The MUSES∗: a prognostic study on 1360 patients with sinonasal cancer undergoing endoscopic surgery-based treatment: ∗MUlti-institutional collaborative Study on Endoscopically treated Sinonasal cancers.

BACKGROUND: Over the last 2 decades, transnasal endoscopic surgery (TES) has become the most frequently employed surgical technique to treat sinonasal malignancies. The rarity and heterogeneity of sinonasal cancers have hampered large non-population-based analyses. METHODOLOGY: All patients receiving TES-including treatment between 1995 and 2021 in 5 referral hospitals were included. A prognostic study was performed, and multivariable models were transformed into nomograms. Training and validation sets were based on results from 3 European and 2 non-European centres, respectively. RESULTS: The training and validation set included 940 and 420 patients, respectively. The mean age at surgery, primary-versus-recurrent presentation, histology distribution, type of surgery, T category and type of adjuvant treatment were differently distributed in the training and validation set. In the training set, 5-year overall survival and recurrence-free survival with a 95%-confidence interval were 72.7% (69.5-76.0%) and 66.4% (63.1-69.8%), respectively, significantly varying with histology. At multivariable analyses, age, gender, previous treatment, the extent of resection on the cranial, lateral and posterolateral axes, grade/subtype, T category, nodal status, margin status and adjuvant treatment were all associated with different prognostic outcomes, displaying a heterogeneous significance and effect size according to histology. The internal and external validation of nomograms was satisfactory (optimism-corrected C-index >0.7 and cumulative area under curve >0.7) for all histologies but mucosal melanoma. CONCLUSIONS: Outcomes of TES-based treatment of sinonasal cancers vary substantially with histology. This large, non-population-based study provides benchmark data on the prognosis of sinonasal cancers that are deemed suitable for treatment including TES.

Universal testing for COVID-19 in patients undergoing cancer treatment during the second outbreak in Brescia.

BACKGROUND: The impact of coronavirus disease 2019 (COVID-19) has been overwhelming on patients with cancer, who may be at higher risk of developing severe disease. During the second COVID-19 outbreak in Italy, we planned universal microbiologic screening for patients scheduled for antineoplastic treatment. METHODS: All patients with planned active treatment at Brescia University Radiation Oncology Department were screened for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA with repeated nasopharyngeal swabs (NPS) from October 31, 2020. Treatment continuation, suspension, or delay was modulated for patients testing positive according to clinical presentation. RESULTS: From October 31, 2020, to February 6, 2021, 636 patients were enrolled and 1243 NPS were performed, of which 28 (2.25%) were positive. The infection rate was 2.52%; 81.3% of the patients with a positive NPS were asymptomatic, 2 had mild disease, and 1 severe disease that led to death. All patients already on treatment with mild or asymptomatic COVID-19 carried on the therapy with no or minimal delay. Median delay for patients with infection detected before treatment start was 16.5 days. CONCLUSIONS: Detected incidence of COVID-19 was lower during the second outbreak in our patients (2.52% vs 3.23%), despite the extensive testing schedule, and substantiates the high rate of asymptomatic infections and the low mortality among patients with COVID-19 (6.3% vs 38.5% during the first outbreak). Universal SARS-CoV-2 screening for all patients with planned treatment might allow early identification of patients with COVID-19, resulting in timely management that could improve clinical outcomes and prevent spread of the infection.

Health-related quality of life 24 months after prostate cancer diagnosis: an update from the Pros-IT CNR prospective observational study.

BACKGROUND: This study analyzes patient health-related quality of life (QoL) 24-month after prostate cancer (PCa) diagnosis within the PROState cancer monitoring in ITaly from the National Research Council (Pros-IT CNR) study. METHODS: Pros-IT CNR is an ongoing, longitudinal and observational study, considering a convenience sample of patients enrolled at PCa diagnosis and followed at 6, 12, 24, 36, 48 and 60 months from the diagnosis. Patients were grouped according to the treatment received: nerve sparing radical prostatectomy (NSRP), non-nerve sparing radical prostatectomy (NNSRP), radiotherapy (RT), RT plus androgen deprivation (RT plus ADT) and active surveillance (AS). QoL was measured through the Italian versions of SF-12 and UCLA-PCI questionnaires at diagnosis and at 6-12 and 24-month. The minimal clinically important difference (MCID) was defined as half a standard deviation of the baseline domain. RESULTS: Overall, 1537 patients were included in the study. The decline in urinary function exceeded the MCID at each timepoint only in the NSRP and NNSRP groups (at 24 months -14.7, P<0.001 and -19.7, P<0.001, respectively). The decline in bowel function exceeded the MCID only in the RT (-9.1, P=0.02) and RT plus ADT groups at 12 months (-10.3, P=0.001); after 24 months, most patients seem to recover their bowel complaints. The decline in sexual function exceeded the MCID at each timepoint in the NNSRP, NSRP and RT plus ADT groups (at 6 months -28.7, P<0.001, -37.8, P<0.001, -20.4, P<0.001, respectively). CONCLUSIONS: Although all the treatments were relatively well-tolerated over the 24 month period following PCa diagnosis, each had a different impact on QoL.

The waiting time for prostate cancer treatment in Italy: analysis from the PROS-IT CNR Study.

BACKGROUND: Prostate cancer (PCa) is the second most common neoplasm in male patients. To date, there's no certain indication about the maximum waiting time (WT) acceptable for treatment beginning and the impact on oncological and functional outcomes has not been well established. METHODS: Data from the National Research Council PCa monitoring multicenter project in Italy (Pros-IT CNR) were prospectively collected and analyzed. WT was defined as the time from the bioptical diagnosis of PCa to the first treatment received. Patients were divided in two groups, using a time frame of 90 days. Quality of life was measured through the Italian version of the University of California Los Angeles-Prostate Cancer Index (UCLA-PCI) and of the Short-Form Health Survey (SF-12). The occurrence of upgrading, upstaging, presence of lymph node metastasis and positive surgical margins at the final histopathological diagnosis, and PSA at 12 months follow-up were evaluated. RESULTS: The overall median WT was 93 days. The logistic multivariable model confirmed that age, being resident in Southern regions of Italy and T staging at diagnosis were significantly associated with a WT>90 days. At 6 months from diagnosis the mean SF-12 score for the emotional-psychological component was significantly lower in WT≥90 days group (P=0.0428). Among patients treated with surgical approach, no significant differences in oncological outcomes were found in the two groups. CONCLUSIONS: In our study age, clinical T stage and provenance from Southern regions of Italy are associated with a WT>90 days. WT might have no impact on functional and oncological outcome.

The Italian Association of Radiotherapy and Oncology Recommendation for Breast Tumor Recurrence: Grades of Recommendation, Assessment, Development and Evaluation Criteria.

Salvage mastectomy is currently considered the standard of care for ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery (BCS) and postoperative radiotherapy (RT). Alternative treatment options for these patients, such as a second BCS followed by repeated RT, have been suggested. The panel of the Italian Association of Radiotherapy and Clinical Oncology developed clinical recommendations for second BCS followed by re-irradiation over mastectomy alone for women with IBTR using the Grades of Recommendation, Assessment, Development, and Evaluation methodology and the evidence to decision framework. The following outcomes were identified by the panel: locoregional control, metastasis-free survival, overall survival, and cancer-specific survival; acute and late toxicity, specific late toxicity, second locoregional tumor, and death related to treatment. An Embase and PubMed literature search was performed by two independent authors. Five retrospective observational studies were eligible for inclusion in the present analysis. According to the reports in the literature and our analysis, the advantages of second quadrantectomy and re-irradiation (re-QUART) outweigh its side effects, with overall good rates of survival and adequate toxicity without increasing costs. Given the very low level of evidence, the panel stated that a second BCS plus re-irradiation can be considered as an alternative to salvage mastectomy for selected patients with IBTR.

Survival and toxicity of weekly cisplatin chemoradiotherapy versus three-weekly cisplatin chemoradiotherapy for head and neck cancer: A systematic review and meta-analysis endorsed by the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

PURPOSE: To evaluate efficacy and toxicity of weekly cisplatin chemoradiotherapy versus three-weekly cisplatin chemoradiotherapy and identify differences in clinical outcomes and severe toxicity rate. METHODS: PICOS/PRISMA methods were used to identify studies on PubMed, EMBASE and Cochrane Library, 2005-2019. RESULTS: Six randomized clinical trials (554 patients) were identified. Weekly cisplatin was not associated with significant overall survival (HR 1.13, 95 % CI 0.84-1.51) and progression-free survival (HR 1.23, 95 %CI 0.91-1.65) improvement compared with three-weekly regimen. Severe acute toxicity (RR 0.95), treatment compliance to chemotherapy (RR 1.67) and radiotherapy (RR 0.61) were similar between regimens. CONCLUSION: Weekly cisplatin is not associated with better clinical outcomes compared to three-weekly cisplatin. Three-weekly cisplatin chemoradiotherapy should be considered the standard approach in the management of locally advanced head and neck cancer. Methodologically robust RCTs designs are needed to improve the quality of evidence. Differences on long-term toxicity and cost-effectiveness remain to be tested.

Adjuvant radiotherapy and radioiodine treatment for locally advanced differentiated thyroid cancer: systematic review and meta-analysis.

BACKGROUND: Treatment for locally advanced differentiated thyroid cancer is surgery followed by radioiodine while the role of adjuvant external beam radiotherapy (EBRT) is debated. METHODS: The panel of the Italian Association of Radiotherapy and Clinical Oncology developed a clinical recommendation on the addition of EBRT to radioiodine after surgery for locally advanced differentiated thyroid cancer by using the Grades of Recommendation, Assessment, Development, and Evaluation methodology and the Evidence to Decision framework. A systematic review with meta-analysis about this topic was conducted with a focus on outcome of benefits and toxicity. RESULTS: Locoregional control was improved by EBRT while no considerable toxicity impact was reported. CONCLUSION: The panel judged uncertain the benefit/harms balance; final recommendation was conditional both for EBRT + radioiodine and radioiodine alone in the adjuvant setting.

Loco-regional adjuvant radiation therapy in breast cancer patients with positive axillary lymph-nodes at diagnosis (CN2) undergoing preoperative chemotherapy and with complete pathological lymph-nodes response. Development of GRADE (Grades of recommendation, assessment, Development and Evaluation) recommendation by the Italian Association of radiation therapy and Clinical Oncology (AIRO).

OBJECTIVE: To perform a meta-analysis to determine the effect of loco-regional radiation therapy (RT) compared to no loco-regional RT for operated patients in clinical stage cN2 breast cancer at diagnosis and ypN0 after preoperative chemotherapy (PST). MATERIAL AND METHODS: Eligible studies were identified through a systematic search of the medical literature performed independently by two researchers using a validated search strategy. An electronic search of Medline via PubMed and Embase (Breast cancer AND preoperative chemotherapy AND radiation therapy) was conducted with no language or publication status restrictions. The effect of loco-regional RT on overall (OS), disease free (DFS), loco-regional recurrence-free (LRRFS) survival and local recurrence was evaluated. An electronic search of Medline via PubMed and Embase (Toxicity AND radiation therapy breast cancer AND preoperative therapy; toxicity AND breast surgery AND preoperative chemotherapy) was conducted for outcomes of harm: major acute and late skin toxicity, lymphedema and cardiac events. RESULTS: Of 333 studies identified, 4 retrospective studies reporting on a total of 1107 patients were included in the meta-analysis. Six and 3 reported data of acute and late skin toxicity, while 2 studies provided information on cardiac events. Pooled results showed no difference in terms of hazard ratio for loco-regional RT versus no loco-regional RT [hazard ratio (HR) = 0.82, 95% confidence interval (CI) 0.63-1.68]. Loco-regional RT was associated with an OS benefit in the subgroup analysis: IIIB-C (loco-regional RT 79.3% vs no loco-regional RT 71.2%, p = 0.027) and T3-T4 (loco-regional RT 82.6% vs no loco-regional RT 76.6%, p = 0.025). No difference was shown in terms of 5-year DFS (loco-regional RT 91.2% vs no loco-regional RT 83%, p = 0.441) and LRRFS (loco-regional RT 98.1% vs no loco-regional RT 92.3%, p = 0.148). There was no significant difference between the groups in terms of acute and late skin toxicities, lymphedema and cardiac events. CONCLUSIONS: Because of the limitations due to the small number of studies and heterogeneity in the analysis, the present study does not allow to draw any definitive conclusion, highlighting the need for well-controlled trials to determine the effect of loco-regional RT in patients with cN2 having a pathological complete response in the axillary nodes after preoperative chemotherapy.

Post-operative management of brain metastases: GRADE-based clinical practice recommendations on behalf of the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

PURPOSE: To perform a systematic review of the current level of evidence on post-operative management following brain metastasectomy (namely: adjuvant stereotactic radiosurgery, whole brain radiotherapy or observation), and to propose a GRADE-based dedicated recommendation to inform Radiation Oncologists' clinical practice. METHODS: A panel of expert Radiation Oncologists from the Italian Association of Radiotherapy and Clinical Oncology had defined the search question per the PICO methodology. Electronic databases were independently screened; the Preferred Reporting Items for Systematic Reviews and Meta-Analyses was adopted. The individual and pooled hazard ratios with 95% confidence intervals (CI), as well as the pooled risk ratio (RR) were calculated using a fixed- or random-effects model. RESULTS: Eight full-texts were retrieved: six retrospective studies and two randomized clinical trials. Outcomes of benefit and damage were analyzed for SRS + observation (PICO A) and SRS + WBRT. SRS allowed for increased rates of local control when compared to both observation and WBRT, while evidence was less conclusive for distant brain control, leptomeningeal disease control and overall survival. In the SRS, the incidence of severe radionecrosis was higher as compared to WBRT, despite neurocognitive deterioration rates were lower. Overall, SRS seems to favorably compare with observation and whole brain RT, despite the level of evidence for the recommendation was low and very low, respectively. CONCLUSION: Despite low level of evidence, the panel concluded that the risk/benefit ratio probably favors adjuvant SRS as compared to the observation and whole brain RT as adjuvant treatments following brain metastasectomy (5 votes/5 participants, 100% attendance).

Overview of potential determinants of radical prostatectomy versus radiation therapy in management of clinically localized prostate cancer: results from an Italian, prospective, observational study (the Pros-IT CNR study).

BACKGROUND: We assessed patients and tumor characteristics, as well as health-related quality of life (HRQoL) items, associated with curative intent treatment decision-making in clinically localized prostate cancer (PCa) patients. METHODS: Clinically localized PCa treated with either radical prostatectomy (RP) or radiation therapy (RT) within 12 months from diagnosis were abstracted from The PROState cancer monitoring in ITaly, from the National Research Council (Pros-IT CNR) database. Multivariable logistic regression (MLR) models predicting RT vs. RP were fitted, after adjustment for HRQoL items, patients and tumor characteristics. RESULTS: Of 1041 patients, 631 (60.2%) were treated with RP and 410 (39.8%) with RT. Relative to RT, RP patients were younger age (mean age 64.5±6.6 vs. 71.4±4.9, P<0.001) and had higher rates of D'Amico low-intermediate risk groups (31.8 vs. 21.9% low, 46.3% vs. 43.5% intermediate and 21.9% vs. 34.6% high risk, P<0.001). Overall, 93.2% of RP patients were enrolled by urologists and 82.7% of RT patients by radiation oncologists. RP patients had generally higher means values of HRQoL items. In MLR models, higher RT rates were independently associated with more advanced age (odds ratio [OR] 6.14, P<0.001) and BMI≥30 kg/m2 (OR 1.78, P<0.001). Conversely, lower rates of RT were independently associated with married (OR 0.55, P=0.01) and worker status (OR 0.52, P=0.004), enrollment in academic centers (OR 0.59, P=0.005) and higher physical composite score (OR 0.88, P=0.03) and baseline sexual function items (OR 0.92, P<0.001). CONCLUSIONS: Most patients with clinically localized prostate cancer undergoing definitive treatment at Italian institutions receive RP instead of RT. Moreover, those who are younger, married, working, as well as those with better physical and sexual function are more likely to undergo surgery.

A pilot study on the Vanderbilt head and neck symptom survey Italian version (VHNSS-IT) to test its feasibility and utility in routine clinical practice.

PURPOSE: Patient-reported outcome measures can be useful to assess symptoms in head and neck cancer (HNC) patients treated with radio-chemotherapy. This is a pilot study on the VHNSS-IT (the Italian version of the Vanderbilt head and neck symptom survey) performed to assess both the feasibility and utility of its administration in clinical practice. METHODS: The outcomes analyzed were feasibility to recruit patients, feasibility to complete the questionnaire, feasibility to review the questionnaire, utility perceived by clinicians, distribution of patient's answers reflecting symptom's intensity. RESULTS: Among the 38 patients enrolled, 37 completed the VHNSS-IT (refusal rate 2.6%). Median time of completion was 6'57″. Time of completion was influenced by age (p = 0.002), grade of education (p = 0.023) and employment status (p = 0.004). Time after the start of the radiotherapy course (< 6 months vs. > 6 months) and surgery (yes vs. no) influenced symptoms' intensity. Median time for review was 2'15″. Time burden was perceived to be acceptable for all clinicians; they all also found the questionnaire easy to use. Rates of global perceived utility and future intention to use the questionnaire were 100%. CONCLUSIONS: The VHNSS-IT has demonstrated to be a useful measurement of symptoms' burden for patients with HNC. The survey can be easily completed during the clinic routine without interfering with doctors' visits schedule, and it can help healthcare providers to identify symptoms that require referral, education or intervention.

The linguistic validation process of the Vanderbilt Head and Neck Symptom Survey - Italian Version (VHNSS-IT).

PURPOSE: To linguistically validate the Italian translation of the Vanderbilt Head and Neck Symptom Survey (VHNSS), there is a patient-reported outcome measure to screen for symptoms in the head and neck cancer (HNC) patients population. The goal was to ensure conceptually equivalence with the original version and maintain clarity, ease of use and understanding. METHODS: We conducted a multi-step linguistic process (forward translation, backward translation and patient testing) to generate and validate an Italian translation of the VHNSS. RESULTS: Two intermediate Italian versions were created: The first Italian version was derived from a reconciliation of the three forward translations, and the second Italian version was derived from changes in the first version after the backward translation step. All investigators involved actively discussed possible solutions to produce a translated instrument that maintained a reading and comprehension level accessible by most respondents, without altering the meaning and content of the original source. During the patient testing step, only two patients reported problems with items comprehension and the rate of comprehension problems per single item was lower than expected. This phase allowed patients to give suggestion in order to make items clearer and easier to understand: 43% of patients proposed a revision of the survey during the face-to-face interview, and most of these suggestions were retained. CONCLUSIONS: A valid multi-step process leads to the creation of the final version of the VHNSS-IT, a suitable instrument to screen for symptoms in the Italian HNC patients population and an official measurement tool that can be used in cooperative research group.

Hypofractionated radiation therapy versus chemotherapy with temozolomide in patients affected by RPA class V and VI glioblastoma: a randomized phase II trial.

INTRODUCTION: In RPA V-VI glioblastoma patients both hypofractionated radiotherapy and exclusive temozolomide can be used; the purpose of this trial is to compare these treatment regimens in terms of survival and quality of life. METHODS: Patients with histologic diagnosis of glioblastoma were randomized to hypofractionated radiotherapy (RT-30 Gy in 6 fractions) and exclusive chemotherapy (CHT-emozolomide 200 mg/m2/day 5 days every 28 days). Overall (OS) and progression free survival (PFS) were evaluated with Kaplan Maier curves and correlated with prognostic factors. Quality- adjusted survival (QaS) was evaluated according to the Murray model (Neurological Sign and Symptoms-NSS) RESULTS: From 2010 to 2015, 31 pts were enrolled (CHT: 17 pts; RT: 14pts). Four pts were excluded from the analysis. RPA VI (p = 0.048) and absence of MGMT methylation (p = 0.001) worsened OS significantly. Biopsy (p = 0.048), RPA class VI (p = 0.04) and chemotherapy (p = 0.007) worsened PFS. In the two arms the initial NSS scores were overlapping (CHT: 12.23 and RT: 12.30) and progressively decreased in both group and became significantly worse after 5 months in CHT arm (p = 0.05). Median QaS was 104 days and was significantly better in RT arm (p = 0.01). CONCLUSIONS: The data obtained are limited by the poor accrual. Both treatments were well tolerated. Patients in RT arm have a better PFS and QaS, without significant differences in OS. The deterioration of the NSS score would seem an important parameter and coincide with disease progression rather than with the toxicity of the treatment.

Consensus statements on ablative radiotherapy for oligometastatic prostate cancer: A position paper of Italian Association of Radiotherapy and Clinical Oncology (AIRO).

Oligometastatic prostate cancer comprises a wide spectrum of conditions, ranging from de novo oligometastatic cancer at diagnosis to oligometastatic castration-resistant disease, which are distinct entities in terms of biology and prognosis. In order to clarify and standardize the clinical role of ablative radiotherapy in oligometastatic prostate cancer, the Italian Association of Radiotherapy and Clinical Oncology (AIRO) formed an expert panel to review the current literature and develop a formal consensus. Oligometastatic prostate cancer was defined as the presence of up to three metastatic lesions involving bones or nodes outside pelvis. Thereafter, four clinical scenarios were explored: metastatic castration-sensitive disease at diagnosis and after primary treatment, and metastatic castration-resistant disease at diagnosis and during treatment, where the role of ablative radiotherapy was defined either in conjunction with systemic therapy or as the only treatment in selected cases. This paper summarizes the current literature about these issues and the proposed recommendations.

Bone metastases from head and neck malignancies: Prognostic factors and skeletal-related events.

BACKGROUND: We conducted a multicenter retrospective analysis to describe the characteristics, frequency of skeletal-related events (SREs), and prognosis of head and neck cancer (HNC) in patients with bone metastases (BM). PATIENTS AND METHODS: The data of 192 HNC patients with BMs were collected. Analyses were conducted separately in 64 nasopharyngeal cancer (NPC) patients and in 128 non-NPC patients. RESULTS: SREs occurred in 34 (27%) non-NPC and in 6 (9%) NPC patients, respectively. Median overall survival (OS) was 25 and 6 months in NPC and non-NPC patients, respectively. Locoregional recurrence (hazard ratio [HR] 2.33, 95% confidence interval (CI) 1.1-4.93), synchronous BM (HR 0.25, 95% CI 0.59-0.71) and bone-directed therapies (BDT) (HR 0.26, 95% CI 0.10-0.68) were independent prognostic factors for OS in NPC patients. Combined bone radiotherapy (RT) and BDT in NPC patients obtained longer survival (38 months) than either therapy alone (25 months) or neither of these therapies (8 months). CONCLUSIONS: Patients with BMs from non-NPC have a poor prognosis and are at high risk of SREs. NPC patients with BMs are at relatively low risk of SREs. BDT may potentially improve survival, particularly when combined with bone RT. This last finding deserves prospective confirmation.

Equipment, staffing, and provision of radiotherapy in Lombardy, Italy: Results of three surveys performed between 2012 and 2016.

INTRODUCTION:: Several efforts are being implemented at the European level to measure provision of up-to-date radiation treatments across the continent. METHODS:: A snapshot survey involving all radiation oncology centers within Lombardy, Italy, was performed in 2012 and repeated in 2014 and 2016, in cooperation with regional governmental officers. Centers were asked to provide detailed information concerning all individual patients being treated on the index day, and to report data on available local resources. RESULTS:: We observed an increase in the number of centers and of megavoltage units (MVU) (from 76 to 87, i.e., 8.7 MVU per million inhabitants in 2016). Mean number of MVU per center was 2.5. Average age of MVU increased from 5.3 to 7.5 years and patients on the waiting list also increased. Conformal 3D radiotherapy (RT) treatments decreased from 56% to 42% and were progressively replaced by intensity-modulated RT treatments (from 39% to 49%). Waiting times were overall satisfactory. Radiation oncologists treated on average 152 and radiation therapists 100 RT courses per year. Average reimbursement per course was €4,879 (range €2,476-€8,014). CONCLUSIONS:: The methodology of snapshot survey proved feasible and provided valuable information about radiation oncology provision and accessibility in Lombardy.

Extreme hypofractionation for early prostate cancer: Biology meets technology.

The aim of this review is to present the available radiobiological, technical and clinical data about extreme hypofractionation in primary prostate cancer radiotherapy. The interest in this technique is based on the favourable radiobiological characteristics of prostate cancer and supported by advantageous logistic aspects deriving from short overall treatment time. The clinical validity of short-term treatment schedule is proven by a body of non-randomised studies, using both isocentric (LINAC-based) or non-isocentric (CyberKnife®-based) stereotactic body irradiation techniques. Twenty clinical studies, each enrolling more than 40 patients for a total of 1874 treated patients, were revised in terms of technological setting, toxicity, outcome and quality of life assessment. The implemented strategies for the tracking of the prostate and the sparing of the rectal wall have been investigated with particular attention. The urinary toxicity after prostate stereotactic body irradiation seems slightly more pronounced as compared to rectal adverse events, and this is more evident for late occurring events, but no worse as respect to conventional fractionation schemes. As far as the rate of severe acute toxicity is concerned, in all the available studies the treatment was globally well tolerated. While awaiting long-term data on efficacy and toxicity, the analysed studies suggest that the outcome profile of this approach, alongside the patient convenience and reduced costs, is promising. Forty-eight ongoing clinical trials are also presented as a preview of the expectation from the near future.

Analysis of Circulating Tumor Cells in Prostate Cancer Patients at PSA Recurrence and Review of the Literature.

BACKGROUND: Circulating tumor cells have been described in prostate cancer patients at diagnosis and in the metastatic phase but little is known on their role at biochemical PSA recurrence. PATIENTS AND METHODS: Patients radically cured with either prostatectomy or radiotherapy were sequentially included at PSA recurrence. The presence of CTCs was evaluated by the CellSearch system. RESULTS: Twenty-nine patients were accrued at PSA recurrence. Median PSA at recurrence was 7.2 ng/ml (range=3.86-51.0 ng/ml). The median time to PSA progression was 4.66 years (range=0.1-16 years). CTCs were detected in one patient (3%) with low numbers (1 CTC/7.5 ml). CONCLUSION: In patients radically cured for prostate cancer at biochemical recurrence, CTCs are detected at very low levels in a minority of patients. Further studies are required to investigate alternative methods of CTC detection and the possible role of the bone marrow pre-metastatic niche at biochemical recurrence.

Oral toxicity management in head and neck cancer patients treated with chemotherapy and radiation: Xerostomia and trismus (Part 2). Literature review and consensus statement.

Radiotherapy alone or in combination with chemotherapy and/or surgery is a well-known radical treatment for head and neck cancer patients. Nevertheless acute side effects (such as moist desquamation, skin erythema, loss of taste, mucositis etc.) and in particular late toxicities (osteoradionecrosis, xerostomia, trismus, radiation caries etc.) are often debilitating and underestimated. A multidisciplinary group of head and neck cancer specialists from Italy met in Milan with the aim of reaching a consensus on a clinical definition and management of these toxicities. The Delphi Appropriateness method was used for this consensus and external experts evaluated the conclusions. The paper contains 20 clusters of statements about the clinical definition and management of stomatological issues that reached consensus, and offers a review of the literature about these topics. The review was split into two parts: the first part dealt with dental pathologies and osteo-radionecrosis (10 clusters of statements), whereas this second part deals with trismus and xerostomia (10 clusters of statements).

Oral toxicity management in head and neck cancer patients treated with chemotherapy and radiation: Dental pathologies and osteoradionecrosis (Part 1) literature review and consensus statement.

Radiotherapy alone or in combination with chemotherapy and/or surgery is the typical treatment for head and neck cancer patients. Acute side effects (such as oral mucositis, dermatitis, salivary changes, taste alterations, etc.), and late toxicities in particular (such as osteo-radionecrosis, hypo-salivation and xerostomia, trismus, radiation caries etc.), are often debilitating. These effects tend to be underestimated and insufficiently addressed in the medical community. A multidisciplinary group of head and neck cancer specialists met in Milan with the aim of reaching a consensus on clinical definitions and management of these toxicities. The Delphi Appropriateness method was used for developing the consensus, and external experts evaluated the conclusions. This paper contains 10 clusters of statements about the clinical definitions and management of head and neck cancer treatment sequels (dental pathologies and osteo-radionecroses) that reached consensus, and offers a review of the literature about these topics. The review was split into two parts: the first part dealt with dental pathologies and osteo-radionecroses (10 clusters of statements), whereas this second part deals with trismus and xerostomia.