Management of radiation-induced oral mucositis in head and neck cancer patients: a real-life survey among 25 Italian radiation oncology centers.

AIM: Radiation-induced oral mucositis (RIOM) is the most frequent side effect in head and neck cancer (HNC) patients treated with curative radiotherapy (RT). A standardized strategy for preventing and treating RIOM has not been defined. Aim of this study was to perform a real-life survey on RIOM management among Italian RT centers. METHODS: A 40-question survey was administered to 25 radiation oncologists working in 25 different RT centers across Italy. RESULTS: A total of 1554 HNC patients have been treated in the participating centers in 2021, the majority (median across the centers 91%) with curative intent. Median treatment time was 41 days, with a mean percentage of interruption due to toxicity of 14.5%. Eighty percent of responders provide written oral cavity hygiene recommendations. Regarding RIOM prevention, sodium bicarbonate mouthwashes, oral mucosa barrier agents, and hyaluronic acid-based mouthwashes were the most frequent topic agents used. Regarding RIOM treatment, 14 (56%) centers relied on literature evidence, while internal guidelines were available in 13 centers (44%). Grade (G)1 mucositis is mostly treated with sodium bicarbonate mouthwashes, oral mucosa barrier agents, and steroids, while hyaluronic acid-based agents, local anesthetics, and benzydamine were the most used in mucositis G2/G3. Steroids, painkillers, and anti-inflammatory drugs were the most frequent systemic agents used independently from the RIOM severity. CONCLUSION: Great variety of strategies exist among Italian centers in RIOM management for HNC patients. Whether different strategies could impact patients' compliance and overall treatment time of the radiation course is still unclear and needs further investigation.

Increased Body Mass Index Is a Risk Factor for Poor Clinical Outcomes after Radical Prostatectomy in Men with International Society of Urological Pathology Grade Group 1 Prostate Cancer Diagnosed with Systematic Biopsies.

INTRODUCTION: The association between obesity and clinically significant prostate cancer (PCa) is still a matter of debate. In this study, we evaluated the effect of body mass index (BMI) on the prediction of pathological unfavorable disease (UD), positive surgical margins (PSMs), and biochemical recurrence (BCR) in patients with clinically localized (≤cT2c) International Society of Urological Pathology (ISUP) grade group 1 PCa at biopsy. METHODS: 427 patients with ISUP grade group 1 PCa who have undergone radical prostatectomy and BMI evaluation were included. The outcome of interest was the presence of UD (defined as ISUP grade group ≥3 and pT ≥3a), PSM, and BCR. RESULTS: Statistically significant differences resulted in comparing BMI with prostate-specific antigen (PSA) and serum testosterone levels (both p < 0.0001). Patients with UD and PSM had higher BMI values (p < 0.0001 and p = 0.006, respectively). BCR-free survival was significantly decreased in patients with higher BMI values (p < 0.0001). BMI was an independent risk factor for BCR and PSM. Receiver-operating characteristic analysis testing PSA accuracy in different BMI groups, showed that PSA had a reduced predictive value (area under the curve [AUC] = 0.535; 95% confidence interval [CI] = 0.422-0.646), in obese men compared to overweight (AUC = 0.664; 95% CI = 0.598-0.725) and normal weight patients (AUC = 0.721; 95% CI = 0.660-0.777). CONCLUSION: Our findings show that increased BMI is a significant predictor of UD and PSM at RP in patients with preoperative low-to intermediate-risk diseases, suggesting that BMI evaluation may be useful in a clinical setting to identify patients with favorable preoperative disease characteristics harboring high-risk PCa.

Prostate Cancer Radiogenomics-From Imaging to Molecular Characterization.

Radiomics and genomics represent two of the most promising fields of cancer research, designed to improve the risk stratification and disease management of patients with prostate cancer (PCa). Radiomics involves a conversion of imaging derivate quantitative features using manual or automated algorithms, enhancing existing data through mathematical analysis. This could increase the clinical value in PCa management. To extract features from imaging methods such as magnetic resonance imaging (MRI), the empiric nature of the analysis using machine learning and artificial intelligence could help make the best clinical decisions. Genomics information can be explained or decoded by radiomics. The development of methodologies can create more-efficient predictive models and can better characterize the molecular features of PCa. Additionally, the identification of new imaging biomarkers can overcome the known heterogeneity of PCa, by non-invasive radiological assessment of the whole specific organ. In the future, the validation of recent findings, in large, randomized cohorts of PCa patients, can establish the role of radiogenomics. Briefly, we aimed to review the current literature of highly quantitative and qualitative results from well-designed studies for the diagnoses, treatment, and follow-up of prostate cancer, based on radiomics, genomics and radiogenomics research.

SARS-CoV-2 Infection and High-Risk Non-Muscle-Invasive Bladder Cancer: Are There Any Common Features?

BACKGROUND: The new severe acute respiratory syndrome virus (SARS-CoV-2) outbreak is a huge health, social and economic issue and has been declared a pandemic by the World Health Organization. Bladder cancer, on the contrary, is a well-known disease burdened by a high rate of affected patients and risk of recurrence, progression and death. SUMMARY: The coronavirus disease (COVID-19 or 2019-nCoV) often involves mild clinical symptoms but in some cases, it can lead to pneumonia with acute respiratory distress syndrome and multiorgan dysfunction. Factors associated with developing a more severe disease are increased age, obesity, smoking and chronic underlying comorbidities (including diabetes mellitus). High-risk non-muscle-invasive bladder cancer (NMIBC) progression and worse prognosis are also characterized by a higher incidence in patients with risk factors similar to COVID-19. Immune system response and inflammation have been found as a common hallmark of both diseases. Most severe cases of COVID-19 and high-risk NMIBC patients at higher recurrence and progression risk are characterized by innate and adaptive immune activation followed by inflammation and cytokine/chemokine storm (interleukin [IL]-2, IL-6, IL-8). Alterations in neutrophils, lymphocytes and platelets accompany the systemic inflammatory response to cancer and infections. Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio for example have been recognized as factors related to poor prognosis for many solid tumors, including bladder cancer, and their role has been found important even for the prognosis of SARS-CoV-2 infection. Key Messages: All these mechanisms should be further analyzed in order to find new therapeutic agents and new strategies to block infection and cancer progression. Further than commonly used therapies, controlling cytokine production and inflammatory response is a promising field.

Beyond PSA: The Role of Prostate Health Index (phi).

BACKGROUND: Widespread use of prostate specific antigen (PSA) in screening procedures allowed early identification of an increasing number of prostate cancers (PCas), mainly including indolent cancer. Availability of different therapeutic strategies which have a very different impact on the patient's quality of life suggested a strong need for tools able to identify clinically significant cancer at diagnosis. Multi-parametric magnetic resonance showed very good performance in pre-biopsy diagnosis. However, it is an expensive tool and requires an experienced radiologist. In this context, a simple blood-based test is worth investigating. In this context, researchers focused their attention on the development of a laboratory test able to minimize overdiagnosis without losing the identification of aggressive tumors. RESULTS: Recent literature data on PCa biomarkers revealed a clear tendency towards the use of panels of biomarkers or a combination of biomarkers and clinical variables. Phi, the 4Kscore, and Stockholm3 as circulating biomarkers and the Mi-prostate score, Exo DX Prostate, and Select MD-X as urinary biomarker-based tests have been developed. In this scenario, phi is worthy of attention as a noninvasive test significantly associated with aggressive PCa. CONCLUSIONS: Literature data showed that phi had good diagnostic performance to identify clinically significant (cs) PCa, suggesting that it could be a useful tool for personalized treatment decision-making. In this review, phi potentialities, limitations, and comparisons with other blood- and urinary-based tests were explored.

Incidence of fatigue and low-dose corticosteroid use in prostate cancer patients receiving systemic treatment: a meta-analysis of randomized controlled trials.

BACKGROUND: Cancer-related fatigue (CRF) is a complex condition that is reported in > 50% of cancer patients. In men with castration-resistant prostate cancer (CRPC), CRF was reported in 12-21% of patients. Approved systemic therapy against CRPC is commonly administered in combination with androgen-deprivation treatment (ADT) and, in some cases, with daily, low-dose corticosteroids. Importantly, the use of low-dose corticosteroids is associated with multiple negative effects, including reduced muscle mass. On these grounds, we hypothesized that the chronic use of corticosteroids may increase the incidence of fatigue in patients with prostate cancer. METHODS: We reviewed all randomized trials published during the last 15 years conducted in patients with prostate cancer receiving systemic treatment and we performed a sub-group analysis to gather insights regarding the potential differences in the incidence of fatigue in patients receiving vs. not receiving daily corticosteroids as part of their systemic anti-neoplastic regimen. RESULTS: Overall, 22,734 men enrolled in prospective randomized phase II and III trials were evaluable for fatigue. Estimated pooled incidence of grade 1-2 fatigue was 30.89% (95% CI = 25.34-36.74), while estimated pooled incidence of grade 3-4 fatigue was reported in 3.90% (95% CI = 2.91-5.02). Sub-group analysis showed that grade 3-4 fatigue was approximately double in patients who received daily corticosteroids as part of their anti-neoplastic treatment (5.58; 95% CI = 4.33-6.98) vs. those who did not (2.67%; 95% CI = 1.53-4.11). CONCLUSION: Our findings highlight the need for ad hoc-designed prospective clinical trials to investigate whether the benefits associated with low-dose, daily corticosteroids outweigh the risks associated with corticosteroid-related adverse events such as fatigue.

An increased body mass index is associated with a worse prognosis in patients administered BCG immunotherapy for T1 bladder cancer.

PURPOSE: The body mass index (BMI) may be associated with an increased incidence and aggressiveness of urological cancers. In this study, we aimed to evaluate the impact of the BMI on survival in patients with T1G3 non-muscle-invasive bladder cancer (NMIBC). METHODS: A total of 1155 T1G3 NMIBC patients from 13 academic institutions were retrospectively reviewed and patients administered adjuvant intravesical Bacillus Calmette-Guérin (BCG) immunotherapy with maintenance were included. Multivariable Cox regression analysis was performed to identify factors predictive of recurrence and progression. RESULTS: After re-TURBT, 288 patients (27.53%) showed residual high-grade NMIBC, while 867 (82.89%) were negative. During follow-up, 678 (64.82%) suffered recurrence, and 303 (30%) progression, 150 (14.34%) died of all causes, and 77 (7.36%) died of bladder cancer. At multivariate analysis, tumor size (hazard ratio [HR]:1.3; p = 0.001), and multifocality (HR:1.24; p = 0.004) were significantly associated with recurrence (c-index for the model:55.98). Overweight (HR: 4; p < 0.001) and obesity (HR:5.33 p < 0.001) were significantly associated with an increased risk of recurrence. Addition of the BMI to a model that included standard clinicopathological factors increased the C-index by 9.9. For progression, we found that tumor size (HR:1.63; p < 0.001), multifocality (HR:1.31; p = 0.01) and concomitant CIS (HR: 2.07; p < 0.001) were significant prognostic factors at multivariate analysis (C-index 63.8). Overweight (HR: 2.52; p < 0.001) and obesity (HR: 2.521 p < 0.001) were significantly associated with an increased risk of progression. Addition of the BMI to a model that included standard clinicopathological factors increased the C-index by 1.9. CONCLUSIONS: The BMI could have a relevant role in the clinical management of T1G3 NMIBC, if associated with bladder cancer recurrence and progression. In particular, this anthropometric factor should be taken into account at initial diagnosis and in therapeutic strategy decision making.

Stereotactic body radiation therapy for mediastinal lymph node metastases: how do we fly in a 'no-fly zone'?

PURPOSE: To evaluate the treatment-induced toxicity (as primary endpoint) and the efficacy (as secondary endpoint) of stereotactic body radiation therapy (SBRT) in the treatment of mediastinal lymph nodes (LNs) in the so-called no-fly zone (NFZ) in cancers with various histology. MATERIAL AND METHODS: Forty-two patients were retrospectively analyzed. Institutional dose/volume constraints for organs at risk (OARs) derived by published data were strictly respected. The correlation between treatment-related variables and toxicity was investigated by logistic regression, Chi-squared test or Fisher's exact test. Overall survival (OS), cause-specific survival (CSS), progression-free survival (PFS) and local control (LC) were collected from the follow-up reports. The impact of potential predictive factors on LC, PFS and OS were estimated by Cox proportional-hazard regression. RESULTS: Median follow-up time was 16 months (range 1-41). Four patients had esophageal G1 toxicity. Ten and six patients had G1 and G2 pulmonary toxicity, respectively. Treatment site and irradiation technique were significantly correlated with G ≥ 2 and G ≥ 1 toxicity, respectively. OS probability at 19 months was 88.3% and corresponded to CSS. LC probability at 16 months was 66.3% (median LC duration: 22 months, range 1-41). Fifteen patients (35.7%) were disease-free at 25 months (median time, range 1-41). The biologically effective dose (BED) and the target dose coverage indexes were significantly correlated with LC. CONCLUSIONS: SBRT can be considered as a safe treatment option for selected patients with oligo-metastases/recurrences in the NFZ, if strict dose/volume constraints are applied.

External radiotherapy for breast cancer in the elderly.

BACKGROUND: Breast cancer is the most common malignancy amongst elderly women and the main cause of mortality. A specific management for elderly woman is not clear because clinical trials are usually not customized for this subset of patients. AIMS: The aim of this paper is to provide an overview of the available information on the main issues in the field of breast cancer radiotherapy in the elderly population. MATERIALS AND METHODS: Authors discuss on different radiation treatments for breast cancer in the elderly, based on the data of the literature with a focus on new strategy: hypo-fractionation, accelerated partial breast irradiation, and the utility of a dose boost. DISCUSSION: The treatment of breast cancer is not standardized in the elderly. The optimal management in this population often requires complex multidisciplinary supportive care due to multiple comorbidities to optimize their cancer care. CONCLUSIONS: New options such as APBI or HyRT regimens should be taken into consideration and offered as a breach of duty to the elderly population. Furthermore, they should be extensively investigated through randomized clinical trials.

Tomotherapy concomitant with cetuximab, followed by cetuximab as single-agent therapy for unresectable squamous cell carcinoma of the skin: a case report.

BACKGROUND: Cutaneous squamous cell carcinoma (SCC) is the second most frequency of all skin tumors. Incidence of SCC has risen significantly due to an increased sun exposure and the number of immunodeficient patients. Cutaneous SCC is characterized by high Epidermal growth factor receptor (EGFR) expression with low frequency of RAS mutations. Generally, locoregional surgery is curative and systemic therapy is not indicated. We evaluated the activity and toxicity profile of tomotherapy concomitant with Cetuximab, followed by Cetuximab as single agent therapy in a patient affected by unresectable, locally advanced cutaneous SCC. CASE PRESENTATION: At our institution, on March 2012 we treated a 45 years-old patient affected by locally advanced, unresectable G1 SCC of the lumbar region. At our first observation, the patient was asthenic, with severe pain and functional limitations. There was also a superinfection due to Pseudomonas Aeruginosa resistant to antibiotics, and a G3 anemia secondary to the bleeding lesion. ECOG Performance Status was 2. Tomotherapy has been performed concomitant with the Cetuximab (400 mg/m2, followed by weekly doses of 250 mg/m2) at the total dose of 60 Gy (2 Gy/fx), followed by Cetuximab monotherapy.The lesion reduced progressively until disappear even after the suspension of the treatment and the patient achieved complete response. Toxicity resulted in G1 cutaneous rash and G2 toxicity to the nails, appeared after 5 months of treatment, typical toxicity profile of the anti-EGFR therapies. After one month of therapy the Pseudomonas Aeruginosa superinfection totally disappeared. Quality of life resulted significantly improved with reduction until discontinuation of the anti-pain drugs, and progressive increase of the hemoglobin levels. At follow up of 15 months there was no evidence of active disease and the ECOG Performance Status was 0 (zero). CONCLUSION: The treatment was effective and feasible. Considering these excellent results, further studies about concomitant tomotherapy with Cetuximab for advanced/inoperable SCC of the skin are needed.

Reliability of Multiparametric Magnetic Resonance Imaging in Patients with a Previous Negative Biopsy: Comparison with Biopsy-Naïve Patients in the Detection of Clinically Significant Prostate Cancer.

Background: Multiparametric magnetic resonance is an established imaging utilized in the diagnostic pathway of prostate cancer. The aim of this study is to evaluate the accuracy and reliability of multiparametric magnetic resonance imaging (mpMRI) in the detection of clinically significant prostate cancer, defined as Gleason Score ≥ 4 + 3 or a maximum cancer core length 6 mm or longer, in patients with a previous negative biopsy. Methods: The study was conducted as a retrospective observational study at the University of Naples "Federico II", Italy. Overall, 389 patients who underwent systematic and target prostate biopsy between January 2019 and July 2020 were involved and were divided into two groups: Group A, which included biopsy-naïve patients; Group B, which included re-biopsy patients. All mpMRI images were obtained using three Tesla instruments and were interpreted according to PIRADS (Prostate Imaging Reporting and Data System) version 2.0. Results: 327 patients were biopsy-naïve, while 62 belonged to the re-biopsy group. Both groups were comparable in terms of age, total PSA (prostate-specific antigen), and number of cores obtained at the biopsy. 2.2%, 8.8%, 36.1%, and 83.4% of, respectively, PIRADS 2, 3, 4, and 5 biopsy-naïve patients reported a clinically significant prostate cancer compared to 0%, 14.3%, 39%, and 66.6% of re-biopsy patients (p < 0.0001-p = 0.040). No difference was reported in terms of post-biopsy complications. Conclusions: mpMRI confirms its role as a reliable diagnostic tool prior to performing prostate biopsy in patients who underwent a previous negative biopsy, reporting a comparable detection rate of clinically significant prostate cancer.

Quality of Life and Psychological Distress among Patients with Small Renal Masses.

Background: Quality of life (QoL) and psychological distress represent an important aspect of the daily life of cancer patients. The aim of this systematic review was to critically analyze available literature regarding QoL and psychological distress in patients with small renal masses (SRMs). (2) Methods: A systematic search of EMBASE, PUBMED and American Psychological Association (APA-net) was performed on 30 April 2022. Studies were considered eligible if they included patients with SRMs, had a prospective or retrospective design, included at least 10 patients, were published in the last 20 years, and assessed the QoL or psychological distress in patients that underwent active surveillance (AS) in comparison to those that underwent ablation/surgery treatments. (3) Results: The patients that underwent AS were statistically significantly older, with smaller renal masses than those that underwent surgery/ablation. A study showed a significant reduction in total scores of Short Form-12 (SF-12) among AS patients when compared to partial nephrectomy (PN) patients at enrollment (95.0 ± 15.8 vs. 99.1 ± 13.9), 2 years (91.0 ± 16.4 vs. 100.3 ± 14.3), and at 3 years (92.9 ± 15.9 vs. 100.3 ± 14.3), p < 0.05, respectively. That was mainly due to lower physical health scores. On the other hand, another study showed that AS patients with a biopsy-proven malignant tumor had a worse psychological distress sub-score (PDSS) compared to patients treated with surgery/ablation after biopsy. (4) Conclusions: It seems that there is an influence on QoL and psychological distress while on AS of SMRs. However, due to the low amount of available data, the impact of AS or active treatment on QoL or psychological distress of patients with small renal masses warrants further investigation.

SBRT for Localized Prostate Cancer: CyberKnife vs. VMAT-FFF, a Dosimetric Study.

In recent years, stereotactic body radiation therapy (SBRT) has gained popularity among clinical methods for the treatment of medium and low risk prostate cancer (PCa), mainly as an alternative to surgery. The hypo-fractionated regimen allows the administration of high doses of radiation in a small number of fractions; such a fractionation is possible by exploiting the different intrinsic prostate radiosensitivity compared with the surrounding healthy tissues. In addition, SBRT treatment guaranteed a better quality of life compared with surgery, avoiding risks, aftermaths, and possible complications. At present, most stereotactic prostate treatments are performed with the CyberKnife (CK) system, which is an accelerator exclusively dedicated for stereotaxis and it is not widely spread in every radiotherapy centre like a classic linear accelerator (LINAC). To be fair, a stereotactic treatment is achievable also by using a LINAC through Volumetric Modulated Arc Therapy (VMAT), but some precautions must be taken. The aim of this work is to carry out a dosimetric comparison between these two methodologies. In order to pursue such a goal, two groups of patients were selected at Instituto Nazionale Tumori-IRCCS Fondazione G. Pascale: the first group consisting of ten patients previously treated with a SBRT performed with CK; the second one was composed of ten patients who received a hypo-fractionated VMAT treatment and replanned in VMAT-SBRT flattening filter free mode (FFF). The two SBRT techniques were rescaled at the same target coverage and compared by normal tissue sparing, dose distribution parameters and delivery time. All organs at risk (OAR) constraints were achieved by both platforms. CK exhibits higher performances in terms of dose delivery; nevertheless, the general satisfying dosimetric results and the significantly shorter delivery time make VMAT-FFF an attractive and reasonable alternative SBRT technique for the treatment of localized prostate cancer.

Modified Glasgow Prognostic Score as a Predictor of Recurrence in Patients with High Grade Non-Muscle Invasive Bladder Cancer Undergoing Intravesical Bacillus Calmette-Guerin Immunotherapy.

BACKGROUND: A systemic inflammatory marker, the modified Glasgow prognostic score (mGPS), could predict outcomes in non-muscle-invasive bladder cancer (NIMBC). We aimed to investigate the predictive power of mGPS in oncological outcomes in HG/G3 T1 NMIBC patients undergoing Bacillus Calmette-Guérin (BCG) therapy. METHODS: We retrospectively reviewed patient's medical data from multicenter institutions. A total of 1382 patients with HG/G3 T1 NMIBC have been administered adjuvant intravesical BCG therapy, every week for 3 weeks given at 3, 6, 12, 18, 24, 30 and 36 months. The analysis of mGPS for recurrence and progression was performed using multivariable and univariable Cox regression models. RESULTS: During follow-up, 659 patients (47.68%) suffered recurrence, 441 (31.91%) suffered progression, 156 (11.28%) died of all causes, and 67 (4.84%) died of bladder cancer. At multivariable analysis, neutrophil to lymphocyte ratio [hazard ratio (HR): 7.471; p = 0.0001] and erythrocyte sedimentation rate (ESR) (HR: 0.706; p = 0.006 were significantly associated with recurrence. mGPS has no statistical significance for progression (p = 0.076). Kaplan-Meier survival analysis showed a significant difference in survival among patients from different mGPS subgroups. Five-year OS was 93% (CI 95% 92-94), in patients with mGPS 0, 82.2% (CI 95% 78.9-85.5) in patients with mGPS 1 and 78.1% (CI 95% 60.4-70) in mGPS 2 patients. Five-year CSS was 98% (CI 95% 97-99) in patients with mGPS 0, 90% (CI 95% 87-94) in patients with mGPS 1, and 100% in mGPS 2 patients. Limitations are applicable to a retrospective study. CONCLUSIONS: mGPS may have the potential to predict recurrence in HG/G3 T1 NMIBC patients, but more prospective, with large cohorts, studies are needed to study the influence of systemic inflammatory markers in prediction of outcomes in NMIBC for a definitive conclusion.

Association of statin use and oncological outcomes in patients with first diagnosis of T1 high grade non-muscle invasive urothelial bladder cancer: results from a multicenter study.

BACKGROUND: We aimed to test the hypothesis that the immune-modulatory effect of statins may improve survival outcomes in patients with non-muscle invasive bladder cancer (NMIBC). We focused on a cohort of patients diagnosed with high risk NMIBC, that were treated with intravesical BCG immunotherapy. METHODS: We included patients at first diagnosis of T1 high grade NMIBC after transurethral resection of bladder (TURB). All procedures were performed at 18 different tertiary institutions between January 2002 and December 2012. Univariable and multivariable models were used to test differences in terms of residual tumor, disease recurrence, disease progression and overall mortality (OM) rates. RESULTS: Overall, 1510 patients with T1 high grade NMIBC at TURB were included in our analyses. Of these, 402 (26.6%) were statin users. At multivariable analysis, statin use was associated with a higher rate of high-grade BC at re-TURB (OR: 1.37, 95%CI: 1.04-1.78; P=0.022), while at follow-up it was not independently associated with OM (HR: 0.71, 95%CI: 0.50-1.03; P=0.068) and disease progression rates (HR: 0.97, 95%CI: 0.79-1.19; P=0.753). Conversely, statin use has been shown to be independently associated with a lower risk of recurrence (HR:0.80, 95%CI: 0.67-0.95; P=0.009). The median recurrence-free survival was 47 (95%CI 40-49) months for those classified as non-statin users vs. 53 (95%CI 48-68) months in those classified as statin users. CONCLUSIONS: Statin daily intake do not compromise oncological outcomes in high risk NMIBC patients treated with BCG. Moreover, statin may have a beneficial effect on recurrence rates in this cohort of patients.

Systemic combining inflammatory score (SCIS): a new score for prediction of oncologic outcomes in patients with high-risk non-muscle-invasive urothelial bladder cancer.

BACKGROUND: An accurate and early diagnosis of bladder cancer (BC) is essential to offer patients the most appropriate treatment and the highest cure rate. For this reason, patients need to be best stratified by class and risk factors. We aimed to develop a score able to better predict cancer outcomes, using serum variables of inflammation. METHODS: A total of 1,510 high-risk non-muscle invasive bladder cancer (NMIBC) patients were included in this retrospective observational study. Patients with pathologically proven T1 HG/G3 at first TURBT were included. Systemic combined inflammatory score (SCIS) was calculated according to systemic inflammatory markers (SIM), modified Glasgow prognostic score (mGPS), and prognostic nutritional index (PNI) dichotomized (final score from 0 to 3). RESULTS: After 48 months of follow-up (IQR 40.0-73.0), 727 patients recurred (48.1%), 485 progressed (32.1%), 81 died for cancer (7.0%), and 163 died for overall causes (10.8%). Overall, 231 (15.3%) patients had concomitant Cis, 669 (44.3%) patients had multifocal pathology, 967 (64.1%) patients had tumor size >3 cm. Overall, 357 (23.6%) patients received immediate-intravesical therapy, 1,356 (89.8%) received adjuvant intravesical therapy, of which 1,382 (91.5%) received BCG, 266 (17.6%) patients received mitomycin C, 4 (0.5%) patients received others intravesical therapy. Higher SCIS was independently predictive of recurrence (hazard ratio HR 1.5, 1.3 and 2.2) and cancer specific mortality for SCIS 0 and 3 (HR: 1.61 and 2.3), and overall mortality for SCIS 0 and 3 (HR: 2.4 and 3.2). Conversely, SCIS was not associated with a higher probability of progression. CONCLUSIONS: The inclusion of the SCIS in clinical practice is simple to apply and can help improve the prediction of cancer outcomes. It can identify patients with high-grade BC who are more likely to experience disease mortality.

Three vs. Four Cycles of Neoadjuvant Chemotherapy for Localized Muscle Invasive Bladder Cancer Undergoing Radical Cystectomy: A Retrospective Multi-Institutional Analysis.

BACKGROUND: Three or four cycles of cisplatin-based chemotherapy is the standard neoadjuvant treatment prior to cystectomy in patients with muscle-invasive bladder cancer. Although NCCN guidelines recommend 4 cycles of cisplatin-gemcitabine, three cycles are also commonly administered in clinical practice. In this multicenter retrospective study, we assessed a large and homogenous cohort of patients with urothelial bladder cancer (UBC) treated with three or four cycles of neoadjuvant cisplatin-gemcitabine followed by radical cystectomy, in order to explore whether three vs. four cycles were associated with different outcomes. METHODS: Patients with histologically confirmed muscle-invasive UBC included in this retrospective study had to be treated with either 3 (cohort A) or 4 (cohort B) cycles of cisplatin-gemcitabine as neoadjuvant therapy before undergoing radical cystectomy with lymphadenectomy. Outcomes including pathologic downstaging to non-muscle invasive disease, pathologic complete response (defined as absence of disease -ypT0), overall- and cancer-specific- survival as well as time to recurrence were compared between cohorts A vs. B. RESULTS: A total of 219 patients treated at 14 different high-volume Institutions were included in this retrospective study. Patients who received 3 (cohort A) vs. 4 (cohort B) cycles of neoadjuvant cisplatin-gemcitabine were 160 (73,1%) vs. 59 (26,9%).At univariate analysis, the number of neoadjuvant cycles was not associated with either pathologic complete response, pathologic downstaging, time to recurrence, cancer specific, and overall survival. Of note, patients in cohort B vs. A showed a worse non-cancer specific overall survival at univariate analysis (HR= 2.53; 95 CI= 1.05 - 6.10; p=0.046), although this finding was not confirmed at multivariate analysis. CONCLUSIONS: Our findings suggest that 3 cycles of cisplatin-gemcitabine may be equally effective, with less long-term toxicity, compared to 4 cycles in the neoadjuvant setting.

The role of radiation therapy and systemic therapies in elderly with breast cancer.

The focus of this review deals with the management of elderly patients with early stage breast cancer, discussing the role of systemic therapies [endocrine therapy (ET), chemotherapy, novel agents] and radiation therapy (RT). Several studies have evaluated in elderly low risk patients the possibility of omitting the RT but, at the same time, higher locoregional relapse (LR) rates without significant impact on overall survival (OS) were observed in all studies when RT was excluded. Technological improvements [intensity-modulated RT (IMRT), volumetric modulated arc therapy (VMAT), high dose brachy therapy (HDBT)] are very useful in order to reduce cosmetic outcome and improve quality of life of frail patients. The optimal sequence of ET, concomitant or sequential to RT, is currently under investigation, and specifically in the elderly it is questioned the possible choice of prolonged therapy after standard 5 years. Data regarding chemotherapy suggesting no benefit of OS in endocrine responsive diseases, whereas endocrine non-responsive breast cancer still showed a better outcome. Cyclophosphamide, methotrexate and 5-fluorouracil (CMF) regimen is recognized as the standard protocol, although age-dependent increase in therapy related mortality was reported. Neoadjuvant chemotherapy in elderly showed a lower ratio of pathological complete response in comparison to younger patients, but triple negative breast cancer patients showed a good prognosis regarding OS, comparable to younger patients. The risk of cardiotoxicity seems to increase with age, so the use trastuzumab in this setting is much debated. Currently, other anti-HER2 agents (pertuzumab, lapatinib) are used in neoadjuvant setting, but the data on elderly are still premature. Novel molecules are rapidly changing the clinical management of breast cancer patients but are tested especially in locally advanced and metastatic setting. Among these, particularly interesting are inhibitors of CDK4 and 6, alpelisib (PI3K enzymes mutations), immune checkpoint (PD1, PDL1, CTLA4) inhibitors, atezolizumab. Elderly patients are under-represented in clinical trials, although ageing can be frequently correlated with a decrease in the effectiveness of the immune system. For elderly women, treatment decisions should be individually decided, taking into account the geriatric assessment and limited life expectancy and tumor characteristics.

Dosimetric comparison among cyberknife, helical tomotherapy and VMAT for hypofractionated treatment in localized prostate cancer.

Hypofractionation for localized prostate cancer treatment is rapidly spreading in the medical community and it is supported by radiobiological evidences (lower α/ß ratio compared with surrounding tissues). Stereotactic body radiation therapy (SBRT) is a technique to administer high doses with great precision, which is commonly performed with CyberKnife (CK) in prostate cancer treatment. Since the CyberKnife (CK) is not available at all radiotherapy center, alternative SBRT techniques are available such as Volumetric Modulated Arc Therapy (VMAT) and Helical Tomotherapy (HT). The aim of the present study was to compare the dosimetric differences between the CK, VMAT, and HT plans for localized prostate cancer treatment.Seventeenpatients have been recruited and replanned using VMAT and HT to this purpose: they received the treatment using the CK with a prescription of 36.25 Gy in 5 fractions; bladder, rectum and penis bulb were considered as organs at risk (OAR). In order to compare the techniques, we considered DVHs, PTV coverage, Conformity Index and new Conformity Index, Homogeneity Index, beam-on time and OARs received dose.The 3 treatments methods showed a comparable coverage of the lesion (PTV 95%: 99.8 ± 0.4% CK; 98.5 ± 0.8% VMAT; 99.4 ±â€Š0.5% HT. P < .05) and good sparing of OARs. Nevertheless, the beam-on time showed a significant difference (37 ±â€Š9 m CK; 7.1 ±â€Š0.3 m VMAT; 17 ±â€Š2 m HT. P < .05).Our results showed that, although CK is the best SBRT technique for prostate cancer treatment, in case this technology is not available, it can be replaced by a similar treatment delivered by VMAT technique. VMAT can be administrated only if it has an appropriate Image Guided Radiation Therapy (IGRT) tracking system.

Soft tissue necrosis in patients treated with transoral robotic surgery and postoperative radiotherapy: preliminary results.

OBJECTIVE: Postoperative radiotherapy (PORT) is indicated in almost two-thirds of patients treated with transoral robotic surgery (TORS) for head and neck tumors. The aim of this study was to quantify the toxicity profile of patients treated with PORT after TORS in oropharyngeal and supraglottic laryngeal cancer focusing on soft tissue necrosis (STN). METHODS: We retrospectively reviewed 28 patients. Acute and late toxicity were examined. Incidence and severity of STN were recorded. RESULTS: No patient experienced acute grade 3 skin or mucosal toxicity; 1 patient had grade 3 dysphagia. At 12 months, no evaluated patient required enteral nutrition and 2 patients had tracheostomy. STN occurred in 4 (14%) patients: 3 out of 4 (75%) patients with STN had diabetes, whereas 6 out of 13 (25%) patients without STN had diabetes (p = 0.05). CONCLUSION: We found an acceptable toxicity profile of PORT performed after a TORS procedure. Diabetes mellitus might be a risk factor for STN.