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BACKGROUND: Comprehensive next-generation sequencing is widely used for precision oncology and precision prevention approaches. We aimed to determine the yield of actionable gene variants, the capacity to uncover hereditary predisposition and liquid biopsy appropriateness instead of, or in addition to, tumor tissue analysis, in a real-world cohort of cancer patients, who may benefit the most from comprehensive genomic profiling. METHODS: Seventy-eight matched germline/tumor tissue/liquid biopsy DNA and RNA samples were profiled using the Hereditary Cancer Panel (germline) and the TruSight Oncology 500 panel (tumor tissue/cfDNA) from 23 patients consecutively enrolled at our center according to at least one of the following criteria: no available therapeutic options; long responding patients potentially fit for other therapies; rare tumor; suspected hereditary cancer; primary cancer with high metastatic potential; tumor of unknown primary origin. Variants were annotated for OncoKB and AMP/ASCO/CAP classification. RESULTS: The overall yield of actionable somatic and germline variants was 57% (13/23 patients), and 43.5%, excluding variants previously identified by somatic or germline routine testing. The accuracy of tumor/cfDNA germline-focused analysis was demonstrated by overlapping results of germline testing. Five germline variants in BRCA1, VHL, CHEK1, ATM genes would have been missed without extended genomic profiling. A previously undetected BRAF p.V600E mutation was emblematic of the clinical utility of this approach in a patient with a liver undifferentiated embryonal sarcoma responsive to BRAF/MEK inhibition. CONCLUSIONS: Our study confirms the clinical relevance of performing extended parallel tumor DNA and cfDNA testing to broaden therapeutic options, to longitudinally monitor cfDNA during patient treatment, and to uncover possible hereditary predisposition following tumor sequencing in patient care.
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Genômica , Mutação em Linhagem Germinativa , Neoplasias , Humanos , Feminino , Biópsia Líquida , Neoplasias/genética , Neoplasias/patologia , Masculino , Pessoa de Meia-Idade , Estudos de Coortes , Mutação em Linhagem Germinativa/genética , Genômica/métodos , Adulto , Idoso , Células Germinativas/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Predisposição Genética para DoençaRESUMO
Cutaneous squamous cell carcinoma (CSCC) accounts for â¼20%-25% of all skin tumors. Its precise incidence is often challenging to determine due to limited statistics and its incorporation with mucosal forms. While most cases have a favorable prognosis, challenges arise in patients presenting with locally advanced or metastatic forms, mainly appearing in immunocompromised patients, solid organ transplantation recipients, or those facing social difficulties. Traditionally, chemotherapy and targeted therapy were the mainstays for advanced cases, but recent approvals of immunotherapeutic agents like cemiplimab and pembrolizumab have revolutionized treatment options. These guidelines, developed by the Italian Association of Medical Oncologists (AIOM) using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach, aim to guide clinicians in diagnosing, treating, and monitoring patients with CSCC, covering key aspects from primitive tumors to advanced stages, selected by a panel of experts selected by AIOM and other national scientific societies. The incorporation of these guidelines into clinical practice is expected to enhance patient care and address the evolving landscape of CSCC management.
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Carcinoma de Células Escamosas , Oncologia , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/terapia , Neoplasias Cutâneas/diagnóstico , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/diagnóstico , Itália , Oncologia/normas , Guias de Prática Clínica como AssuntoRESUMO
Basal cell carcinoma (BCC) is the most common form of cancer, with a high impact on the public health burden and social costs. Despite the overall prognosis for patients with BCC being excellent, if lesions are allowed to progress, or in a small subset of cases harboring an intrinsically aggressive biological behavior, it can result in local spread and significant morbidity, and conventional treatments (surgery and radiotherapy) may be challenging. When a BCC is not amenable to either surgery or radiotherapy with a reasonable curative intent, or when metastatic spread occurs, systemic treatments with Hedgehog inhibitors are available. These guidelines were developed, applying the GRADE approach, on behalf of the Italian Association of Medical Oncologists (AIOM) to assist clinicians in treating patients with BCC. They contain recommendations with regard to the diagnosis, treatment and follow-up, from primitive tumors to those locally advanced or metastatic, addressing the aspects of BCC management considered as priorities by a panel of experts selected by AIOM and other national scientific societies. The use of these guidelines in everyday clinical practice should improve patient care.
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Carcinoma Basocelular , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/terapia , Neoplasias Cutâneas/tratamento farmacológico , Abordagem GRADE , Proteínas Hedgehog/uso terapêutico , Carcinoma Basocelular/terapia , Carcinoma Basocelular/tratamento farmacológico , Oncologia , Itália/epidemiologiaRESUMO
BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the management of multiple tumors, due to improved efficacy, quality of life, and safety. While most immune-related adverse events (irAEs) are mild and easily managed, in rare cases such events may be life-threatening, especially those affecting the neuromuscular and cardiac system. The management of neuromuscular/cardiac irAEs is not clear due to the lack of consistent data. Therefore, we carried out a pooled analysis of collected cases from selected Italian centers and individual data from published case reports and case series, in order to improve our understanding of these irAEs. PATIENTS AND METHODS: We collected retrospective data from patients treated in six Italian centers with ICIs (programmed cell death protein 1 or programmed death-ligand 1 and/or cytotoxic T-lymphocyte antigen 4 inhibitor) for any solid tumor who experienced neuromuscular and/or cardiovascular toxicity. Then, we carried out a search of case reports and series of neuromuscular/cardiac irAEs from ICIs with any solid tumor. RESULTS: This analysis includes cases from Italian institutions (n = 18) and the case reports identified in our systematic literature search (n = 120), for a total of 138 patients. Among these patients, 50 (36.2%) had complete resolution of their neuromuscular/cardiac irAEs, in 21 (15.2%) cases there was a clinical improvement with mild sequelae, and 53 (38.4%) patients died as a result of the irAEs. Factors significantly associated with worse outcomes were early irAE onset, within the first two cycles of ICI (Fisher P < 0.0001), clinical manifestation of both myositis and myocarditis when compared with patients who developed only myositis or myocarditis (chi-square P = 0.0045), and the development of arrhythmia (Fisher P = 0.0070). CONCLUSIONS: To the best of our knowledge, this is the largest collection of individual cases of immune-related myocarditis/myositis. Early irAE onset, concurrent development of myositis and myocarditis, as well as occurrence of arrhythmias are associated with worse outcomes and should encourage an aggressive immunomodulatory treatment.
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Antineoplásicos Imunológicos , Miocardite , Miosite , Neoplasias , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Estudos Retrospectivos , Miocardite/induzido quimicamente , Miocardite/tratamento farmacológico , Qualidade de Vida , Neoplasias/tratamento farmacológico , Miosite/induzido quimicamente , Miosite/tratamento farmacológicoRESUMO
Background: Despite having revolutionized the treatment paradigm for advanced melanoma, not all patients benefit from immune checkpoint inhibitor therapy. To date, there are no predictive biomarkers for response or the occurrence of immune-related adverse events (irAEs) to programmed cell death protein 1 (PD-1) inhibitors. Our aim was to investigate the predictive and prognostic role of single nucleotide variants (SNVs) of genes involved in the PD-1 axis. Methods: We analysed, in metastatic melanoma patients treated with nivolumab or pembrolizumab, five PD-1 SNVs, namely PD1.3 G>A (rs11568821), PD1.5 C>T (rs2227981), PD1.6 G>A (rs10204525), PD1.7 T>C(rs7421861), PD1.10 C>G (rs5582977) and three programmed death-ligand 1 (PD-L1) SNVs: +8293 C>A (rs2890658), PD-L1 C>T (rs2297136) and PD-L1 G>C (rs4143815). Association of SNV genotypic frequencies with best overall response to PD-1 inhibitors and development of irAEs were estimated through a modified Poisson regression. A Cox regression modelling approach was applied to evaluate the SNV association with OS. Results: A total of 125 patients with advanced melanoma were included in the analysis. A reduction in irAEs risk was observed in patients carrying the PD-L1 +8293 C/A genotype compared with those carrying the C/C genotype (risk ratio = 0.45; 95% CL 0.22-0.93; P = 0.031). A trend for a reduction in irAEs was also observed with the PD1.5 T allele (risk ratio = 0.70, 95% confidence limits 0.48-1.01 versus C allele). None of the SNVs was associated with response to therapy. Finally, a survival benefit was observed in patients harbouring the PD1.7 C/C genotype (hazard ratio = 0.37; 95% confidence limits 0.14-0.96; P = 0.028) in the homozygous model. Conclusions: Our study showed that PD-1.5 and PD-L1 +8293 SNVs may play a role as a predictive biomarker of development of irAEs to PD-1 inhibitors. PD1.7 SNV may also be associated with a reduction of the risk of death, although further translational research is needed to confirm these results.
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BACKGROUND: The incidence of cutaneous melanoma is increasing in Italy, in parallel with the implementation of gene panels. Therefore, a revision of national genetic assessment criteria for hereditary melanoma may be needed. The aim of this study was to identify predictors of susceptibility variants in the largest prospective cohort of Italian high-risk melanoma cases studied to date. MATERIALS AND METHODS: From 25 Italian centers, we recruited 1044 family members and germline sequenced 940 cutaneous melanoma index cases through a shared gene panel, which included the following genes: CDKN2A, CDK4, BAP1, POT1, ACD, TERF2IP, MITF and ATM. We assessed detection rate according to familial status, region of origin, number of melanomas and presence and type of non-melanoma tumors. RESULTS: The overall detection rate was 9.47% (5.53% analyzing CDKN2A alone), ranging from 5.14% in sporadic multiple melanoma cases (spoMPM) with two cutaneous melanomas to 13.9% in familial cases with at least three affected members. Three or more cutaneous melanomas in spoMPM cases, pancreatic cancer and region of origin predicted germline status [odds ratio (OR) = 3.23, 3.15, 2.43, P < 0.05]. Conversely, age > 60 years was a negative independent predictor (OR = 0.13, P = 0.008), and was the age category with the lowest detection rate, especially for CDKN2A. Detection rate was 19% when cutaneous melanoma and pancreatic cancer clustered together. CONCLUSIONS: Gene panel doubled the detection rate given by CDKN2A alone. National genetic testing criteria may need a revision, especially regarding age cut-off (60) in the absence of strong family history, pancreatic cancer and/or a high number of cutaneous melanomas.
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Melanoma , Neoplasias Pancreáticas , Neoplasias Cutâneas , Inibidor p16 de Quinase Dependente de Ciclina , Mutação em Linhagem Germinativa , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Melanoma Maligno Cutâneo , Neoplasias PancreáticasRESUMO
STUDY QUESTION: Is it safe to perform controlled ovarian stimulation (COS) for fertility preservation before starting anticancer therapies or ART after treatments in young breast cancer patients? SUMMARY ANSWER: Performing COS before, or ART following anticancer treatment in young women with breast cancer does not seem to be associated with detrimental prognostic effect in terms of breast cancer recurrence, mortality or event-free survival (EFS). WHAT IS KNOWN ALREADY: COS for oocyte/embryo cryopreservation before starting chemotherapy is standard of care for young women with breast cancer wishing to preserve fertility. However, some oncologists remain concerned on the safety of COS, particularly in patients with hormone-sensitive tumors, even when associated with aromatase inhibitors. Moreover, limited evidence exists on the safety of ART in breast cancer survivors for achieving pregnancy after the completion of anticancer treatments. STUDY DESIGN, SIZE, DURATION: The present systematic review and meta-analysis was carried out by three blinded investigators using the keywords 'breast cancer' and 'fertility preservation'; keywords were combined with Boolean operators. Eligible studies were identified by a systematic literature search of Medline, Web of Science, Embase and Cochrane library with no language or date restriction up to 30 June 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: To be included in this meta-analysis, eligible studies had to be case-control or cohort studies comparing survival outcomes of women who underwent COS or ART before or after breast cancer treatments compared to breast cancer patients not exposed to these strategies. Survival outcomes of interest were cancer recurrence rate, relapse rate, overall survival and number of deaths. Adjusted relative risk (RR) and hazard ratio (HR) with 95% CI were extracted. When the number of events for each group were available but the above measures were not reported, HRs were estimated using the Watkins and Bennett method. We excluded case reports or case series with <10 patients and studies without a control group of breast cancer patients who did not pursue COS or ART. Quality of data and risk of bias were assessed using the Newcastle-Ottawa Assessment Scale. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 1835 records were retrieved. After excluding ineligible publications, 15 studies were finally included in the present meta-analysis (n = 4643). Among them, 11 reported the outcomes of breast cancer patients who underwent COS for fertility preservation before starting chemotherapy, and 4 the safety of ART following anticancer treatment completion. Compared to women who did not receive fertility preservation at diagnosis (n = 2386), those who underwent COS (n = 1594) had reduced risk of recurrence (RR 0.58, 95% CI 0.46-0.73) and mortality (RR 0.54, 95% CI 0.38-0.76). No detrimental effect of COS on EFS was observed (HR 0.76, 95% CI 0.55-1.06). A similar trend of better outcomes in terms of EFS was observed in women with hormone-receptor-positive disease who underwent COS (HR 0.36, 95% CI 0.20-0.65). A reduced risk of recurrence was also observed in patients undergoing COS before neoadjuvant chemotherapy (RR 0.22, 95% CI 0.06-0.80). Compared to women not exposed to ART following completion of anticancer treatments (n = 540), those exposed to ART (n = 123) showed a tendency for better outcomes in terms of recurrence ratio (RR 0.34, 95% CI 0.17-0.70) and EFS (HR 0.43, 95% CI 0.17-1.11). LIMITATIONS, REASONS FOR CAUTION: This meta-analysis is based on abstracted data and most of the studies included are retrospective cohort studies. Not all studies had matching criteria between the study population and the controls, and these criteria often differed between the studies. Moreover, rate of recurrence is reported as a punctual event and it is not possible to establish when recurrences occurred and whether follow-up, which was shorter than 5 years in some of the included studies, is adequate to capture late recurrences. WIDER IMPLICATIONS OF THE FINDINGS: Our results demonstrate that performing COS at diagnosis or ART following treatment completion does not seem to be associated with detrimental prognostic effect in young women with breast cancer, including among patients with hormone receptor-positive disease and those receiving neoadjuvant chemotherapy. STUDY FUNDING/COMPETING INTEREST(S): Partially supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC; grant number MFAG 2020 ID 24698) and the Italian Ministry of Health-5 × 1000 funds 2017 (no grant number). M.L. acted as consultant for Roche, Pfizer, Novartis, Lilly, AstraZeneca, MSD, Exact Sciences, Gilead, Seagen and received speaker honoraria from Roche, Pfizer, Novartis, Lilly, Ipsen, Takeda, Libbs, Knight, Sandoz outside the submitted work. F.S. acted as consultant for Novartis, MSD, Sun Pharma, Philogen and Pierre Fabre and received speaker honoraria from Roche, Novartis, BMS, MSD, Merck, Sun Pharma, Sanofi and Pierre Fabre outside the submitted work. I.D. has acted as a consultant for Roche, has received research grants from Roche and Ferring, has received reagents for academic clinical trial from Roche diagnostics, speaker's fees from Novartis, and support for congresses from Theramex and Ferring outside the submitted work. L.D.M. reported honoraria from Roche, Novartis, Eli Lilly, MSD, Pfizer, Ipsen, Novartis and had an advisory role for Roche, Eli Lilly, Novartis, MSD, Genomic Health, Pierre Fabre, Daiichi Sankyo, Seagen, AstraZeneca, Eisai outside the submitted work. The other authors declare no conflict of interest. The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript and decision to submit the manuscript for publication. REGISTRATION NUMBER: N/A.
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Neoplasias da Mama , Sobreviventes de Câncer , Preservação da Fertilidade , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Recidiva Local de Neoplasia , Gravidez , Estudos RetrospectivosRESUMO
BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression at post-transcriptional level, having a role in many biological processes, such as control of cell proliferation, cell cycle, and cell death. Altered miRNA expression has been reported in many neoplasms, including pituitary adenomas (PAs). PURPOSE: In this study, we aimed to evaluate the expression of 20 miRNAs involved in pathways relevant to pituitary pathophysiology, in PAs and normal pituitary tissue and to correlate their expression profile with clinical and pathological features. METHODS: Pituitary tumor samples were obtained during transphenoidal surgery from patients with non-functioning (NFPA, n = 12) and functioning (n = 11, 5 GH-, 3 ACTH-, 3 PRL-omas) PAs. The expression of selected miRNAs in PAs and in normal pituitary was analyzed by RT-qPCR. miRNAs expression was correlated with demographic, clinical, and neuroradiological data and with histopathological features including pituitary hormones immunostaining, Ki-67 proliferation index, and p53 immunohistochemistry evaluation. RESULTS: All evaluated miRNAs except miR-711 were expressed in both normal and tumor pituitary tissue. Seventeen miRNAs were significantly down-regulated in pituitary tumors compared to normal pituitary. miRNAs were differentially expressed in functioning PAs or in NFPAs, as in the latter group miR-149-3p (p = 0.036), miR-130a-3p (p = 0.014), and miR-370-3p (p = 0.026) were significantly under expressed as compared to functioning tumors. Point-biserial correlation analysis demonstrated a negative correlation between miR-26b-5p and Ki-67 (p = 0.031) and between miR-30a-5p and 'atypical' morphological features (p = 0.038) or cavernous sinus invasion (p = 0.049), while 508-5p was inversely correlated with clinical aggressiveness (p = 0.043). CONCLUSIONS: In this study, we found a significant down-regulation of 17 miRNAs in PAs vs normal pituitary, with differential expression profile related to functional status and tumor aggressiveness.
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Adenoma/genética , Adenoma/patologia , MicroRNAs/genética , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/patologia , Adenoma/diagnóstico , Adenoma/terapia , Adulto , Idoso , Proliferação de Células/genética , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Estadiamento de Neoplasias , Testes de Função Hipofisária , Hipófise/metabolismo , Hipófise/fisiologia , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/terapia , PrognósticoRESUMO
PURPOSE: Biomarkers of clinical and therapeutic outcome in acromegaly are needed. Polymorphisms or epigenetic changes of detoxification genes, such as those coding for the aryl hydrocarbon receptor (AHR) and the glutathione-S-transferase-P1 (GSTP1), could have a role in GH secreting pituitary tumors' pathophysiology and clinical expression. In this study, we assessed the contribution of GSTP1 gene promoter methylation status, per se or in combination with the occurrence of the AHR gene rs2066853 variant, on clinical features and response to somatostatin analogs (SSA) treatment in acromegaly patients. METHODS: This is an observational, retrospective study, carried out in the Endocrine Unit of an Italian University Hospital. We enrolled 77 wild-type AIP gene acromegaly patients, who have been screened for germline AHR rs2066853 variant and GSTP1 gene promoter methylation. Clinical and biochemical parameters were compared after patients' stratification according to GSTP1 methylation status and the presence of AHR rs2066853. We also evaluated the response to SSA treatment in 71 cases. RESULTS: 17 patients carried the AHR rs2066853 variant and 26 had methylated GSTP1 (GSTP1-methyl) gene promoter. GSTP1-methyl patients showed a higher prevalence of diabetes mellitus (p = 0.01), colonic polyps (p = 0.05), and were more resistant to SSA (p = 0.02) as compared to GSTP1 unmethylated patients (GSTP1-unmethyl). Patients GSTP1-unmethyl and AHR wild-type were the most sensitive to SSA treatment, while those with both GSTP1-methyl and AHR rs2066853 variant were all resistant to SSA (p = 0.01). CONCLUSIONS: In acromegaly, GSTP1 gene methylation associates with resistance to SSA treatment, especially in patients carrying also the AHR rs2066853 variant, and with increased prevalence of colonic polyps and diabetes mellitus.
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Acromegalia/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Biomarcadores/análise , Resistência a Medicamentos/genética , Glutationa S-Transferase pi/genética , Octreotida/uso terapêutico , Polimorfismo Genético , Receptores de Hidrocarboneto Arílico/genética , Acromegalia/tratamento farmacológico , Acromegalia/patologia , Antineoplásicos Hormonais/uso terapêutico , Metilação de DNA , Feminino , Seguimentos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Regiões Promotoras Genéticas , Estudos RetrospectivosRESUMO
BACKGROUND: Clinical responses to ipilimumab are variable in terms of onset, magnitude and duration. Upfront identification of patients who are more likely or unlikely to benefit from treatment is a major need. PATIENTS AND METHODS: Prospectively collected data from 720 advanced melanoma patients treated with ipilimumab 3 mg/kg within the Italian expanded access program were analyzed. The derived neutrophil-to-lymphocyte ratio (dNLR) was calculated from baseline peripheral blood cell counts, and receiver operating characteristic curve was used to evaluate the best cutoff for this marker. Patients were stratified according to dichotomized baseline absolute neutrophil counts (ANC), dNLR and their combination. The prognostic values of ANC and dNLR for survival were assessed using multivariate Cox proportional hazard models. A subgroup analysis including LDH in the models was also carried out. RESULTS: The median follow-up was 16.5 months. The optimal cutoff for dNLR was 3. Baseline ANC and dNLR were significantly associated with the outcome of ipilimumab-treated melanoma patients, in terms of disease progression and death (P < 0.0001 for all). Furthermore, for each elevated variable, prognosis worsened. Patients with both ANC ≥ 7500 and dNLR ≥ 3 had a significantly and independently increased risk of death [hazard ratio(HR) = 5.76; 95% confidence interval (CI) 4.29-7.75] and of progression (HR = 4.10; 95% CI 3.08-5.46) compared with patients with both lower ANC and dNLR. Patients with one of the two factors elevated displayed an intermediate risk of progression and death. The 1- and 2-year survival rates were 2% and 0%, respectively, for patients with ANC ≥ 7500 and dNLR ≥ 3, and 43% and 24%, respectively, for patients with both lower ANC and dNLR. CONCLUSIONS: Although these findings need to be confirmed and validated, we suggest that a neutrophil-based index may help risk-group stratification and assist disease-management strategies. Furthermore, the potential predictive value of this index for response to ipilimumab should be investigated in randomized clinical trials.
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Anticorpos Monoclonais/administração & dosagem , Biomarcadores Tumorais/sangue , Melanoma/sangue , Melanoma/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Ipilimumab , Itália , Contagem de Linfócitos , Linfócitos/patologia , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Neutrófilos/patologia , PrognósticoRESUMO
BACKGROUND: Retreatment with ipilimumab has been shown to re-establish disease control in some patients with disease progression. Here, we report the efficacy and safety of retreatment with ipilimumab 3 mg kg(-1) among patients participating in an expanded access programme in Italy. METHODS: Patients who achieved disease control during induction therapy were retreated with ipilimumab upon progression (3 mg kg(-1) every 3 weeks for up to four doses), providing they had not experienced toxicity that precluded further dosing. Tumour assessments were conducted after retreatment, and patients were monitored throughout for adverse events. RESULTS: Of 855 patients treated with ipilimumab, 51 were retreated upon disease progression. Of these, 28 (55%) regained disease control upon retreatment and 42% were alive 2 years after the first induction dose of ipilimumab; median overall survival was 21 months. Eleven patients (22%) had a treatment-related adverse event of any grade during retreatment. These were generally mild-to-moderate and resolved within a median of 4 days. No new types of toxicity were reported. CONCLUSIONS: For patients who meet predefined criteria, retreatment with ipilimumab is generally well tolerated and can translate into clinical benefit. This strategy should be compared with other therapeutic options in randomised controlled trials.
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Anticorpos Monoclonais/uso terapêutico , Melanoma/terapia , Neoplasias Cutâneas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Implementação de Plano de Saúde , Acessibilidade aos Serviços de Saúde , Humanos , Imunoterapia/métodos , Ipilimumab , Itália , Masculino , Melanoma/mortalidade , Melanoma/patologia , Pessoa de Meia-Idade , Desenvolvimento de Programas , Indução de Remissão , Retratamento , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Análise de Sobrevida , Adulto JovemRESUMO
Deep brain stimulation (DBS) can be complicated by adverse events, which are generally classified as surgical-hardware or stimulation-related. Here we report the onset of a painful cervical dystonia probably triggered by the extension wire of a subthalamic nucleus (STN)-DBS device in a woman suffering from advanced Parkinson's disease (PD). Two months after implantation of the STN-DBS device, our patient developed a painful cervical dystonia, which was not responsive to neurostimulation or to medication. No sign of infections or fibrosis was detected. A patch test with the components of the device was performed, revealing no hypersensibility. The patient was referred back to surgery to reposition the pulse generator in the contralateral subclavian region. A deeper channeling of the wire extensions produced a complete remission of the painful dystonia.
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Estimulação Encefálica Profunda/efeitos adversos , Estimulação Encefálica Profunda/instrumentação , Eletrodos Implantados/efeitos adversos , Torcicolo/etiologia , Idoso , Falha de Equipamento , Feminino , Humanos , Dor/etiologia , Doença de Parkinson/cirurgia , Doença de Parkinson/terapia , Reoperação , Núcleo Subtalâmico/lesõesRESUMO
Cerebral involvement in the course of Langerhans cell histiocytosis has been described especially in children. It is mainly characterized by hypothalamic-pituitary functional deficit, due to granuloma growth. Here we describe a rare case of adult-onset histiocytosis developing a neurodegenerative disease resembling multiple system atrophy. The patient we describe here started suffering from subtle personality changes which progressed to a severe neurological syndrome 2 years after the diagnosis of histiocytosis. Twenty years before she developed a diabetes insipidus, without any apparent cause. Brain MRI scans at the time of neurodegeneration revealed slight signal alterations at the cerebellum, especially involving the dentate nuclei and the white matter. Despite being rare, histiocytosis should be considered in adult patients with cerebellar abnormalities and/or with unexplained diabetes insipidus to rapidly discern and treat histiocytosis before the onset of its neurodegenerative, untreatable phase.