Abstract Purpose Although radical cystectomy is still considered the standard of care for most localized muscle-invasive bladder cancer (MIBC) patients, bladder-sparing strategies with ...chemoradiotherapy have demonstrated comparable local control and survival rates when adjusting for tumor stage. We present a pooled analysis of individual patient data out of published trials with gemcitabine-based chemoradiotherapy for MIBC. Methods and materials Individual patient data were collected from Institutions that enrolled patients into trials that evaluated gemcitabine-based chemoradiotherapy for MIBC. Results We identified eight studies published on gemcitabine-based radiochemotherapy and 190 patients were included in this analysis. A complete response (CR) was observed in 166 patients (93%). After a median follow up of 44.5 months, 36 patients (18.9%) presented a bladder recurrence and 14 subsequently underwent cystectomy. The 5-year overall survival (OS), disease-specific survival (DSS), and cystectomy-free survival (CFS) rates were 59%, 80.9%, and 93.3%, respectively. The achievement of CR after chemoradiotherapy was the main prognostic variable which was associated with improved OS, DSS, and CFS. The treatment was well tolerated. Conclusion This pooled analysis strengthens the evidence that chemoradiotherapy regimens with concurrent gemcitabine are feasible and well tolerated. Prospective randomized controlled trials are on-going to definitively assess the efficacy of gemcitabine-based chemoradiotherapy for MIBC.
•Ablative radiotherapy is an effective treatment for oligometastatic prostate cancer.•The lack of randomized phase III trials hampers the generalization of this therapy.•In clinical practice, ...ablative radiotherapy should be adopted in some cases only.•This position paper explores available literature and proposes some recommendations.
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.
AIMS
Intravesical instillation of hyaluronic acid (HA) plus chondroitin sulfate (CS) in women with bladder pain syndrome/interstitial cystitis (BPS/IC) has shown promising results. This study ...compared the efficacy, safety, and costs of intravesical HA/CS (Ialuril®, IBSA) to dimethyl sulfoxide (DMSO).
METHODS
Randomized, open‐label, multicenter study involving 110 women with BPS/IC. The allocation ratio (HA/CS:DMSO) was 2:1. Thirteen weekly instillations of HA (1.6%)/CS (2.0%) or 50% DMSO were given. Patients were evaluated at 3 (end‐of‐treatment) and 6 months. Primary endpoint was reduction in pain intensity at 6 months by visual analogue scale (VAS) versus baseline. Secondary efficacy measurements were quality of life and economic analyses.
RESULTS
A significant reduction in pain intensity was observed at 6 months in both treatment groups versus baseline (P < 0.0001) in the intention‐to‐treat population. Treatment with HA/CS resulted in a greater reduction in pain intensity at 6 months compared with DMSO for the per‐protocol population (mean VAS reduction 44.77 ± 25.07 vs. 28.89 ± 31.14, respectively; P = 0.0186). There were no significant differences between treatment groups in secondary outcomes. At least one adverse event was reported in 14.86% and 30.56% of patients in the HA/CS and DMSO groups, respectively. There were significantly fewer treatment‐related adverse events for HA/CS versus DMSO (1.35% vs. 22.22%; P = 0.001). Considering direct healthcare costs, the incremental cost‐effectiveness ratio of HA/CS versus DMSO fell between 3735€/quality‐adjusted life years (QALY) and 8003€/QALY.
CONCLUSIONS
Treatment with HA/CS appears to be as effective as DMSO with a potentially more favorable safety profile. Both treatments increased health‐related quality of life, while HA/CS showed a more acceptable cost‐effectiveness profile.
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•A systematic review of studies comparing TMT and RC for MIBC patients was performed.•Qualitative and quantitative evaluation of outcomes was performed with GRADE system.•A final weak ...positive recommendation in favour of TMT versus RC was developed.
To compare trimodality therapy (TMT) versus radical cystectomy (RC) and develop GRADE (Grades of Recommendation, Assessment, Development and Evaluation) Recommendation by the Italian Association of Radiotherapy and Clinical Oncology (AIRO) for treatment of muscle-invasive bladder cancer (MIBC).
Prospective and retrospective studies comparing TMT and RC for MIBC patients were included. Qualitative and quantitative evaluation of evidence was made.
Ten studies were included in the analysis. Pooled analysis showed salvage cystectomy and pathological complete response rates after TMT of 12 % and 72–77.5 %, respectively. Pooled rates of G3-G4 GU toxicity and serious toxicity rate were 18 vs 3% and 45 vs 29 % for patients undergoing TMT vs RC, respectively. The panel assessed a substantial equivalence in terms of OS and CSS at 5 years between TMT and RC.
TMT could be suggested as an alternative treatment to RC in non-metastatic MIBC patients, deemed fit for surgery.
Conventional pharmacological therapies for the treatment of juvenile idiopathic arthritis (JIA) consist of non-biological, disease-modifying antirheumatic drugs, among which methotrexate (MTX) is the ...most commonly prescribed. However, there is a lack of consensus-based clinical and therapeutic recommendations for the use of MTX in the management of patients with JIA. Therefore, the Methotrexate Advice and RecommendAtions on Juvenile Idiopathic Arthritis (MARAJIA) Expert Meeting was convened to develop evidence-based recommendations for the use of MTX in the treatment of JIA.
The preliminary executive committee identified a total of 9 key clinical issues according to the population, intervention, comparator, outcome (PICO) approach, and performed an evidence-based, systematic, literature review. During the subsequent Expert Meeting, the relevant evidence was assessed and graded, and 10 recommendations were made.
Recommendations relating to the efficacy, optimal dosing and route of administration and duration of treatment with MTX in JIA, and to the issue of folic acid supplementation to prevent MTX side effects, use of MTX in the treatment of chronic JIA-associated uveitis, combination treatment with biologic agents, and the use of vaccinations in patients with JIA were developed. The selected topics were considered to represent clinically important issues facing clinicians caring for patients with JIA. Evidence was insufficient to formulate recommendations for the use of biomarkers predictive of treatment response.
These consensus recommendations provide balanced and evidence-based recommendations designed to have broad value for physicians and healthcare clinicians involved in the clinical management of patients with JIA.
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).
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.
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.
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.
•The prognostic impact of pCR after primary systemic therapy on DFS and OS has been shown in meta-analyses of randomized phase III trials.•The association of treatment response with loco-regional recurrence has been studied only in retrospective reports.•RNI should be strongly considered in patients with clinically involved lymph nodes regardless of the response to primary systemic therapy, especially in the presence of further risk factors.•In patients with cN2 at diagnosis and ypN0 at surgery after PST, loco-regional RT should be evaluated for each patient in the multidisciplinary team.
Despite three-weekly cisplatin chemoradiotherapy is considered the standard treatment, the optimal cisplatin-based regimen in head and neck cancer is still debated.
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•The optimal ...cisplatin-based regimen in head and neck cancer is still debated.•Three-weekly cisplatin chemoradiotherapy is considered the standard treatment.•Weekly cisplatin chemoradiotherapy is a valid option.•This analysis provides reasonable clinical recommendations based on GRADE system.
To evaluate efficacy and toxicity of weekly cisplatin chemoradiotherapy versus three-weekly cisplatin chemoradiotherapy and identify differences in clinical outcomes and severe toxicity rate.
PICOS/PRISMA methods were used to identify studies on PubMed, EMBASE and Cochrane Library, 2005–2019.
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.
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.
In the past decade, nine antibody-drug conjugates (ADCs) have been approved for the treatment of various tumors, four of which specifically for solid malignancies. ADCs deliver the cytotoxic payload ...to the cancer site, thereby improving chemotherapy efficacy while reducing systemic drug exposure and toxicity. With their high selectivity, ADCs are associated with a manageable side-effect profile, with nausea and vomiting being among the most frequent toxicities, although this may vary according to the respective ADC and the associated payload. Information about the emetic risk of the new ADC compounds is limited. Three virtual focus groups of Italian oncologists were held to raise awareness on the importance of an antiemetic prophylaxis regimen to prevent and mitigate ADC-associated emesis and its sequelae. After reviewing published evidence and guidelines, the three expert panels shared their experience on the early use of ADCs gained through the participation in specific clinical trials and their clinical practice. The following issues were discussed: antiemetic therapy during trastuzumab deruxtecan treatment, with a protocol adopted at the San Raffaele Hospital (Milan, Italy); the use of steroids; the management of anticipatory nausea during trastuzumab deruxtecan therapy; nutritional counselling; and effective doctor-patient communication. The experts acknowledged that recommendations should be drug-specific, and formulated opinion-based advice intended to guide physicians in their daily practice until further evidence emerges.
Many treatment approaches are now available for neuroendocrine neoplasms (NENs). While several societies have issued guidelines for diagnosis and treatment of NENs, there are still areas of ...controversy for which there is limited guidance. Expert opinion can thus be of support where firm recommendations are lacking. A group of experts met to formulate 14 statements relative to diagnosis and treatment of NENs and presented herein. The nominal group and estimate-talk-estimate techniques were used. The statements covered a broad range of topics from tools for diagnosis to follow-up, evaluation of response, treatment efficacy, therapeutic sequence, and watchful waiting. Initial prognostic characterization should be based on clinical information as well as histopathological analysis and morphological and functional imaging. It is also crucial to optimize RLT for patients with a NEN starting from accurate characterization of the patient and disease. Follow-up should be patient/tumor tailored with a shared plan about timing and type of imaging procedures to use to avoid safety issues. It is also stressed that patient-reported outcomes should receive greater attention, and that a multidisciplinary approach should be mandatory. Due to the clinical heterogeneity and relative lack of definitive evidence for NENs, personalization of diagnostic-therapeutic work-up is crucial.
Introduction
Almost 30% of non-small cell lung cancer (NSCLC) patients have locally advanced-stage disease. In this setting, definitive radiotherapy concurrent to chemotherapy plus adjuvant ...immunotherapy (cCRT + IO) is the standard of care, although only 40% of these patients are eligible for this approach.
Aims
A comparison between cCRT and hypofractionated radiotherapy regimens (hypo-fx RT) with the addition of sequential chemotherapy (sCHT) could be useful for future combinations with immunotherapy. We developed a recommendation about the clinical question of whether CHT and moderately hypo-fx RT are comparable to cCRT for locally advanced NSCLC
Materials and methods
The panel used GRADE methodology and the Evidence to Decision (EtD) framework. After a systematic literature search, five studies were eligible. We identified the following outcomes: progression-free survival (PFS), overall survival (OS), freedom from locoregional recurrence (FFLR), deterioration of quality of life (QoL), treatment-related deaths, severe G3–G4 toxicity, late pulmonary toxicity G3–G4, and acute esophageal toxicity G3–G4.
Results
The probability of OS and G3–G4 late lung toxicity seems to be worse in patients submitted to sCHT and hypo-fx RT. The panel judged unfavorable the balance benefits/harms.
Conclusions
The final recommendation was that sCHT followed by moderately hypo-fx RT should not be considered as an alternative to cCRT in unresectable stage III NSCLC patients.
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