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BACKGROUND: Current treatment recommendations for high grade non-metastatic osteosarcoma include perioperative chemotherapy and surgery. Despite this intensive protocol, approximately 40% of patients will relapse. The addition of the immunomodulator mifamurtide to adjuvant cytotoxic chemotherapy was associated with a significant improvement in 6-year overall survival (OS) in young patients with resectable osteosarcoma, leading to its approval in Europe and other countries. Very limited real-world data are reported on its use. METHODS: We retrospectively evaluated data from osteosarcoma patients who received mifamurtide in the adjuvant setting. Data were obtained from medical records in 2 high-volume bone sarcoma centers. The aim of this study was to collect real-world data on mifamurtide safety and efficacy in Greece. RESULTS: We identified 15 patients with completely resected osteosarcoma who received mifamurtide from September 2015 to January 2020. Median age at diagnosis was 24 years old (16-76). Osteosarcoma arose in the lower extremities (n = 12), in the upper extremities (n = 2) or in the ilium (n = 1). The majority of patients (n = 13) received cisplatin/doxorubicin/methotrexate as perioperative chemotherapy and the remaining patients cisplatin/doxorubicin. After a median follow-up of 46.9 months (range, 32.8-61.1), the median recurrence-free survival was 58.7 months (range, 18.5-98.8) and the median OS 64.1 months (range, 25.6-102.6). Except for fever and chills, the only adverse event probably related to mifamurtide was pericarditis (n = 1). CONCLUSIONS: Mifamurtide was well tolerated in a Greek osteosarcoma population, including patients older than 30 years. The small sample size and the non-comparative design do not allow drawing conclusions on the drug benefit in terms of survival.
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Neoplasias Ósseas , Osteossarcoma , Acetilmuramil-Alanil-Isoglutamina/análogos & derivados , Adjuvantes Imunológicos/uso terapêutico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Quimioterapia Adjuvante , Cisplatino/uso terapêutico , Doxorrubicina/uso terapêutico , Humanos , Fatores Imunológicos/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Osteossarcoma/tratamento farmacológico , Osteossarcoma/patologia , Fosfatidiletanolaminas , Estudos Retrospectivos , Adulto JovemRESUMO
The oropharynx has become the leading primary site for Human Papilloma Virus (HPV)-associated head and neck cancer. HPV positive oropharyngeal squamous cell carcinoma (HPV+ OSCC) has emerged as an epidemic not easily recognized by many physicians, resulting in delays in diagnosis and management. HPV+ OSCC traditionally refers to younger, healthier patients with high economic status and high-risk sexual behavior and is related to improved prognosis. De-intensification strategies are being evaluated in ongoing clinical trials and if validated, might help spare severe morbidity associated with current cisplatin-based chemoradiotherapy, which is the standard of care for all patients with locally advanced head and neck cancer. On the other hand, whether HPV status represents an important prognostic factor for non-oropharyngeal sites remains to be elucidated.
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Alphapapillomavirus/efeitos dos fármacos , Alphapapillomavirus/efeitos da radiação , Carcinoma de Células Escamosas/terapia , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias Orofaríngeas/terapia , Infecções por Papillomavirus/terapia , Alphapapillomavirus/fisiologia , Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia/métodos , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Estadiamento de Neoplasias , Neoplasias Orofaríngeas/complicações , Neoplasias Orofaríngeas/patologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Prognóstico , Análise de SobrevidaRESUMO
OPINION STATEMENT: The discovery and antibody targeting of immune regulatory molecules such as programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) pathways have led to clinically meaningful anti-cancer results. Rapid advances are being made in a variety of tumor types resulting in regulatory approvals in melanoma, non small cell lung cancer, and renal cell cancer. Numerous ongoing studies are expected to establish the worth of PD-1 pathway inhibitors in other tumor types as well as in combinations with approved agents. Head and neck squamous cell carcinoma (HNSCC) represents a complex group of malignancies characterized by profound immunosuppression and is an excellent candidate for investigation in this exciting field. However, given the fact that a subset of patients will likely benefit, it is critical to focus on biomarker development for appropriate patient selection and facilitation of trial design. As immunotherapy is settling in cancer treatment, immune checkpoint inhibitors are emerging as one of the most promising agents.
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Antineoplásicos/uso terapêutico , Biomarcadores Tumorais , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/metabolismo , Terapia de Alvo Molecular , Anticorpos Monoclonais/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Antígeno CTLA-4/antagonistas & inibidores , Ensaios Clínicos como Assunto , Terapia Combinada , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/imunologia , Humanos , Fatores Imunológicos/uso terapêutico , Imunomodulação/efeitos dos fármacos , Imunoterapia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Radioterapia , Resultado do TratamentoRESUMO
Glioblastoma (GB) is the most common and most aggressive primary brain tumor in adults, with an overall survival almost 14.6 months. Optimal resection followed by combined temozolomide chemotherapy and radiotherapy, also known as Stupp protocol, remains the standard of treatment; nevertheless, resistance to temozolomide, which can be obtained throughout many molecular pathways, is still an unsurpassed obstacle. Several factors influence the efficacy of temozolomide, including the involvement of other DNA repair systems, aberrant signaling pathways, autophagy, epigenetic modifications, microRNAs, and extracellular vesicle production. The blood-brain barrier, which serves as both a physical and biochemical obstacle, the tumor microenvironment's pro-cancerogenic and immunosuppressive nature, and tumor-specific characteristics such as volume and antigen expression, are the subject of ongoing investigation. In this review, preclinical and clinical data about temozolomide resistance acquisition and possible ways to overcome chemoresistance, or to treat gliomas without restoration of chemosensitinity, are evaluated and presented. The objective is to offer a thorough examination of the clinically significant molecular mechanisms and their intricate interrelationships, with the aim of enhancing understanding to combat resistance to TMZ more effectively.
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Stimulation of the antitumor activity of the immune system using immune checkpoint inhibitors (ICIs) has proven efficacy in the treatment of multiple types of cancer, inducing the speedily expanding approval of therapeutic indications for ICIs. The literature regarding the immune-related toxicities and nephrotoxicity of ICIs is limited. Herein, we present a patient with lung cancer treated with atezolizumab, an IgG1 monoclonal antibody aimed at the programmed death ligand 1 (PD-L1), who presented with vasculitic skin rash and rapidly deteriorating renal function, new onset of significant glomerular hematuria and proteinuria. The renal biopsy revealed acute necrotizing pauci-immune vasculitis, with fibrinoid necrosis. The patient received a course of high-dose glucocorticoids with recovery of renal function and skin lesions. Further immunosuppressive therapy was withheld, due to active malignancy in the lung, while oncology consultation recommended the continuation of treatment with atezolizumab, as the patient had shown substantial response.
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OBJECTIVES: The aim of this pilot study was to evaluate the presence of somatic mutations in matched tumor and circulating DNA (ctDNA) samples from patients with primary head and neck squamous cell carcinoma (HNSCC) and assess the association of changes in ctDNA levels with survival. MATERIALS AND METHODS: Our study included 62 patients with stage I-IVB HNSCC treated with surgery or radical chemoradiotherapy with curative intent. Plasma samples were obtained at baseline, at the end of treatment (EOT), and at disease progression. Tumor DNA was extracted from plasma (ctDNA) and tumor tissue (tDNA). The Safe Sequencing System was used assess the presence of pathogenic variants in four genes (TP53, CDKN2A, HRAS and PI3KCA) in both ctDNA and tDNA. RESULTS: Forty-five patients had available tissue and plasma samples. Concordance of genotyping results between tDNA and ctDNA at baseline was 53.3%. TP53 mutations were most commonly identified at baseline in both ctDNA (32.6%) and tDNA (40%). The presence of mutations in this restricted set of 4 genes in tissue samples at baseline was associated with decreased overall survival (OS) [median 58.3 months for patients with mutations vs. 89 months for patients without mutations, p < 0.013]. Similarly, patients presenting with mutations in ctDNA had shorter OS [median 53.8 vs. 78.6 months, p < 0.037]. CtDNA clearance at EOT did not show any association with PFS or OS. CONCLUSIONS: Liquid biopsy enables real-time molecular characterization of HNSCC and might predict survival. Larger studies are needed to validate the utility of ctDNA as a biomarker in HNSCC.
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Carcinoma Pulmonar de Células não Pequenas , DNA Tumoral Circulante , Neoplasias de Cabeça e Pescoço , Neoplasias Pulmonares , Humanos , DNA Tumoral Circulante/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Neoplasias Pulmonares/genética , Projetos Piloto , Mutação , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/terapia , Biomarcadores Tumorais/genéticaRESUMO
Purpose: We conducted a phase II randomized noncomparative window of opportunity (WOO) trial to evaluate the inhibition of cellular proliferation and the modulation of immune microenvironment after treatment with olaparib alone or in combination with cisplatin or durvalumab in patients with operable head and neck squamous cell carcinoma (HNSCC). Experimental Design: Forty-one patients with HNSCC were randomized to cisplatin plus olaparib (arm A), olaparib alone (arm B), no treatment (arm C) or durvalumab plus olaparib (arm D). The primary endpoint was to evaluate the percentage of patients in each arm that achieved a reduction of at least 25% in Ki67. Secondary endpoints included objective response rate (ORR), safety, and pathologic complete response (pCR) rate. Paired baseline and resection tumor biopsies and blood samples were evaluated for prespecified biomarkers. Results: A decrease in Ki67 of at least 25% was observed in 44.8% of treated patients, as measured by quantitative immunofluorescence. The ORR among treated patients was 12.1%. pCR was observed in 2 patients. Two serious adverse events occurred in 2 patients.Programmed death ligand 1 (PD-L1) levels [combined positive score (CPS)] were significantly higher after treatment in arms A and D. Expression of CD163 and colony-stimulating factor 1 receptor (CSF1R) genes, markers of M2 macrophages, increased significantly posttreatment whereas the expression of CD80, a marker of M1 macrophages, decreased. Conclusion: Preoperative olaparib with cisplatin or alone or with durvalumab was safe in the preoperative setting and led to decrease in Ki67 of at least 25% in 44.8% of treated patients. Olaparib-based treatment modulates the tumor microenvironment leading to upregulation of PD-L1 and induction of protumor features of macrophages. Significance: HNSCC is characterized by defective DNA repair pathways and immunosuppressive tumor microenvironment. PARP inhibitors, which promote DNA damage and "reset" the inflammatory tumor microenvironment, can establish an effective antitumor response. This phase II WOO trial in HNSCC demonstrated the immunomodulatory effects of PARP inhibitor-induced DNA damage. In this chemo-naïve population, PARP inhibitor-based treatment, reduced tumor cell proliferation and modulated tumor microenvironment. After olaparib upregulation of PD-L1 and macrophages, suggests that combinatorial treatment might be beneficial. Synopsis: Our WOO study demonstrates that preoperative olaparib results in a reduction in Ki67, upregulation of PD-L1 CPS, and induction of protumor features of macrophages in HNSCC.
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Antineoplásicos , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Cisplatino/efeitos adversos , Antígeno B7-H1 , Inibidores de Poli(ADP-Ribose) Polimerases , Antígeno Ki-67 , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Microambiente TumoralRESUMO
In August 2009, one case of autochthonous malaria due to Plasmodium vivax was diagnosed in Greece in a young woman residing in the Eastern Attica region. The source of infection could not be identified. No other autochthonous malaria cases have been described in the Attica region since 1974. This was a sporadic case with no evidence of further local transmission, and no more cases have been reported in Attica up to now, two years later.
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Malária Vivax/diagnóstico , Plasmodium vivax/isolamento & purificação , Adolescente , Feminino , Grécia , Humanos , Malária Vivax/patologia , Microscopia , Parasitemia/diagnóstico , Parasitemia/parasitologia , Parasitemia/patologiaRESUMO
Many studies have evaluated the clinical implications of lymph node ratio (LNR) as a prognostic factor in patients with oral squamous cell carcinoma (OSCC). The main purpose of this systematic review and meta-analysis was to address LNR as a prognosticator in patients with OSCC. A systematic search was conducted in the following databases: PubMed, EMBASE, Google Scholar, OpenGrey, Cochrane library, and ClinicalTrials.gov, and studies between 2009 and 2020 were sought. The pooled relative risk was calculated along with 95% confidence intervals for the following endpoints: overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), distant metastasis-free survival (DMFS), locoregional disease-free survival (LRDFS), local recurrence-free survival (LRFS), and recurrence-free survival (RFS) according to the random-effects model (Der Simonian-Laird approach). Subgroup and meta-regression analyses were performed as well. Finally, 32 cohort studies were eligible, which included 20,994 patients with OSCC. Patients were subdivided into two categories, group YES (studies that included in their analysis only patients with positive lymph nodes) and group NO (studies that did not exclude LNR = 0 patients). In the group YES, patients with high LNR had shorter OS (RR = 1.68, 95% CI: 1.47-1.91), DFS (RR = 1.68, 95% CI: 1.42-1.99), DSS (RR = 1.94, 95% CI: 1.56-2.42), DMFS (RR = 1.83, 95% CI: 1.13-2.96), LRDFS (RR = 1.55, 95% CI: 1.10-2.20), and LRFS (RR = 1.73, 95% CI: 1.41-2.13) compared to patients with low LNR. In the group NO, patients with high LNR in comparison had shorter OS (RR = 2.38, 95% CI: 1.99-2.85), DFS (RR = 2.04, 95% CI: 1.48-2.81), and DSS (RR = 2.90, 95% CI: 2.35-3.57) compared to patients with low LNR. Based on those findings, LNR might be an independent prognostic factor for OS in patients with OSCC and could be incorporated into future classification systems for better risk stratification.
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Sarcomas are a group of rare mesenchymal malignant tumors that arise from transformed cells of the mesenchymal connective tissue, which are challenging to treat. The majority of sarcomas are soft tissue sarcomas (STSs; 75%) and this heterogeneous group of tumors is further comprised of gastrointestinal stromal tumors (~15%) and bone sarcomas (10%). Although surgery remains the current primary therapeutic approach for localized disease, recurrent, metastatic and refractory sarcomas require cytotoxic chemotherapy, which usually yields poor results. Therefore the efficiency of sarcoma treatment imposes a difficult problem. Furthermore, even though progress has been made towards understanding the underlying molecular signaling pathways of sarcoma, there are limited treatment options. The aim of the present study was therefore to perform a systematic literature review of the available clinical evidence regarding the role of tyrosine kinase inhibitors (TKIs) in patients with recurrent or refractory STSs and bone sarcomas over the last two decades. Tyrosine kinases are principal elements of several intracellular molecular signaling pathways. Deregulation of these proteins has been implicated in driving oncogenesis via the crosstalk of pivotal cellular signaling pathways and cascades, including cell proliferation, migration, angiogenesis and apoptosis. Subsequently, small molecule TKIs that target these proteins provide a novel potential therapeutic approach for several types of tumor by offering significant clinical benefits. Among the eligible articles, there were 45 prospective clinical trials, primarily multicentric, single arm, phase II and non-randomized. Numerous studies have reported promising results regarding the use of TKIs, mainly resulting in disease control in patients with STSs. The lack of randomized clinical trials demonstrates the ambiguous efficiency of various studied treatment options, which therefore currently limits the approved drugs used in clinical practice. Research both in clinical and preclinical settings is needed to shed light on the underlying molecular drivers of sarcomagenesis and will identify novel therapeutic approaches for pretreated patients.
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BACKGROUND: Cancer is associated with early changes in the cardiovascular system (CV) before overt cardiotoxicity. Endothelial dysfunction is induced by chemotherapeutic regimens but there is no data for endothelial glycocalyx in cancer. METHODS: Sixty-four patients with cancer (65.6% with solid tumors and 34.4% with hematological malignancies) and 32 controls from the outpatient cardiology clinic were included in the study. The perfused boundary region (PBR) of the sublingual arterial microvessels, Pulse Wave Velocity (PWV) and augmentation index (AI) were measured. A standard transthoracic echocardiogram plus assessment of global longitudinal strain (GLS) of all cardiac chambers were performed. RESULTS: There was no difference in the baseline profile (age, sex, smoking, hypertension, diabetes, hyperlipidemia and coronary artery disease) and in the echocardiographic parameters between the two groups, with the exception of left atrial volume (33.3 ± 13 in cancer patients vs 27.6 ± 6.5 ml/m2 in controls). PBR 5-25 and PBR 20-25 were significantly increased in cancer patients vs controls (2.11 ± 0.36 vs 1.97 ± 0.21 µm, p = 0.025 and 2.65 ± 0.48 vs 2.40 ± 0.36 µm, p = 0.012, respectively). Endothelial glycocalyx thickness impairment was independent of traditional CV risk factors and anticancer therapy, but proportional to disease stage (r = 0.337, p = 0.044). However, there was no difference in arterial stiffness between the two groups (PWV 10.74 ± 4.11 vs 11.26 ± 3.38 m/s, p = 0.539 and AI 11.28 ± 28.87 vs 15.38 ± 18.8 %, p = 0.470). CONCLUSIONS: Endothelial function as assessed by endothelial glycocalyx thickness is significantly impaired in cancer patients without overt cardiotoxicity. This implies that PBR might be useful for the early assessment of microvascular and endothelial toxicity of cancer.
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Glicocálix , Rigidez Vascular , Cardiotoxicidade/patologia , Humanos , Microvasos , Análise de Onda de PulsoRESUMO
This non-interventional, multicenter, prospective study aimed to evaluate the real-world activity of trabectedin, and its impact on symptom burden and quality of life in patients with advanced soft tissue sarcoma (aSTS) treated in routine clinical settings in Greece. Patients with histologically confirmed aSTS newly initiated on trabectedin were enrolled. The primary endpoint was progression-free survival (PFS) rate at 6 months. Secondary endpoints included PFS rate at 3 months, median PFS, objective response rate (ORR), disease control rate (DCR), overall survival (OS), and an assessment of the impact of treatment on health-related quality of life (HRQoL), cancer-related symptom burden and symptom interference with function, as well as all-cause treatment discontinuation rate. A total of 64 eligible patients from 13 Greek centers were evaluated. Patients received a median of three trabectedin cycles per patient (interquartile range [IQR]: 2.0-6.0). Median PFS was 6.6 months with 67.9% and 51.2% of patients free from progression at 3 and 6 months, respectively. ORR was 7.8% and DCR 21.9%. Median OS was 13.1 months. No significant changes from enrolment were noted in HRQoL scores. In total, 30 patients (46.9%) had at least one trabectedin-related adverse drug reaction (ADR) and 9 (14.1%) at least one serious ADR. The treatment discontinuation rate due to toxicity was 9.4%. These results suggest that trabectedin is an active treatment with clinically meaningful benefits in patients with aSTS with no new safety signals.
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HPV-related head and neck squamous cell carcinoma (HNSCC) has emerged as a diverse clinical and biological disease entity, mainly in young patients with oropharyngeal tumors who are nonsmokers and nondrinkers. Indeed, during the past few years, the pendulum has shifted towards a new epidemiological reality, the "HPV pandemic", where the majority of oropharyngeal squamous cell carcinomas (OPSCCs) are attributed to HPV. The oncogenic potential of the virus is associated to its capacity of integrating oncogenes E6 and E7 into the host cell, leading to the inactivation of several tumor suppressor genes, such as Rb. HPV status can affect prognosis in OPSCC, but its role as a predictive biomarker remains to be elucidated. Given the favorable prognosis associated with HPV-positive disease, the concept of de-escalation treatment strategies has been developed with the primary intent being the reduction of treatment-related long-term toxicities. In this review, we aim to depict current data regarding treatment de-escalation in HPV-associated OPSCC and discuss ongoing clinical trials.
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Neoplasias de Cabeça e Pescoço/virologia , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/complicações , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Carcinoma de Células Escamosas/virologia , Humanos , Oncogenes , Neoplasias Orofaríngeas/virologia , Papillomaviridae/classificação , Papillomaviridae/genética , Proteínas E7 de Papillomavirus/genética , Prognóstico , Proteínas Repressoras/genéticaRESUMO
The aim of this paper is to prospectively evaluate the efficacy and safety of percutaneous computed tomography (CT)-guided radiofrequency (RF) neurolysis of splanchnic nerves as a single treatment for pain reduction in patients with pancreatic cancer. Patients with pancreatic ductal adenocarcinoma suffering from abdominal pain refractory to conservative medication who underwent CT-guided neurolysis of splanchnic nerves by means of continuous radiofrequency were prospectively evaluated for pain and analgesics reduction as well as for survival. In all patients, percutaneous neurolysis was performed with a bilateral retrocrural paravertebral approach at T12 level using a 20 Gauge RF blunt curved cannula with a 1cm active tip electrode. Self-reported pain scores were assessed before and at the last follow-up using a pain inventory with numeric visual scale (NVS) units. The mean patient age was 65.4 ± 10.8 years (male-female: 19-11). The mean pain score prior to RF neurolysis of splanchnic nerves was 9.0 NVS units; this score was reduced to 2.9, 3.1, 3.6, 3.8, and 3.9 NVS units at 1 week, 1, 3, 6, and 12 months respectively (p < 0.001). Significantly reduced analgesic usage was reported in 28/30 patients. Two grade I complications were reported according to the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) classification system. According to the results of the present study, solely performed computed tomography-guided radiofrequency neurolysis of splanchnic nerves can be considered a safe and efficacious single-session technique for pain palliation in patients with pancreatic ductal adenocarcinoma suffering from abdominal pain refractory to conservative medication. Although effective in pain reduction the technique seems to have no effect upon survival improvement.
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Osteosarcoma is the most frequent primary bone cancer, mainly affecting those of young ages. Although surgery combined with cytotoxic chemotherapy has significantly increased the chances of cure, recurrent and refractory disease still impose a tough therapeutic challenge. We performed a systematic literature review of the available clinical evidence, regarding treatment of recurrent and/or refractory osteosarcoma over the last two decades. Among the 72 eligible studies, there were 56 prospective clinical trials, primarily multicentric, single arm, phase I or II and non-randomized. Evaluated treatment strategies included cytotoxic chemotherapy, tyrosine kinase and mTOR inhibitors and other targeted agents, as well as immunotherapy and combinatorial approaches. Unfortunately, most treatments have failed to induce objective responses, albeit some of them may sustain disease control. No driver mutations have been recognized, to serve as effective treatment targets, and predictive biomarkers of potential treatment effectiveness are lacking. Hopefully, ongoing and future clinical and preclinical research will unlock the underlying biologic mechanisms of recurrent and refractory osteosarcoma, expanding the therapeutic choices available to pre-treated osteosarcoma patients.
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Background: We sought to compare patterns of response to immune checkpoint inhibitors (ICI) with respect to clinical and genomic features in a retrospective cohort of patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Methods: One hundred seventeen patients with R/M HNSCC treated with ICI were included in this study. Tumor growth kinetics (TGK) prior to and TGK upon immunotherapy (IO) was available for 49 patients. The TGK ratio (TGKR, the ratio of tumor growth velocity before and upon treatment) was calculated. Hyperprogression (HPD) was defined as TGKR ≥ 2. Results: HPD was documented in 18 patients (15.4% of the whole cohort). Patients with HPD had statistically significant shorter progression free survival (PFS) (median PFS 1.8 months (95% CI, 1.03-2.69) vs. 6.1 months for patients with non-HPD (95% CI, 4.78-7.47), p = 0.0001) and overall survival (OS) (median OS 6.53 months (95% CI, 0-13.39) vs. 15 months in patients with non HPD (95% CI, 7.1-22.8), p = 0.0018). In a multivariate Cox analysis, the presence of HPD remained an independent prognostic factor (p = 0.049). Primary site in the oral cavity and administration of ICI in the second/third setting were significant predictors of HPD in multivariate analysis (p = 0.028 and p = 0.012, respectively). Genomic profiling revealed that gene amplification was more common in HPD patients. EGFR gene amplification was only observed in HPD patients, but the number of events was inadequate for the analysis to reach statistical significance. The previously described MDM2 amplification was not identified. Conclusions: HPD was observed in 15.4 % of patients with R/M HNSCC treated with IO and was associated with worse PFS and OS. EGFR amplification was identified in patients with HPD.
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BACKGROUND: nasopharyngeal carcinoma (NPC) is a complex disease entity that mainly predominates in endemic regions. Real-world data with immunotherapy from nonendemic regions are limited. METHODS: we collected data from patients with recurrent/metastatic (R/M) NPC treated at a center in Greece and 8 centers in Italy. Between 2016 and 2021, 46 patients who were treated with at least one cycle of immune checkpoint inhibitors (ICI) were identified. Herein, we present our results and a review of the literature. RESULTS: assessment of response was available in 42 patients. Overall, 11 patients responded to immunotherapy (Overall Response Rate-ORR 26.2%). Three patients had complete response (CR), and 8 patients had partial response (PR). Disease control rate (DCR) was 61.9%. Median Progression Free Survival (PFS) was 5.6 months and median Overall Survival (OS) was 19.1 months. Responders to ICI improved PFS and OS as compared to that of nonresponders. A lower probability of responding to ICI was shown in patients with more than three metastatic sites (p = 0.073), metastatic disease at initial diagnosis, (p = 0.039) or EBV DNA positive before ICI initiation, (p = 0.074). Decline in EBV DNA levels was found to be statistically significant associated with best response to ICI (p = 0.049). Safety was manageable. CONCLUSIONS: among 46 patients with R/M NPC treated with immunotherapy in two nonendemic regions, ORR was 26.2% and durable responses were observed. Low disease burden could serve as a biomarker for response to ICI.
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Imunoterapia , Carcinoma Nasofaríngeo/imunologia , Carcinoma Nasofaríngeo/terapia , Idoso , Feminino , Grécia , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/efeitos adversos , Itália , Masculino , Metástase Neoplásica , Intervalo Livre de Progressão , Análise de SobrevidaRESUMO
The tumor microenvironment (TME) encompasses cellular and non-cellular components which play an important role in tumor evolution, invasion, and metastasis. A complicated interplay between tumor cells and adjacent TME cells, such as stromal cells, immune cells, inflammatory cells, and cytokines, leads to severe immunosuppression and the proliferation of cancer cells in several solid tumors. An immunosuppressive TME has a significant impact on treatment resistance and may guide response to immunotherapy. In head and neck cancer (HNC), immunotherapeutic drugs have been incorporated in everyday clinical practice. However, despite an exceptional rate of durable responses, only a low percentage of patients respond. In this review, we will focus on the complex interactions occurring in this dynamic system, the TME, which orchestrate key events that lead to tumor progression, immune escape, and resistance. Furthermore, we will summarize current clinical trials that depict the TME as a potential therapeutic target for improved patient selection.
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INTRODUCTION: Immune checkpoint inhibitors (ICIs) have rapidly changed the treatment landscape, demonstrating dramatic clinical efficacy in various cancers. AREAS COVERED: In urothelial cancer (UC), several ICIs have been approved in platinum refractory disease and also as first-line therapy in patients that fulfill the criteria for cisplatin ineligibility. Atezolizumab is a monoclonal antibody that targets the immune checkpoint Programmed Cell Death Ligand-1 (PD-L1) and has been currently approved for advanced UC, non-small cell lung cancer, small cell lung cancer, and triple-negative breast cancer. Herein, we provide a summary of the mechanism of action, safety, and clinical efficacy of atezolizumab in UC. EXPERT OPINION: Atezolizumab is a drug with a favorable toxicity profile and will obtain more indications in the future in UC and other cancers. Treating physicians should be aware of treatment-related and immune-related adverse events associated with the drug.
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Anticorpos Monoclonais Humanizados/administração & dosagem , Carcinoma de Células de Transição/tratamento farmacológico , Neoplasias Urológicas/tratamento farmacológico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/farmacologia , Antígeno B7-H1/imunologia , Carcinoma de Células de Transição/patologia , Humanos , Inibidores de Checkpoint Imunológico/administração & dosagem , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/farmacologia , Neoplasias Urológicas/patologiaRESUMO
Immune checkpoint inhibitors (ICIs) are among the most promising drugs in the field of immuno-oncology; they represent monoclonal antibodies that modulate the effects of immune checkpoints, such as Programmed Cell Death protein 1 (PD-1) which is a co-inhibitory signal responsible for immune suppression. Dermatologic immune-related toxicity is a common type of toxicity associated with these agents. However, oral skin reactions are rare. Herein, we describe an unusual case of a patient that developed oral lichen planus during treatment with anti-PD-1 inhibitor nivolumab.