Docetaxel Provides Oncological Benefits in the Era of New-Generation Androgen Receptor Inhibitors - or Is Three a Crowd?

In recent years, several systemic therapies have been introduced for metastatic hormone-sensitive prostate cancer, including androgen deprivation therapy (ADT) combined with docetaxel (Doc) and/or new-generation androgen receptor signaling inhibitors (ARSI). Trials evaluating ADT + ARSI have consistently demonstrated an overall survival (OS) benefit for doublet therapy over ADT alone. Similarly, the STOPCaP meta-analysis showed an OS benefit in favor of ADT + Doc versus ADT alone. ARSI, Doc, and ADT have different antitumor mechanisms, thus potentiating the effect of combination therapy. Two randomized trials showed that the addition of ARSI to ADT + Doc improves OS, especially for synchronous high-volume disease. However, the real question about triplet therapy remains unanswered: whether combining Doc with ARSI improves outcomes compared to ADT + ARSI. As there are no head-to-head comparisons, this narrative review aims to summarize the current evidence regarding triplet therapy versus doublet therapy including ADT+ ARSI.

Prospective multicentre analysis of the therapeutic approach and prognostic factors determining overall survival in elderly patients with non-small-cell lung carcinoma treated with curative intent.

Objective: To analyse patterns of treatment with curative intent commonly used in elderly patients with locally advanced non-small-cell lung carcinoma (NSCLC) and predictive factors of overall survival in routine clinical practice. Methods: This multicentre prospective study included consecutive patients aged ≥65 years old diagnosed with NSCLC between February 2014 and January 2018. Inclusion criteria: age ≥65 years, stage IIIA/IIIB NSCLC. Treatment decisions were taken by a multidisciplinary committee. Kaplan-Meier curves and log-rank test were used to identify which clinical/treatment-associated variables, or pre-treatment quality of life (QOL) considering EORTC QLQ-C30 (and LC13 module) were predictive of overall survival. Results: A total of 139 patients were recruited. Median follow-up was 9.9 months (1.18-57.36 months) with a median survival of 14 months (range 11-17 months). In the group>75-year-old patients, the committee recommended chemotherapy and sequential radiotherapy (55.6%) or radiotherapy alone (22.2%), rather than surgery (3.7%) or concomitant radiochemotherapy (16.5%). However, in 65- to 75-year-old patients, surgery and concomitant radiochemotherapy were recommended in half of cases (p=0.003). Regarding multivariate analysis, the risk of death was higher in patients with pre-existing heart disease (p=0.002), low score for physical functioning (p=0.0001), symptoms of dysphagia (p=0,01), chest pain (p=0.001), and those not undergoing surgical treatment (p=0.024). Conclusions: Patients >75 years received more conservative treatments. Surgery improved survival and should be carefully considered, regardless of patient age. Comorbidities and poor baseline QOL are predictive of shorter survival. Advances in knowledge: Measuring these parameters before treatment may help us to define a population of frail patients with a poorer prognosis to facilitate decision making in clinical practice.

Bone health and therapeutic agents in advanced prostate cancer.

Prostate cancer is the most frequent genitourinary tumor worldwide. Maintaining an optimum bone health throughout the natural course of prostate cancer is an important aspect in the management of this disease, particularly in this at risk population of older and frail patients who experience bone loss related to androgen-deprivation therapy (ADT) and/or patients who develop bone metastases. The number of treatment options for advanced prostate cancer that combine ADT with docetaxel, new hormonal agents and/or radiotherapy has increased substantially in recent years. Bisphosphonates and other bone targeted agents such as denosumab have shown an improvement in bone mineral density and are suited for patients with treatment-related osteoporosis and/or bone metastases with an increased risk of skeletal-related events (SREs). In this context, the aim of this review is to analyse key aspects of bone health and therapies that can prevent the occurrence of SREs throughout the clinical course of prostate cancer, and how to combine them with new available treatments in this setting.

MRI-guided focal boost to dominant intraprostatic lesion using volumetric modulated arc therapy in prostate cancer. Results of a phase II trial.

OBJECTIVE: To determine morphological and biological control as well as toxicity and quality of life (QoL) of men with localized prostate cancer (PCa) treated with MRI-guided focal boost radiotherapy. MATERIAL AND METHODS: 30 patients with PCa and a visible dominant intraprostatic lesion (DIL) identified on mpMRI were included in a prospective Phase II trial. Matching point registration of planning CT and T2W, diffusion-weighted and a gradient-recalled echo (GRE) MRI images made in treatment position was used for prostate and tumour delineation. Treatment consisted on 35 daily fractions of 2.17 Gy with a concomitant focal boost to the DIL of 2.43 Gy using volumetric modulated arc therapy (VMAT) and image-guided radiation therapy (IGRT) with intraprostatic fiducial markers. Biochemical failure was analysed using PSA nadir +2 ng/mL criteria and local control using mpMRI evaluation at 6-9 months following RT. Acute and late toxicity were defined according to CTCAE v.4.0 and RTOG/EORTC scales and QoL was assessed using IPSS, EPIC short-form and UCLA-PCI questionnaires. RESULTS: The median radiation dose to the prostate was 77.6 Gy (IQR 77.3-78.1), and to the DIL was 85.5 Gy (IQR 85.0-86.0). With a median follow up of 30.0 months (IQR 25.5-40.27), all patients remain free of biochemical relapse. An mpMRI complete response was observed in 25 patients during the first post-treatment evaluation at 6 months. The remaining five patients achieved a complete disappearance of the DIL both on T2 and DWI on the second mpMRI performed at 9 months following treatment. Six out of 30 (20%) patients presented acute Grade 2 urinary toxicity with no Grade 3 acute complications. Acute rectal toxicity was only found in 2 (6.6%) patients (both Grade 1). Only late Grade 1 urinary and rectal complications were observed in 3/30 patients, respectively, with no Grade 2 or more late toxicity. The urinary, bowel and sexual bother EPIC scores were slightly and insignificantly increased in the first 3 months post-treatment, returning to normal afterwards. CONCLUSIONS: mpMRI-guided focal boost using VMAT hypofractionated technique is associated with an excellent morphological and functional response control and a safe toxicity profile. ADVANCES IN KNOWLEDGE: In the present trial, we examined the potential role of mpMRI for radiological assessment (functional and morphological) of treatment response in high-risk prostate cancer patients treated with MRI-guided focal radiotherapy dose intensification to dominant Intraprostatic lesion.

Salvage local treatment for localized radio-recurrent prostate cancer: a narrative review and future perspectives.

Although dose escalation protocols have improved biochemical control in prostate cancer radiotherapy, 10-45% of patients will experience disease recurrence. The prostate and seminal vesicles are the most frequent site of the first relapse. Traditionally, these patients have been managed with hormonal therapy, which is not curative. Recent improvements in diagnostic tests (e.g., multiparametric magnetic resonance and molecular imaging, including PET/CT scan with choline or Ga-PSMA) and new treatment techniques (e.g., stereotactic body radiation therapy or other minimally invasive alternatives like high-intensity focus ultrasound, cryoablation or high-dose-rate brachytherapy) offer new therapeutic strategies with the potential to cure some patients with limited adverse effects. In this narrative review, the authors present the most recent evidence to help identify the most suitable candidates for salvage treatment.

Salvage brachytherapy for locally recurrent prostate cancer after single-fraction 19 Gy high-dose-rate brachytherapy: toxicity, prostate-specific antigen kinetics, and cancer control.

PURPOSE: To evaluate toxicity, prostate-specific antigen (PSA) kinetics, and cancer control of high-dose-rate brachytherapy (HDR-BT) as a salvage modality for men with locally recurrent prostate cancer, after primary HDR-BT failure. MATERIAL AND METHODS: Twelve patients with biochemical failure and a local relapse after 19 Gy single-fraction high-dose-rate brachytherapy (HDR-BT 19 Gy) were salvaged using two HDR-BT fractions. Salvage treatment consisted of two HDR-BT applications, one week apart, delivering 12 Gy to the prostate per application (HDR-BT 12 × 2). RESULTS: Median age and initial PSA prior to rescue treatment were 74 years (range, 65-80) and 5.29 ng/ml (range, 2.37-16.40), respectively. Forty-two percent had a low-risk and 58% presented with intermediate-risk prostate cancer. Median follow-up period was 26 months (range, 10-42). Median time to PSA nadir was 12 months, with a median value of 0.21 ng/ml. Most of the patients (11 of 12) achieved a PSA decline ≥ 90%. Acute grade 2 genitourinary (GU) toxicity occurred in 4 patients (33.3%) and none presented with acute gastrointestinal (GI) toxicity. Two patients (16.7%) suffered from late GU grade 2 toxicity. No grade 3 toxicity were recorded. To date, 2 patients (16.7%) have experienced biochemical failure after salvage treatment. CONCLUSIONS: Salvage HDR-BT 12 × 2 is a feasible and well-tolerated treatment, with acceptable toxicity rates for men with locally recurrent prostate cancer, who failed after HDR-BT with 19 Gy. Moreover, PSA kinetics and cancer control after salvage treatment suggest that this strategy might be efficacious in this clinical setting.

Oligometastatic Prostate Adenocarcinoma. Clinical-Pathologic Study of a Histologically Under-Recognized Prostate Cancer.

The clinical parameters and the histological and immunohistochemical findings of a prospective protocolized series of 27 prostate carcinoma patients with oligometastatic disease followed homogeneously were analyzed. Lymph nodes (81.5%) and bones (18.5%) were the only metastatic sites. Local control after metastatic directed treatment was achieved in 22 (81.5%) patients. A total of 8 (29.6%) patients developed castration-resistant prostate cancer. Seventeen (63%) patients presented with non-organ confined disease. The Gleason index 8-10 was the most frequently observed (12 cases, 44.4%) combined grade. Positive immunostainings were detected with androgen receptor (100%), PGP 9.5 (74%), ERG (40.7%), chromogranin A (29.6%), and synaptophysin (18.5%) antibodies. The Ki-67 index value > 5% was observed in 15% of the cases. L1CAM immunostaining was negative in all cases. Fisher exact test showed that successful local control of metastases was associated to mild inflammation, organ confined disease, Ki-67 index < 5%, and Gleason index 3 + 3. A castration resistant status was associated with severe inflammation, atrophy, a Gleason index higher than 3 + 3, Ki-67 index ≥ 5%, and positive PGP 9.5, chromogranin A, and synaptophysin immunostainings. In conclusion, oligometastatic prostate adenocarcinoma does not have a specific clinical-pathologic profile. However, some histologic and immunohistochemical parameters of routine use may help with making therapeutic decisions.

Pain response and quality of life assessment in patients with moderate/severe neuropathic pain due to bone metastasis undergoing treatment with palliative radiotherapy and tapentadol: A prospective multicentre pilot study.

INTRODUCTION: To assess pain response rate (RR) and quality of life (QoL), in patients with moderate/severe neuropathic pain (NP) due to bone metastasis (BM) undergoing palliative 3D radiotherapy plus tapentadol. METHODS: We conducted a prospective multicentre pilot study. Patients were assessed before radiotherapy using the validated questionnaire (Douleur Neuropathique en 4 questions). Response to radiotherapy (8 Gy-30 Gy/1-10fr) at one and two months was assessed according the International Bone Metastases Consensus criteria. INCLUSION CRITERIA: radiological evidence of BM, NP according to DN4 (cut-off score ≥ 4), no spinal cord compression, worst pain score ≥ 5/10. Nonparametric Mann-Whitney U test compared changes in QoL among response groups. RESULTS: Seventeen patients (13 men, 4 woman), median age 67 years (42-81), were included. Pre-treatment median pain severity was 7.5 (5-10). Median dose of tapentadol administered before radiotherapy was 100 mg/24 h (100-300 mg). Overall RR 1 month after radiotherapy was 10/16 = 62.5%: 3/16 (18.8%) achieving a complete response (CR) and 7/16 (43.8%) a partial response (PR). Overall RR 2 months after RT was 5/10 (50%): 10% a CR and 40% a PR. ITT RR for this study at 1 and 2 months was 10/17 = 59% and 5/17 = 29%, respectively. Patients responding to radiotherapy had significant improvement in EORTC QLQ-C30 emotional functioning (EF) (p = 0.025) and fatigue symptom scale scores (p = 0.035) one month after radiotherapy. Painful site symptom QLQ-BM22 scores improved 2 months after radiotherapy (p = 0.024). CONCLUSIONS: Palliative radiotherapy plus tapentadol shows an acceptable pain response and QoL improvement especially regarding EF, fatigue and painful site symptom scales in patients with moderate/severe NP due to BM. Therefore, it could be an alternative to manage NP in daily practice.

Pattern of relapse and dosimetric analysis of a single dose 19 Gy HDR-brachytherapy phase II trial.

PURPOSE: To report the pattern of relapse within the prostate with reference to the initial site of disease in patients treated with single fraction 19-Gy. METHODS AND MATERIALS: Forty-four patients were treated according to a prospective study of single-fraction HDR-brachytherapy. Treatment was delivered using 192Ir to a dose of 19 Gy prescribed to the prostate. Patients who experienced a biochemical failure underwent a re-staging multiparametric MRI (mpMRI) and MRI-TRUS fusion biopsy to rule-out local recurrence. In patients with visible Dominant intraprostatic lesions (DIL) on pretreatment mpMRI, the site of local relapse was compared with the initial site of disease. The dose received by the site of recurrence was investigated. RESULTS: The median follow-up period was 48 months (range 29-63). The PSA nadir was reached at 24 months follow-up, with a median value of 1.07 ng/mL. To date, 14 patients (32%) have experienced biochemical failure (4 patients low-risk and 10 intermediate-risk; p = 0.013). Re-staging mpMRI was performed in 11/14 patients. Eleven patients underwent MRI-TRUS fusion biopsy confirming local relapse in all patients. The analysis of DVH of all 44 patients revealed that patients with biochemical failure had received significantly lower doses in terms of V100, V125 and D90 (p = 0.032, p = 0.018 and p = 0.018 respectively). In patients with DILs on diagnostic mpMRI, the mean D90 and D98 on DIL were lower for patients with biochemical failure. CONCLUSIONS: This dosimetric analysis demonstrates a dose-response relationship in patients treated with single fraction 19 Gy. Patients with intermediate risk disease, with visible DIL on mpMRI and patients treated with cooler implants have higher incidence of biochemical and local failure.

Late toxicity after single dose HDR prostate brachytherapy and EBRT for localized prostate cancer: Clinical and dosimetric predictors in a prospective cohort study.

PURPOSE: To describe the genitourinary (GU) and gastrointestinal (GI) late toxicity profile and to analyse the clinical and dosimetry outcomes predictors of the combination of EBRT and high-dose-rate (HDR) prostate brachytherapy (BT) for localized prostate cancer. MATERIALS AND METHODS: Between January 2012 and May 2017, 210 patients were included in a prospective protocol. Treatment consisted in HDR-BT (15 Gy single fraction) plus 3DCRT (37.5 Gy/15 fractions). Univariate and multivariate logistic regressions were used to analyse the impact of variables on late toxicity. RESULTS: Median age was 71 (56-82), 12.4% of patients had low, 44.3% intermediate and 41% high-risk prostate cancer. Median prostate volume was 28.4 cc. Median V100, V150, V200 were 98.2%, 27% and 7.4% respectively. Median urethra Dmax, rectum D1cc and D2cc, were 113.5%, 62.2%% and 54.2% respectively. After a median follow-up of 41 months (5-75) late G2 GU and GI late toxicity was observed in 14.8% and 5.2% of patients respectively. Late G3 GU and GI toxicity occurred in 0% and 1% of patients respectively. There were no outcome correlations with late G ≥ 2 GU toxicity on univariate analysis. Previous cardiovascular comorbidity (p = 0.042), and dose to the rectum D2cc (p = 0.016) and D1cc (p = 0.017) were associated with G ≥ 2 GI toxicity. Multivariate analysis showed that rectum D1cc (HR11.56; 95%CI 1.4-92.1; p = 0.021) and prior history of cardiovascular disease (HR3.6; 95%CI 1-12.9; p = 0.045) remained independent predictors of G ≥ 2 GI toxicity. CONCLUSIONS: There is a low incidence of late GU and GI morbidity using single fraction HDR-BT and hypofractionated EBRT. Previous cardiovascular disease and dose to the rectum were observed to correlate with GI toxicity.

Long-term Outcomes and Patterns of Failure Following Trimodality Treatment With Bladder Preservation for Invasive Bladder Cancer.

OBJECTIVE: To report long-term results on survival, toxicity, and patterns of failure of 3 different organ-sparing strategies for patients with muscle invasive bladder cancer. MATERIALS AND METHODS: This is a monoinstitutional prospective analysis of 3 consecutive bladder-sparing protocols combining maximal transurethral resection of bladder tumor (mTURBT), radiotherapy (RT), and cisplatin-based chemotherapy. Protocol 1 consisted of neoadjuvant methotrexate-cisplatin-vinblastine followed by endoscopic re-evaluation and consolidative RT 60 Gy in complete responders. Protocol 2 involved altered-fractionation RT 64.8 Gy and concurrent weekly cisplatin with re-evaluation after 40.8 Gy. Protocol 3 consisted of RT 64.8 Gy with concomitant weekly cisplatin. Nonresponders underwent radical cystectomy. Probabilities for overall survival (OS), cancer-specific survival (CSS), and metastasis-free survival (MFS) were calculated using Kaplan-Meier product limited estimates. A Cox regression multivariate analysis was performed to detect potential risk factors for OS, CSS, and MFS. RESULTS: The 10-year bladder preservation rate was 79%. The 10-year OS, CSS, and MFS rates were 43.2%, 76.3% and 79.2%, respectively. There was no statistically significant difference in OS between the different treatment protocols. On multivariate analysis, mTURBT of the bladder and the complete response after induction therapy were independent correlates of improved OS and of MFS. The development of invasive bladder recurrence was independently associated with worse CSS and MFS. CONCLUSION: Ten-year results indicate that bladder-sparing treatment is a successful approach for muscle invasive bladder cancer in selected patients. The mTURBT of the bladder tumor and complete response after induction therapy remain the most relevant predictive factors.

Pretreatment Multiparametric Magnetic Resonance Imaging Findings Are More Accurate Independent Predictors of Outcome Than Clinical Variables in Localized Prostate Cancer.

PURPOSE: To prospectively determine whether multiparametric magnetic resonance imaging (mpMRI)-based staging is a more accurate independent predictor of outcome than traditional clinical variables for patients undergoing brachytherapy and external beam radiation therapy. METHODS AND MATERIALS: The primary endpoints were biochemical (nadir plus 2 ng/mL) and metastatic failure. Descriptive, univariate, and multivariate competing risks analyses were performed. The cumulative incidence rates were estimated to describe the cumulative risk of the events of interest. The magnitude of the increased risk was estimated using univariate and multivariate subdistribution hazard ratios. RESULTS: A total of 185 patients had undergone prospective treatment (123 with high risk and 62 with intermediate risk). The median age was 71 years (range 56-82). Of the patients, 20.5% had mpMRI-determined (mrT) stage mrT1-mrT2b, 37.3% had mrT2c, 31% had mrT3a, and 11.2% had mrT3b. The Gleason score was 6 in 22.2%, 7 in 49.5%, and 8 to 10 in 28.2%. The median baseline prostate-specific antigen was 11.7 ng/mL (range 2.9-153). After a median follow-up period of 46 months (range 16-70), 15 patients (8.1%) had developed biochemical failure and 9 (4.9%) had developed distant metastases. None of the traditional clinical variables (prostate-specific antigen, Gleason score, clinical stage) predicted for biochemical or metastatic failure. The multivariate competing risk analysis demonstrated that the 2 independent predictors of biochemical failure were the presence of extraprostatic extension (EPE; mrT3a; hazard ratio [HR] 4.80; P = .035) and presence of seminal vesicle invasion (SVI; mrT3b; HR 10.17; P = .003) on mpMRI. The only independent predictor of metastatic failure was the percentage of positive cores on prostate biopsy (HR 13.95; P = .014). After excluding patients with SVI, the only independent predictor of biochemical failure and metastatic failure was the presence of EPE (stage mrT3a) on mpMRI (HR 4.36; P = .042; and HR 5.76; P = .010, respectively). CONCLUSIONS: The pretreatment mpMRI findings might be more accurate independent predictors of the outcome than traditional clinical variables. In particular, the presence of EPE, SVI and a greater percentage of positive cores on biopsy predicted for a worse prognosis.

Health-related-quality-of-life and toxicity after single fraction 19 Gy high-dose-rate prostate brachytherapy: Phase II trial.

PURPOSE: To evaluate the safety, tolerance and impact on health-related-quality-of-life (HRQoL) of the high-dose-rate brachytherapy of 19 Gy (BRT-HDR-19 Gy) single fraction in prostate cancer. METHODS: From January 2014 to July 2016, 43 patients with low/intermediate risk were treated with BRT-HDR-19 Gy. The patients were monitored prospectively for toxicity and HRQoL. RESULTS: The median age, initial PSA and the International Prostate Symptom Score (IPSS) were 71 years (55-78), 7.0 ng/mL (4.2-17.8) and 5 (0-14) respectively. 44% were low-risk and 56% intermediate-risk. Median CTV-V100 (where Vn is the fractional volume of the organ that receives n% of the prescribed dose) was 96.5%, Urethral-Dmax 106% and rectum-2 cc (the dose to 2 cc of rectal wall) 53%. After a median follow-up of 20 months (4-26), acute grade-2 genitourinary (GU) toxicity occurred in 4 patients (9%) and none presented acute gastrointestinal (GI) toxicity. Similarly, four patients (9%) presented late GU grade-2 toxicity. No grade-3 toxicity occurred. In terms of HRQoL, there was a statistically significant decline in Expanded Prostate Cancer Index Composite (EPIC) urinary urgency/obstructive domain at month 3 (p = 0.047), and returned to baseline by month 6. Mean EPIC urinary incontinence, bowel, sexual and hormonal domains did not present significant post BRT-HDR-19 Gy changes. Patients rated their satisfaction at 6 months as "very-satisfied" (23%) or "extremely-satisfied" (77%). CONCLUSIONS: BRT-HDR-19 Gy demonstrates excellent results in terms of toxicity, tolerance, safety, patient satisfaction and HRQoL.

Products based on olive oil, betaine, and xylitol in the post-radiotherapy xerostomia.

AIM: The objective of this study was determining if the use of products based in olive oil, betaine and xylitol are efficacious to decrease the impact of the dry mouth in the quality of life of the patients with xerostomia due to radiotherapy treatment. BACKGROUND: Following therapeutic irradiation of the head and neck, patients with profound xerostomia have complaints associated with oral dryness, speech, and taste. There is no strong evidence that any topical therapy is effective for relieving the symptom of dry mouth. MATERIAL AND METHODS: 40 patients who had been treated with radiotherapy for head and neck carcinoma and reported symptoms of dry mouth were included in the study. A xerostomia-related quality of life questionnaire, visual analogue scale questionnaire for subjective assessment of salivary dysfunction and salivary flow were reported before and 15 days after the use of topical products based on olive oil, betaina and xylitol. RESULTS: The four primary quality of life areas demonstrated significantly greater improvement after the use of topical products and all eight VAS items had favourable changes. The reduction of symptoms was statistically significant in 7 of the 8 items. After the use of the products, there were improvements in salivary flow in 45%. CONCLUSIONS: The use of products based on olive oil, betaine and xylitol, shaped like collutory, toothpaste, gel and spray significantly improved most symptoms and the quality of life limitations produced by dry mouth in patients treated with radiotherapy.

Salvage high-dose-rate brachytherapy for histologically confirmed macroscopic local relapsed prostate cancer after radical prostatectomy.

PURPOSE: To evaluate the feasibility of the use of real-time magnetic resonance imaging (MRI)-transrectal ultrasound (TRUS) fusion guided high-dose-rate brachytherapy (HDR-BT) +/- external beam radiation therapy (EBRT) in patients with histologically-proven local relapse after radical prostatectomy. MATERIAL AND METHODS: We retrospectively reviewed 13 patients treated with real-time MRI-TRUS fusion HDR-BT for a local relapse of prostate cancer after radical surgery. All patients underwent multiparametric magnetic resonance imaging (mpMRI) to confirm the presence of macroscopic lesions in prostate bed, and choline positron emission tomography/computed tomography (PET/CT) to rule out nodal or distant metastases. Local failure was confirmed by transrectal biopsy. Patients without previous EBRT received 1 fraction of 15 Gy with HDR-BT plus hypofractionated EBRT (37.5 Gy in 15 fractions). Two patients received 2 fractions of 12 Gy with HDR-BT without EBRT. Follow-up visits were at 1, 3, 6 months, and every 6 months thereafter. RESULTS: After a median follow-up of 7 months, all patients showed an appropriate biochemical response. Median prostate-specific antigen (PSA) levels before treatment, 1 month, and 6 months after HDR-BT were 2.62 ng/ml (range: 1.55-9.61), 0.97 ng/ml (range: 0.12-3.14), 0.23 ng/ml (range: 0.1-0.74), respectively. Five patients (42%) experienced acute grade 1 GU toxicity and 1 patient (8%) suffered from grade 2 GU toxicity. Regarding gastrointestinal (GI) toxicity, 5 patients referred grade 1 acute toxicity and 1 grade 2 (proctitis). No late toxicity has been observed so far. CONCLUSIONS: MRI-TRUS fusion guided salvage HDR-BT +/- EBRT is a feasible procedure for patients with local macroscopic relapse in tumor bed after radical prostatectomy. Exquisite selection of patients through mpMRI and choline PET/CT is crucial to avoid overtreatment. A larger number of patients and longer follow-up are required in order to draw more solid conclusions regarding the effectiveness of this strategy.

Bystander effects and radiotherapy.

Radiation-induced bystander effects are defined as biological effects expressed after irradiation by cells whose nuclei have not been directly irradiated. These effects include DNA damage, chromosomal instability, mutation, and apoptosis. There is considerable evidence that ionizing radiation affects cells located near the site of irradiation, which respond individually and collectively as part of a large interconnected web. These bystander signals can alter the dynamic equilibrium between proliferation, apoptosis, quiescence or differentiation. The aim of this review is to examine the most important biological effects of this phenomenon with regard to areas of major interest in radiotherapy. Such aspects include radiation-induced bystander effects during the cell cycle under hypoxic conditions when administering fractionated modalities or combined radio-chemotherapy. Other relevant aspects include individual variation and genetics in toxicity of bystander factors and normal tissue collateral damage. In advanced radiotherapy techniques, such as intensity-modulated radiation therapy (IMRT), the high degree of dose conformity to the target volume reduces the dose and, therefore, the risk of complications, to normal tissues. However, significant doses can accumulate out-of-field due to photon scattering and this may impact cellular response in these regions. Protons may offer a solution to reduce out-of-field doses. The bystander effect has numerous associated phenomena, including adaptive response, genomic instability, and abscopal effects. Also, the bystander effect can influence radiation protection and oxidative stress. It is essential that we understand the mechanisms underlying the bystander effect in order to more accurately assess radiation risk and to evaluate protocols for cancer radiotherapy.

Dermatofibrosarcoma Protu-Berans with Lung Metastasis Requiring Pneumonectomy.

We report the case of a young man diagnosed with dermatofibrosarcoma protuberans lung metastases seven years after primary tumor resection. Notably, no previous local recurrences had been observed. A multimodal approach was used for the management of this patient: surgery, radiotherapy and targeted therapy with Imatinib. The patient is alive with stable disease after thirty months of the metastases diagnoses. Dermatofibrosarcoma protu-berans metastasizes very rarely, and when it does, it is usually either after local recurrence or whenever fibrosarcomatous transformation is found in the histopathological analysis, which confers an increased risk of local recurrence and metastases. This is the second report of a metastatic dermatofibrosarcoma protuberans occurring in a patient with no previous local recurrence or histological fibrosar-comatous features, emphasizing the rarity of the disease presentation and the importance of targeted therapy in improving patient quality of life and survival.