionnaires at baseline until progression of disease. The treatment was associated with improvement or stability in most of the preselected HRQOL domains. Global health improved over time with a maximum difference of 6 points between baseline and 3-months follow-up. Social functioning and motor dysfunction improved over time with a maximum difference of 8 and 2 points, respectively. We showed only a small not significance decrease in cognitive and emotional functioning. Interestingly, fatigue remained stable during the analysis such as the other preselected domains. CONCLUSION: Re-irradiation with PT is a safe treatment without a negative effect on HRQOL until the time of disease progression.

BACKGROUND: To report preliminary results of active beam scanning proton therapy (PT) for large skull base benign meningiomas. MATERIAL AND METHODS: Thirty-three patients (pts) with large skull base meningiomas were treated with PT between January 2015 and February 2018. Median age was 53 years (range, 28–82) while KPS ranged between 60 and 100 (median 90); 26 were female (79%), and 7 were male (21%). Twelve pts (36%) had histologically proven World Health Organization (WHO) Grade I tumors. In remaining pts diagnosis was based on the typical imaging appearance of benign meningioma. All patients received PT for residual, progressive or non-operable lesions. Newly diagnosed tumors received total dose of 50 GyRBE (RBE: relative biologic effectiveness) while progressing meningiomas 54 GyRBE. All the treatments were delivered at 2 GyRBE per fraction. Treatment planning was based on morphological magnetic resonance imaging (MRI) with contrast enhancement medium administration. All pts received also 68-Ga-DOTATOC-PET. Any area of contrast enhancement on MRI was used to identify the gross tumor volume. We used the pathological distribution of 68Ga-DOTATOC in brain tissue to identify the so-called Biological Tumor Volume. Gross tumor volume ranged from 21 to 107 cc. Toxicity was assessed according to Common Terminology Criteria for Adverse Events version 4.0. Median follow-up time was 9 months (range, 3–37). RESULTS: All pts completed the treatment without breaks. Acute side effects include grade 1 (21%) and grade 2 (9%) skin erythema, grade 1 (9%) and grade 2 (9%) alopecia, grade 1 (48%) fatigue, grade 1 (6%) and grade 2 (15%) conjunctivitis, grade 1 (15%) pain, grade 1 (15%) blurred vision, grade 1 (15%) headache, and grade 2 (15%) skin hyperpigmentation. One pt experienced grade 3 pain. There were no further grade 3 or higher acute toxicities. Late side effects include grade 1 (9%) and grade 2 (9%) alopecia, grade 1 (21%) fatigue, grade 1 (9%) and grade 2 (6%) headache, grade 1 (6%) dizziness, grade 1 (6%) blurred vision, grade 1 (6%) and grade 2 (6%) pain, grade 1 (6%) dry eye, and grade 1 (15%) skin hyperpigmentation. One pts experienced grade 3 pain. There were no further grade 3 or higher late toxicities. One pts (3%) with cavernous sinus meningioma experienced complete obstruction of intracavernous carotid artery with mild transient symptoms that resolved in few days and brain tissue ischemia detected at MRI (grade 2). Before irradiation this pts already had a meningioma-related near-complete obstruction of the intracavernous carotid artery and received a vascular surgery evaluation. Currently, absolute tumor control is 100%. Moreover, relief of symptoms recorded before irradiation occurred in 24% of pts. CONCLUSION: PT is feasible and safe treatment for pts with large skull base benign meningiomas. Longer follow-up is necessary to assess definitive efficacy.

10-year data from the European Organisation for Research and Treatment of Cancer trial 22911 have been published, reigniting the debate regarding postoperative radiotherapy for prostate cancer. These data show that adjuvant radiotherapy significantly improves biochemical progression-free survival and local control compared with a 'wait-and-see' policy, supporting the 5-year follow-up data.

Breast angiosarcomas (BAs) are rare but serious events that may arise after radiation exposure. Disease outcome is poor, with high risk of local and distant failure. Recurrences are frequent also after resection with negative margins. The spectrum of vascular proliferations associated with radiotherapy in the setting of breast cancer has expanded, including radiation-associated atypical vascular lesions (AVLs) of the breast skin as a rare, but well-recognized, entity. Although pursuing a benign behavior, AVLs have been regarded as possible precursors of postradiation BAs. We report an unusual case of a 71-year-old woman affected by well-differentiated bilateral cutaneous BA, diagnosed 1.9 years after adjuvant RT for synchronous bilateral breast cancer. Whole-life clinical followup is of crucial importance in breast cancer patients.

The dislocation of the malignant cells along the needle tract during breast cancer (BC) diagnosis has been demonstrated by several studies. However, the published experiences that relate the diagnostic technique with sentinel node (SN) involvement are few and controversial. The aim of our analysis was to evaluate the impact of different techniques for preoperative BC biopsy among prognostic factors of metastases occurrence in SN.We reviewed the institutional clinical database of our Center. A total of 674 patients were diagnosed between February 1999 and December 2006 with invasive BC. SN metastases classification followed the 2002 American Joint Committee on Cancer (AJCC) TNM pathological staging: macrometastases, micrometastases, isolated tumor cells or negative. Only macrometastases and micrometastases were considered positive. Concerning fine-needle aspiration cytology, we used disposable needles of the size of 21-27 G. For percutaneous biopsy we used cutting needle type "tru-cut"; the Gauge needle ranged between 14 and 20.At univariate analysis of specific parameters using positive SN as outcome, percutaneous diagnostic technique did not affect significantly the SN positivity (p = 0.60). At multivariate models only central quadrant lesion (p = 0.005) and lymph vascular invasion (LVI) presence (p 0.0001) maintained the statistical significance as risk factor for positive SN status. Polytomic logistics models showed that only LVI maintained the statistical significance both for prediction of micrometastases and macrometastases.Our analysis showed that different techniques used for BC diagnosis did not influence SN status.