Malignant melanoma frequently develops cutaneous and/or subcutaneous metastases during the course of the disease. These may present as non-nodal locoregional metastases (microsatellite, satellite, or ...in-transit) included in stage III or as distant metastases in stage IV. Their presentation is heterogeneous and associated with significant morbidity resulting from both disease-related functional damage and treatment side effects. The standard treatment is surgical excision, whereas local therapies or systemic therapies have a role when surgery is not indicated. Radiotherapy can be used in the local management of ITM, subcutaneous relapses, or distant metastases to provide symptom relief and prolong regional disease control. To increase the local response without increasing toxicity, the addition of hyperthermia and intralesional therapies to radiotherapy appear to be very promising. Boron neutron capture therapy, based on nuclear neutron capture and boron isotope fission reaction, could be an alternative to standard treatments, but its use in clinical practice is still limited. The potential benefit of combining radiotherapy with targeted therapies and immunotherapy has yet to be explored in this lesion setting. This review explores the role of radiotherapy in the treatment of cutaneous and subcutaneous lesions, its impact on outcomes, and its association with other treatment modalities.
Introduction
The COVID-19 pandemic has challenged healthcare systems worldwide over the last few months, and it continues to do so. Although some restrictions are being removed, it is not certain ...when the pandemic is going to be definitively over. Pandemics can be seen as a highly complex logistic scenario. From this perspective, some of the indications provided for palliative radiotherapy (PRT) during the COVID-19 pandemic could be maintained in the future in settings that limit the possibility of patients achieving symptom relief by radiotherapy.
This paper has two aims: (1) to provide a summary of the indications for PRT during the COVID-19 pandemic; since some indications can differ slightly, and to avoid any possible contradictions, an expert panel composed of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) and the Palliative Care and Supportive Therapies Working Group (AIRO-palliative) voted by consensus on the summary; (2) to introduce a clinical care model for PRT endorsed by AIRO and by a spontaneous Italian collaborative network for PRT named “La Rete del Sollievo” (“The Net of Relief”). The proposed model, denoted “No cOmpRoMise on quality of life by pALliative radiotherapy” (NORMALITY), is based on an AIRO-palliative consensus-based list of clinical indications for PRT and on practical suggestions regarding the management of patients potentially suitable for PRT but dealing with highly complex logistics scenarios (similar to the ongoing logistics limits due to COVID-19).
Material and Methods
First, a summary of the available literature guidelines for PRT published during the COVID-19 pandemic was prepared. A systematic literature search based on the PRISMA approach was performed to retrieve the available literature reporting guideline indications fully or partially focused on PRT. Tables reporting each addressed clinical presentation and respective literature indications were prepared and distributed into two main groups: palliative emergencies and palliative non-emergencies. These summaries were voted in by consensus by selected members of the AIRO and AIRO-palliative panels. Second, based on the summary for palliative indications during the COVID-19 pandemic, a clinical care model to facilitate recruitment and delivery of PRT to patients in complex logistic scenarios was proposed. The summary tables were critically integrated and shuffled according to clinical presentations and then voted on in a second consensus round. Along with the adapted guideline indications, some methods of performing the first triage of patients and facilitating a teleconsultation preliminary to the first in-person visit were developed.
Results
After the revision of 161 documents, 13 papers were selected for analysis. From the papers, 19 clinical presentation items were collected; in total, 61 question items were extracted and voted on (i.e., for each presentation, more than one indication was provided from the literature). Two tables summarizing the PRT indications during the COVID-19 pandemic available from the literature (PRT COVID-19 summary tables) were developed: palliative emergencies and palliative non-emergencies. The consensus of the vote by the AIRO panel for the PRT COVID-19 summary was reached. The PRT COVID-19 summary tables for palliative emergencies and palliative non-emergencies were adapted for clinical presentations possibly associated with patients in complex clinical scenarios other than the COVID-19 pandemic. The two new indication tables (i.e., “Normality model of PRT indications”) for both palliative emergencies and palliative non-emergencies were voted on in a second consensus round. The consensus rate was reached and strong. Written forms facilitating two levels of teleconsultation (triage and remote visits) were also developed, both in English and in Italian, to evaluate the patients for possible indications for PRT before scheduling clinical visits.
Conclusion
We provide a comprehensive summary of the literature guideline indications for PRT during COVID-19 pandemic. We also propose a clinical care model including clinical indications and written forms facilitating two levels of teleconsultation (triage and remote visits) to evaluate the patients for indications of PRT before scheduling clinical visits. The normality model could facilitate the provision of PRT to patients in future complex logistic scenarios.
Cancer radiotherapy (RT) may induce what is referred to as the "abscopal effect," a regression of non-irradiated metastatic lesions distant from the primary tumor site directly subject to ...irradiation. This clinical response is rare, but has been surmised to be an immune-mediated phenomenon, suggesting that immunotherapy and RT could potentially synergize. Here, we report the outcome of patients with advanced melanoma treated with the immune checkpoint blockade monoclonal antibody antagonist, ipilimumab followed by RT. Patients were selected for enrollment at the National Cancer Institute "Fondazione G.Pascale" through the expanded access program in Italy. Those who experienced disease progression after ipilimumab thus received subsequent RT and were selected for analysis. Among 21 patients, 13 patients (62%) received RT to treat metastases in the brain and 8 received RT directed at extracranial sites. An abscopal response was observed in 11 patients (52%), 9 of whom had partial responses (43%) and 2 had stable disease (10%). The median time from RT to an abscopal response was 1 month (range 1-4). Median overall survival (OS) for all 21 patients was 13 months (range 6-26). Median OS for patients with abscopal responses was extended to 22.4 months (range 2.5-50.3) vs. 8.3 months (range 7.6-9.0) without. A local response to RT was detected in 13 patients (62%) and, of these, 11 patients (85%) had an abscopal response and abscopal effects were only observed among patients exhibiting a local response. These results suggest RT after ipilimumab may lead to abscopal responses in some patients with advanced melanoma correlating with prolonged OS. Our data also suggest that local responses to RT may be predictive of abscopal responses. Further research in larger randomized trials is needed to validate these results.
Hypofractionation for localized prostate cancer treatment is rapidly spreading in the medical community and it is supported by radiobiological evidences (lower α/β 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 ± 0.5% HT. P < .05) and good sparing of OARs. Nevertheless, the beam-on time showed a significant difference (37 ± 9 m CK; 7.1 ± 0.3 m VMAT; 17 ± 2 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.
Introduction
The prognosis of glioma is dismal, and almost all patients relapsed. At recurrence time, several treatment options are considered, but to date there is no a standard of care. The ...Neurooncology Study Group of the Italian Association of Radiation Oncology (AIRO) collected clinical data regarding a large series of recurrent glioma patients who underwent re-irradiation (re-RT) in Italy.
Methods
Data regarding 300 recurrent glioma patients treated from May 2002 to November 2017, were analyzed. All patients underwent re-RT. Surgical resection, followed by re-RT with concomitant and adjuvant chemotherapy was performed. Clinical outcome was evaluated by neurological examination and brain MRI performed, 1 month after radiation therapy and then every 3 months.
Results
Re-irradiation was performed at a median interval time (IT) of 16 months from the first RT. Surgical resection before re-RT was performed in 19% of patients, concomitant temozolomide (TMZ) in 16.3%, and maintenance chemotherapy in 29%. Total doses ranged from 9 Gy to 52.5 Gy, with a median biological effective dose of 43 Gy. The median, 1, 2 year OS were 9.7 months, 41% and 17.7%. Low grade glioma histology (p ≪ 0.01), IT > 12 months (p = 0.001), KPS > 70 (p = 0.004), younger age (p = 0.001), high total doses delivered (p = 0.04), and combined treatment performed (p = 0.0008) were recorded as conditioning survival.
Conclusion
our data underline re-RT as a safe and feasible treatment with limited rate of toxicity, and a combined ones as a better option for selected patients. The identification of a BED threshold able to obtain a greater benefit on OS, can help in designing future prospective studies.
Cholangiocarcinoma (CCA) is a rare cancer originating from the biliary epithelium and accounts for about 3% of all gastrointestinal malignancies. Unfortunately, the majority of patients are not ...eligible for surgical resection at the time of diagnosis, because of the locally advanced stage or metastatic disease. The overall survival time of unresectable CCA is generally less than 1 year, despite current chemotherapy regimens. Biliary drainage is often required as a palliative treatment for patients with unresectable CCA. Recurrent jaundice and cholangitis tend to occur because of reobstruction of the biliary stents. This not only jeopardizes the efficacy of chemotherapy, but also causes significant morbidity and mortality. Effective control of tumor growth is crucial for prolonging stent patency and consequently patient survival. Recently, endobiliary radiofrequency ablation (ERFA) has been experimented as a treatment modality to reduce tumor mass, and delay tumor growth, extending stent patency. Ablation is accomplished by means of high-frequency alternating current which is released from the active electrode of an endobiliary probe placed in a biliary stricture. It has been shown that tumor necrosis releases intracellular particles which are highly immunogenic and activate antigen-presenting cells, enhancing local immunity directed against the tumor. This immunogenic response could potentially enhance tumor suppression and be responsible for improved survival of patients with unresectable CCA who undergo ERFA. Several studies have demonstrated that ERFA is associated with an increased median survival of approximately 6 months in patients with unresectable CCA. Furthermore, recent data support the hypothesis that ERFA could ameliorate the efficacy of chemotherapy administered to patients with unresectable CCA, without increasing the risk of complications. This narrative review discusses the results of the studies published in recent years and focuses on the impact that ERFA could have on overall survival of patients with unresectable cholangiocarcinoma.
The clinical observation showed a potential additive effect of anti-PD-1 agents and cetirizine in patients with advanced melanoma.
Clinical outcomes of concomitant cetirizine/anti-PD-1 treatment of ...patients with stage IIIb-IV melanoma were retrospectively collected, and a transcriptomic analysis was performed on blood samples obtained at baseline and after 3 months of treatment.
Patients treated with cetirizine concomitantly with an anti-PD-1 agent had significantly longer progression-free survival (PFS; mean PFS: 28 vs 15 months, HR 0.46, 95% CI: 0.28-0.76; p = 0.0023) and OS (mean OS was 36 vs 23 months, HR 0.48, 95% CI: 0.29-0.78; p = 0.0032) in comparison with those not receiving cetirizine. The concomitant treatment was significantly associated with ORR and DCR (p < 0.05). The expression of FCGR1A/CD64, a specific marker of macrophages, was increased after the treatment in comparison with baseline in blood samples from patients receiving cetirizine, but not in those receiving only the anti-PD1, and positively correlated with the expression of genes linked to the interferon pathway such as CCL8 (rho = 0.32; p = 0.0111), IFIT1 (rho = 0.29; p = 0.0229), IFIT3 (rho = 0.57; p < 0.0001), IFI27 (rho = 0.42; p = 0.008), MX1 (rho = 0.26; p = 0.0383) and RSAD2 (rho = 0.43; p = 0.0005).
This retrospective study suggests that M1 macrophage polarization may be induced by cetirizine through the interferon-gamma pathway. This effect may synergize with the immunotherapy of advanced melanoma with anti-PD-1 agents.
Simple summary
Stereotactic body radiotherapy (SBRT) of 35–36.25 Gy in five fractions with the CyberKnife System yields excellent control with low toxicity in low–intermediate-risk prostate cancer ...patients. We found no differences in biochemical control and overall survival in relation to dose. There were no significant differences in toxicity or quality of life between the two groups.
Aims
Stereotactic body radiotherapy (SBRT) is an emerging therapeutic approach for low- and intermediate-risk prostate cancer. We present retrospective data on biochemical control, toxicity, and quality of life of CyPro Trial.
Materials and methods
A total of 122 patients with low- and intermediate-risk prostate cancer were treated with the CyberKnife System at a dose of 35 Gy or 36.25 Gy in five fractions. Biochemical failure (BF)/biochemical disease-free survival (bDFS) was defined using the Phoenix method (nadir + 2 ng/ml). Acute/late rectal and urinary toxicities were assessed by the Radiation Therapy Oncology Group (RTOG) toxicity scale. Quality of life (QoL) was assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ C30 and PR25. International Erectile Function Index-5 (IIEF5) and International Prostate Symptom Score (IPSS) questionnaires were administered at baseline, every 3 months after treatment during the first years, and then at 24 months and 36 months.
Results
The 1-, 2-, and 5-year DFS rates were 92.9%, 92.9%, and 92.3%, respectively, while the 1-, 2-, and 5-year bDFS rates were 100%, 100%, and 95.7%, respectively. With regard to risk groups or doses, no statistically significant differences were found in terms of DFS or bDFS. Grade 2 urinary toxicity was acute in 10% and delayed in 2% of patients. No Grade 3 acute and late urinary toxicity was observed. Grade 2 rectal toxicity was acute in 8% and late in 1% of patients. No Grade 3–4 acute and late rectal toxicity was observed. Grade 2 acute toxicity appeared higher in the high-dose group (20% in the 36.25-Gy group versus 3% in the 35-Gy group) but was not statistically significant.
Conclusion
Our study confirms that SBRT of 35–36.25 Gy in five fractions with the CyberKnife System produces excellent control with low toxicity in patients with low–intermediate-risk prostate cancer. We found no dose-related differences in biochemical control and overall survival. Further confirmation of these results is awaited through the prospective phase of this study, which is still ongoing.
Background Metastatic disease in tumors originating from the gastrointestinal tract can exhibit varying degrees of tumor burden at presentation. Some patients follow a less aggressive disease course, ...characterized by a limited number of metastatic sites, referred to as "oligo-metastatic disease" (OMD). The precise biological characteristics that define the oligometastatic behavior remain uncertain. In this study, we present a protocol designed to prospectively identify OMD, with the aim of proposing novel therapeutic approaches and monitoring strategies. Methods The PREDICTION study is a monocentric, prospective, observational investigation. Enrolled patients will receive standard treatment, while translational activities will involve analysis of the tumor microenvironment and genomic profiling using immunohistochemistry and next-generation sequencing, respectively. The first primary objective (descriptive) is to determine the prevalence of biological characteristics in OMD derived from gastrointestinal tract neoplasms, including high genetic concordance between primary tumors and metastases, a significant infiltration of T lymphocytes, and the absence of clonal evolution favoring specific driver genes (KRAS and PIK3CA). The second co-primary objective (analytic) is to identify a prognostic score for true OMD, with a primary focus on metastatic colorectal cancer. The score will comprise genetic concordance (> 80%), high T-lymphocyte infiltration, and the absence of clonal evolution favoring driver genes. It is hypothesized that patients with true OMD (score 3+) will have a lower rate of progression/recurrence within one year (20%) compared to those with false OMD (80%). The endpoint of the co-primary objective is the rate of recurrence/progression at one year. Considering a reasonable probability (60%) of the three factors occurring simultaneously in true OMD (score 3+), using a significance level of alpha = 0.05 and a test power of 90%, the study requires a minimum enrollment of 32 patients. Discussion Few studies have explored the precise genetic and biological features of OMD thus far. In clinical settings, the diagnosis of OMD is typically made retrospectively, as some patients who undergo intensive treatment for oligometastases develop polymetastatic diseases within a year, while others do not experience disease progression (true OMD). In the coming years, the identification of true OMD will allow us to employ more personalized and comprehensive strategies in cancer treatment. Trial registration ClinicalTrials.gov ID NCT05806151. Keywords: Oligometastatic diseases, Colorectal cancer, Biomarkers, Genetics, Prognosis
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background Prostate cancer (PCa) is the second most common cancer in men worldwide. The standard non-surgical approach for localized PCa is radiotherapy (RT), but one of the limitations of high-dose ...RT is the potential increase in gastrointestinal and genitourinary toxicities. We present the protocol of the Microstyle study, a multicentre randomized two-arm crossover clinical trial. The primary outcome will be assessed at the end of 6-month intervention, by measuring the change in adherence to a healthy lifestyle score. The hypothesis is that modifying lifestyle we change microbiome and improve quality of life and decrease side effects of RT. Methods Study participants will be recruited among men undergoing RT in two Italian centers (Milan and Naples). We foresee to randomize 300 patients in two intervention arms: Intervention Group (IG) and Control Group (CG). Participants allocated to the IG will meet a dietitian and a physiotherapist before RT to receive personalized diet and exercise recommendations, according to their health status, to improve overall lifestyle and reduce side effects (bowel and/or urinary problems). Dietitian and physiotherapist will work together to set individualized goals to reduce or eliminate side effects and pain according to their health status. All participants (IG) will be given a pedometer device (steps counter) in order to monitor and to spur participants to increase physical activity and reduce sedentary behavior. Participants included in the CG will receive baseline general advice and materials available for patients undergoing RT. According to the cross-over design, the CG will cross to the intervention approach after 6-month, to actively enhance compliance towards suggested lifestyle recommendations for all patients. Discussion This trial is innovative in its design because we propose a lifestyle intervention during RT, that includes both dietary and physical activity counselling, as well as monitoring changes in microbiome and serum biomarkers. The promotion of healthy behaviour will be initiated before initiation of standard care, to achieve long lasting effects, controlling side effects, coping with feelings of anxiety and depression and improve efficacy of RT. Trial registration ClincalTrial.gov registration number: NCT05155618. Retrospectively registered on December 13, 2021. The first patient was enrolled on October 22, 2021. Keywords: Prostate cancer, Randomized controlled trial, Diet, Physical activity, Counseling, Quality of life, Body composition, Microbiome, Serum biomarkers, Radiotherapy
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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