Intravesical device-assisted therapies for non-muscle-invasive bladder cancer.

Non-muscle-invasive bladder cancer (NMIBC), the most prevalent type of bladder cancer, accounts for ~75% of bladder cancer diagnoses. This disease has a 50% risk of recurrence and 20% risk of progression within 5 years, despite the use of intravesical adjuvant treatments (such as BCG or mitomycin C) that are recommended by clinical guidelines. Intravesical device-assisted therapies, such as radiofrequency-induced thermochemotherapeutic effect (RITE), conductive hyperthermic chemotherapy, and electromotive drug administration (EMDA), have shown promising efficacy. These device-assisted treatments are an attractive alternative to BCG, as issues with supply have been a problem in some countries. RITE might be an effective treatment option for some patients who have experienced BCG failure and are not candidates for radical cystectomy. Data from trials using EMDA suggest that it is effective in high-risk disease but requires further validation, and results of randomized trials are eagerly awaited for conductive hyperthermic chemotherapy. Considerable heterogeneity in patient cohorts, treatment sessions, use of maintenance regimens, and single-arm study design makes it difficult to draw solid conclusions, although randomized controlled trials have been reported for RITE and EMDA.

Radiation dose intensification in pre-operative chemo-radiotherapy for locally advanced rectal cancer

Background. To assess the role of radiation dose intensification with simultaneous integrated boost guided by 18-FDG-PET/CT in pre-operative chemo-radiotherapy (ChT-RT) for locally advanced rectal cancer. Methods. A prospective study was approved by the Internal Review Board. Inclusion criteria were: age >18 years old, World Health Organization performance status of 0-1, locally advanced histologically proven adenocarcinoma of the rectum within 10 cm of the anal verge, signed specific informed consent. High-dose volumes were defined including the hyper-metabolic areas of 18-FDG-PET/CT of primary tumor and the corresponding mesorectum and/or pelvic nodes with at least a standardized uptake values (SUV) of 5. A dose of 60 Gy/30 fractions was delivered. A total dose of 54 Gy/30 fractions was delivered to prophylactic areas. Capecitabine was administered concomitantly with RT for a dose of 825 mg/mq twice daily for 5 days/every week. Results. Between September 2011 and July 2015 fortypatients were recruited. At the time of the analysis, median follow up was 20 months (range 5-51). The median interval from the end of ChT-RT to surgery was 9 weeks (range 8-12). Thirty-seven patients (92.5 %) were submitted to sphincter preservation. Tumor Regression Grade (Mandard scale) was recorded as follows: grade 1 in 7 (17.5 %), grade 2 in 17 (42.5 %), grade 3 in 15 (37.5 %) and grade 4 in 1 (2.5 %). Post-surgical circumferential resection margin was negative in all patients. A tumor downstaging was reported in 62.5 % (95 % CI: 0.78-0.47). A nodes downstaging was registered in 85 % (95 % CI: 0.55-0.25). 18-FDG-PET/CT was not able to predict pCR. No correlation was found between pre-treatment SUV-max values and pCR. A metabolic tumor volume >127 cc was related to ypT ≥2 (p 0.01). Patients with TRG >2 had higher tumor lesion glycolysis values (p 0.05). Conclusion. Preliminary results did not confirm some advantages in terms of primary tumor downstaging/downsizing compared to conventional schedules reported in historical series. The role of 18-FDG-PET/CT in neoadjuvant rectal cancer management needs to be confirmed in further investigations. Long terms results are necessary (AU)

No disponible

Dosimetric predictors of acute hematologic toxicity during concurrent intensity-modulated radiotherapy and chemotherapy for anal cancer

Purpose. This study aimed at investigating whether the irradiated volume of pelvic bone marrow (PBM) and specific subsites may predict the occurrence of acute hematologic toxicity (HT) in anal cancer patients undergoing concurrent chemo-radiation. Methods. 50 patients, submitted to IMRT and concurrent chemotherapy, were analyzed. Several bony structures were defined on planning-CT: PBM and lumbar-sacral (LSBM), lower pelvis (LPBM) and iliac (IBM) bone marrow. On dose-volume histograms, dosimetric parameters were taken. Endpoints included white blood-cell-count (WBC), absolute-neutrophil-count (ANC), hemoglobin (Hb) and platelet nadirs and acute hematologic toxicity (HT) according to RTOG scoring scale. Generalized linear modeling was used to find correlations between dosimetric variables and blood cell nadirs, while logistic regression analysis was used to test correlation with ≥G3 HT. Receiver Operating Characteristic (ROC) curve analysis was used to evaluate the optimal cut-off points for predictive dosimetric variables with the Youden method. Results. Maximum detected acute HT comprised 38 % of ≥G3 leukopenia and 32 % of ≥G3 neutropenia. Grade 2 anemia was observed in 4 % of patients and ≥G3 thrombocytopenia in 10 %. On multivariate analysis a higher PBM-V20 was associated with lower WBC nadir. Increased LSBM-V40 was correlated with a higher likelihood to develop ≥G3 HT. A cut-off point at 41 % for LSBM-V40 was found. Patients with LSBM-V40 ≥41 % were more likely to develop ≥G3 HT (55.3 vs. 32.4 %; p < 0.01). Conclusions. Increased low-dose to pelvic bony structures significantly predicted for WBC decrease. Medium-high dose to specific osseous subsites was associated with a higher probability of HT. LSBM-V40 was a strong predictor of ≥G3 HT. A threshold at 41 % for LSBM-V40 could be used to limit HT (AU)

No disponible

Trans-arterial radioembolization in intermediate-advanced hepatocellular carcinoma: systematic review and meta-analyses.

Trans-arterial radioembolization (TARE) is a recognized, although not explicitly recommended, experimental therapy for unresectable hepatocellular carcinoma (HCC).A systematic literature review was performed to identify published studies on the use of TARE in intermediate and advanced stages HCC exploring the efficacy and safety of this innovative treatment.Twenty-one studies reporting data on overall survival (OS) and time to progression (TTP), were included in a meta-analysis. The pooled post-TARE OS was 63% (95% CI: 56-70%) and 27% (95% CI: 21-33%) at 1- and 3-years respectively in intermediate stage HCC, whereas OS was 37% (95% CI: 26-50%) and 13% (95% CI: 9-18%) at the same time intervals in patients with sufficient liver function (Child-Pugh A-B7) but with an advanced HCC because of the presence of portal vein thrombosis. When an intermediate and advanced case-mix was considered, OS was 58% (95% CI: 48-67%) and 17% (95% CI: 12-23%) at 1- and 3-years respectively. As for TTP, only four studies reported data: the observed progression probability was 56% (95% CI: 41-70%) and 73% (95% CI: 56-87%) at 1 and 2 years respectively. The safety analysis, focused on the risk of liver decompensation after TARE, revealed a great variability, from 0-1% to more than 36% events, influenced by the number of procedures, patient Child-Pugh stage and treatment duration.Evidence supporting the use of radioembolization in HCC is mainly based on retrospective and prospective cohort studies. Based on this evidence, until the results of the ongoing randomized trials become available, radioembolization appears to be a viable treatment option for intermediate-advanced stage HCC.

Concurrent chemo-radiotherapy in elderly patients: tolerance and compliance in a series of 137 patients

Introduction: Aggressive cancer treatment is a challenge in elderly patients. The present study aims to assess tolerance in terms of acute toxicity and compliance of concurrent chemo-radiotherapy (cCRT) in a series of patients aged C70 years. Materials and methods Clinical: records of patients aged C70 years who underwent cCRT between January 2005 and December 2013 were reviewed. Concurrent CRT had curative intent in 134 patients (97.8 %) and palliative intent in 3 patients (2.2 %). Chemotherapy (CT) drugs and schedule were selected according to tumor histology. Radiotherapy median dose was 45.0 Gy (range 11-70 Gy) for curative purposes and 54 Gy (range 40-56 Gy) for palliative purposes. Incidence of acute toxicity and compliance to cCRT were analyzed and correlated with age, Karnofsky Performance Status (KPS), and Charlson Comorbidity Index (CCI). Results: Overall, 137 patients, 82 males (60 %) and 55 females (40 %), median age 74 years (range 70–90 years) were analyzed. Concurrent CRT schedule was completed by 132 patients (96.4 %). Thirty-one of these patients (23.5 %) temporarily interrupted treatment. Hematological toxicity with grade C1 was observed in 25 patients (18.2 %), gastrointestinal toxicity in 55 (40.1 %), and genitourinary in 13 (9.5 %). Mucositis with grade C1 was recorded in 19 patients (13.9 %). No statistical significant correlation between KPS, CCI, and toxicity was found. A correlation trend between mucositis and patient age (p = 0.05) was observed. Conclusion: Concurrent CRT for elderly was feasible and quite well tolerated. Great attention in prescribing CT dose should be paid to limit acute toxicity (AU)

No disponible

Mediastinal small cell carcinoma: a unique clinical entity?

Purpose: Mediastinal small cell carcinoma (MSCC) is a rare tumor with limited published literature. In view of diagnostic confusion pertaining to this tumor, we investigated its origin, clinical features, management and survival. Methods: Clinical data of MSCC patients were retrospectively reviewed. Eligible patients showed pathologically proven small cell carcinoma (SCC) with the primary lesions confined to the mediastinum. Survival information was collected through follow-up studies. Results: Among 25 MSCC patients identified, 22 were classified to have limited disease (LD), while 3 were with extensive disease (ED). The 5 patients (20 %) underwent surgery and 20 patients (80 %) underwent non-surgical treatment. The 4 patients with LD MSCC received chemotherapy alone, while 13 of them received chemoradiotherapy. Overall median survival time (MST) of all patients was 22 months, and the 1-, 3- and 5-year overall survival rates were 67.4, 16.8, and 8.4 %, respectively. The MST of LD and ED patients separately was 23 and 8 months, respectively, with significant difference (P = 0.005). But, the MST of patients who received surgical and non-surgical treatment was 25 and 21 months, respectively, with no significant difference (P = 0.757). The MST of LD patients receiving chemotherapy and chemoradiotherapy was 12 and 29 months, respectively, but somehow did not show significant difference (P = 0.482). Conclusions: Our data suggested that MSCC may be a separate clinical entity like extrapulmonary small cell carcinomas (EPSCCs). Despite, multimodal treatment is currently the main treatment option, but for patients with LD MSCC, chemoradiotherapy is recommended to be preferred treatment modality (AU)

No disponible

Serum human epididymis protein 4 is associated with the treatment response of concurrent chemoradiotherapy and prognosis in patients with locally advanced non-small cell lung cancer

Aim: To investigate the role of human epididymis protein 4 (HE4) in the diagnosis and prognosis of patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving concurrent chemoradiotherapy (CRT). Methods: A total of 218 patients with LA-NSCLC were enrolled. All patients underwent CRT. The treatment response to CRT was evaluated. The prognosis analysis was performed using relapse-free survival (RFS) and overall survival [1]. Results: Our data show that the serum HE4 can discriminate patients who respond well to CRT from those who respond poorly. Higher serum HE4 had dramatically increased risk of being non-responders to CRT. Serum HE4 level is also associated with prognosis of patients after CRT. Patients with high HE4 level had shorter RFS and OS compared to those with low HE4 level. Conclusion: Our data suggest that serum HE4 may be a useful prognostic biomarker for LA-NSCLC patients who underwent CRT (AU)

No disponible

Concurrent radiotherapy with S-1 plus cisplatin versus concurrent radiotherapy with cisplatin alone for the treatment of locally advanced cervical carcinoma: a pilot randomised controlled trial

Background: In the present study, we compared the efficacy and safety of concurrent radiotherapy with S-1 plus cisplatin (CRSC) versus concurrent radiotherapy with cisplatin alone (CRC) for the treatment of advanced cervical carcinoma (ACC). Methods: Between February 2006 and January 2009, 72 eligible patients with ACC were included and randomly divided into two groups. Thirty-six patients received CRSC with radiotherapy (60 Gy/30 fractions over 6 weeks) beginning on day 1, S-1 (according to body surface area) for 28 days repeated every 6 weeks, and cisplatin (50 mg/ m2, intravenously on day 1) every 4 weeks for two cycles. The other 36 received CRC at the same cisplatin and radiotherapy dosage as for CRSC. The primary outcome was overall survival, whereas the secondary outcomes included progression-free survival and toxicity. Results: The median overall survival was 75 months (range 4-86 months) for the CRSC group and 66 months (range 3-87 months) for the CRC group (P = 0.039). The median corresponding progression-free survival was 66 months (range 3-75 months) and 58 months (range 3-71 months), respectively (P = 0.042). The toxicity profile was similar in both the groups. Conclusion: Our results suggested that CRSC might be more effective than CRC in patients with ACC with acceptable toxicity (AU)

No disponible

A phase II study of feasibility and toxicity of bevacizumab in combination with temozolomide in patients with recurrent glioblastoma

Purpose. The aim of this prospective and multicentric phase II study was to evaluate the efficacy and safety of temozolomide (TMZ) and bevacizumab (BV) in patients (pts) with recurrent glioblastoma (GB), previously treated with chemoradiotherapy and at least three cycles of adjuvant TMZ. Patients and methods. Patients with GB at first relapse received BV 10 mg/kg day every 2 weeks and TMZ 150 mg/m2 days 1–7 and 15–21, every 28 days. Patients underwent brain magnetic resonance imaging every 8 weeks. Results. Thirty-two evaluable pts were recruited in 8 sites. Fourteen pts (44 %) had gross total resection. O6-methylguanine-DNA methyltransferase (MGMT) promoter was methylated in 12 pts, unmethylated in 6 pts, and missing in 14 pts. The estimated 6-month progression free survival (PFS) rate was 21.9 % (95 % CI 9.3–40.0 %). The median PFS and overall survival (OS) were 4.2 months (95 % CI 3.6–5.4 months) and 7.3 months (95 % CI 5.8–8.8 months), respectively. No significant association with MGMT status was found in terms of OS or PFS. Six of 32 pts (19 %; 95 % CI 7.2–36.4) were long-term survivors, with a median PFS and OS (50 % events) of 9.5 months (95 % CI 7.9–23.6) and 15.4 (95 % CI 8.9–NA), respectively: no differences in baseline characteristics were identified in comparison with total population. No unexpected toxicities or treatment-related deaths were observed. Conclusions. This regimen showed to be feasible and well tolerated in pts with recurrent GB pretreated with TMZ. Further investigation is warranted to identify subpopulations that are more likely to benefit from addition of BV to GB therapy (AU)

No disponible

Nanoparticle-based brachytherapy spacers for delivery of localized combined chemoradiation therapy.

PURPOSE: In radiation therapy (RT), brachytherapy-inert source spacers are commonly used in clinical practice to achieve high spatial accuracy. These implanted devices are critical technical components of precise radiation delivery but provide no direct therapeutic benefits. METHODS AND MATERIALS: Here we have fabricated implantable nanoplatforms or chemoradiation therapy (INCeRT) spacers loaded with silica nanoparticles (SNPs) conjugated containing a drug, to act as a slow-release drug depot for simultaneous localized chemoradiation therapy. The spacers are made of poly(lactic-co-glycolic) acid (PLGA) as matrix and are physically identical in size to the commercially available brachytherapy spacers (5 mm × 0.8 mm). The silica nanoparticles, 250 nm in diameter, were conjugated with near infrared fluorophore Cy7.5 as a model drug, and the INCeRT spacers were characterized in terms of size, morphology, and composition using different instrumentation techniques. The spacers were further doped with an anticancer drug, docetaxel. We evaluated the in vivo stability, biocompatibility, and biodegradation of these spacers in live mouse tissues. RESULTS: The electron microscopy studies showed that nanoparticles were distributed throughout the spacers. These INCeRT spacers remained stable and can be tracked by the use of optical fluorescence. In vivo optical imaging studies showed a slow diffusion of nanoparticles from the spacer to the adjacent tissue in contrast to the control Cy7.5-PLGA spacer, which showed rapid disintegration in a few days with a burst release of Cy7.5. The docetaxel spacers showed suppression of tumor growth in contrast to control mice over 16 days. CONCLUSIONS: The imaging with the Cy7.5 spacer and therapeutic efficacy with docetaxel spacers supports the hypothesis that INCeRT spacers can be used for delivering the drugs in a slow, sustained manner in conjunction with brachytherapy, in contrast to the rapid clearance of the drugs when administered systemically. The results demonstrate that these spacers with tailored release profiles have potential in improving the combined therapeutic efficacy of chemoradiation therapy.

Technical note: 9-month repositioning accuracy for functional response assessment in head and neck chemoradiotherapy.

The use of thermoplastic immobilisation masks in head and neck radiotherapy is now common practice. The accuracy of these systems has been widely studied, but always within the context and time frame of the radiation delivery-some 6-8 weeks. There is growing current interest in the use of functional imaging to assess the response to treatment, particularly in the head and neck. It is therefore of interest to determine the accuracy with which functional images can be registered to baseline CT over the extended periods of time used for functional response assessment: 3-6 months after radiotherapy. In this study, repeated contrast-enhanced diagnostic quality CT and mid-quality localisation CT from a positron emission tomography/CT scanner were available for five time points over a period of 9 months (before, during and up to 6 months after chemoradiotherapy) for a series of eight patients enrolled in a clinical pilot study. All images were acquired using thermoplastic immobilisation masks. The overall set-up accuracy obtained from this 9-month study of 5.5 ± 3.2 mm (1 standard deviation) and 1.9 ± 1.3° (1 standard deviation) is in agreement with published data acquired over 6-8 weeks. No statistically significant change in set-up error was seen with time. This work indicates that thermoplastic immobilisation masks can be used to accurately align multimodality functional image data for assessment of the response to treatment in head and neck patients over extended follow-up periods.