COVID-19 in patients with thymic epithelial tumors with or without Good's syndrome: a single-center retrospective study.

INTRODUCTION: Thymic epithelial tumors (TETs) are rare neoplasms often associated with immune-related disorders. Patients with Good's syndrome (GS), an adult-acquired TET-related immunodeficiency, are at a high risk of mortality due to infectious diseases. This study aims to examine COVID-19 occurrence and severity in TET patients, with or without GS. METHODS: Clinical records of TET patients referred to the Regional Coordinating Center for Rare Tumors of Campania Region were retrospectively collected. During the observation period, elapsing from March 2020 to April 2023, the following data were collected: occurrence of SARS-CoV-2 infection; COVID-19 severity, according to the National Institute of Health (NIH) illness categories; COVID-19 treatment. COVID-19 occurrence and severity were assessed in the overall population and correlated with the presence of GS and/or other immune-related dysregulations. RESULTS: Overall, 47 TET patients were included in the study; 27 of these (57.4%) had GS. All participants had received a full cycle of mRNA vaccine for SARS-CoV2., Thirty-one patients (66.0%) experienced COVID-19, of whom 18 (58.0%) had previously received a diagnosis of GS. No significant association of GS and/or other immune-related dysregulations with SARS-CoV-2 infection occurrence was detected (Fisher's exact test p = 1 and p = 0.3587, respectively). Among patients with GS, 8 (45.0%) reported a COVID-19 severity score of ≥ 3; whereas, only 1 of the 13 patients without GS (7.7%) had a severity score of ≥ 3. The correlation between presence of GS and COVID-19 severity (score 1 or 2 vs. ≥ 3) was statistically significant (p = 0.0448). No statistically significant association between COVID-19 severity and other immune-related syndromes were found (p = 1). Of note, all the hospitalized patients for NIH 4 and 5 COVID-19 had GS. CONCLUSIONS: Our data suggest that TET patients, especially those with GS, require a careful multidisciplinary monitoring for SARS-CoV-2 infection, in order to establish tailored treatments and prophylactic protocols.

Serum biomarkers of inflammation and vascular damage upon SARS-Cov-2 mRNA vaccine in patients with thymic epithelial tumors.

OBJECTIVES: Thymic epithelial tumors (TET) patients are at high risk of autoimmune and hypoimmune complications. Limited evidence is available on the potential risk of immune-related and inflammatory reactions induced by SARS-Cov-2 vaccine in this patient population. METHODS: In order to identify subjects at higher risk for vaccine complications, we prospectively evaluated a panel of serum biomarkers related to inflammation (TNF-α, IL-1ß, -6, -10, -12, and -17A, IFN-α, ß and γ, MPO, MMP-9), and vascular damage (E- and P-selectin, VEGF-A, P-ANCA and MCP-1) in 44 TET patients and in 30 healthy controls along the whole SARS-Cov-2 vaccine cycle. RESULTS: About 50 % of subjects (either TET and controls) showed an increase of serum biochemical markers of inflammation and endothelial damage with a large heterogeneity of values. Such increase appeared early, after the first dose in control subjects and later, after the second dose in TET patients (in which we observed mainly an increase of inflammatory biomarkers). The values normalized after about 3 months and did not increase after the third, booster dose. No autoimmune or vascular complications were observed in the study subjects and no difference was observed in terms of vaccine response among subjects showing serum biomarkers increase and those who experienced no changes. CONCLUSIONS: Our data highlight the relevance of Sars-Cov-2 vaccine in TET patients, as it resulted safe and prevented severe COVID-19. However, further studies are awaited to explore the mechanisms and the potential consequences of the observed increase of serum inflammatory and vascular damage biomarkers.

BRAF Gene and Melanoma: Back to the Future.

As widely acknowledged, 40-50% of all melanoma patients harbour an activating BRAF mutation (mostly BRAF V600E). The identification of the RAS-RAF-MEK-ERK (MAP kinase) signalling pathway and its targeting has represented a valuable milestone for the advanced and, more recently, for the completely resected stage III and IV melanoma therapy management. However, despite progress in BRAF-mutant melanoma treatment, the two different approaches approved so far for metastatic disease, immunotherapy and BRAF+MEK inhibitors, allow a 5-year survival of no more than 60%, and most patients relapse during treatment due to acquired mechanisms of resistance. Deep insight into BRAF gene biology is fundamental to describe the acquired resistance mechanisms (primary and secondary) and to understand the molecular pathways that are now being investigated in preclinical and clinical studies with the aim of improving outcomes in BRAF-mutant patients.

The Enigmatic Role of TP53 in Germ Cell Tumours: Are We Missing Something?

The cure rate of germ cell tumours (GCTs) has significantly increased from the late 1970s since the introduction of cisplatin-based therapy, which to date remains the milestone for GCTs treatment. The exquisite cisplatin sensitivity has been mainly explained by the over-expression in GCTs of wild-type TP53 protein and the lack of TP53 somatic mutations; however, several other mechanisms seem to be involved, many of which remain still elusive. The findings about the role of TP53 in platinum-sensitivity and resistance, as well as the reported evidence of second cancers (SCs) in GCT patients treated only with surgery, suggesting a spectrum of cancer predisposing syndromes, highlight the need for a deepened understanding of the role of TP53 in GCTs. In the following report we explore the complex role of TP53 in GCTs cisplatin-sensitivity and resistance mechanisms, passing through several recent genomic studies, as well as its role in GCT patients with SCs, going through our experience of Center of reference for both GCTs and cancer predisposing syndromes.

Management of Germ Cell Tumors During the Outbreak of the Novel Coronavirus Disease-19 Pandemic: A Survey of International Expertise Centers.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has become a public health emergency affecting frail populations, including patients with cancer. This poses the question of whether cancer treatments can be postponed or modified without compromising their efficacy, especially for highly curable cancers such as germ cell tumors (GCTs). MATERIALS AND METHODS: To depict the state-of-the-art management of GCTs during the COVID-19 pandemic, a survey including 26 questions was circulated by e-mail among the physicians belonging to three cooperative groups: (a) Italian Germ Cell Cancer Group; (b) European Reference Network-Rare Adult Solid Cancers, Domain G3 (rare male genitourinary cancers); and (c) Genitourinary Medical Oncologists of Canada. Percentages of agreement between Italian respondents (I) versus Canadian respondents (C), I versus European respondents (E), and E versus C were compared by using Fisher's exact tests for dichotomous answers and chi square test for trends for the questions with three or more options. RESULTS: Fifty-three GCT experts responded to the survey: 20 Italian, 6 in other European countries, and 27 from Canada. Telemedicine was broadly used; there was high consensus to interrupt chemotherapy in COVID-19-positive patients (I = 75%, C = 55%, and E = 83.3%) and for use of granulocyte colony-stimulating factor primary prophylaxis for neutropenia (I = 65%, C = 62.9%, and E = 50%). The main differences emerged regarding the management of stage I and stage IIA disease, likely because of cultural and geographical differences. CONCLUSION: Our study highlights the common efforts of GCT experts in Europe and Canada to maintain high standards of treatment for patients with GCT with few changes in their management during the COVID-19 pandemic. IMPLICATIONS FOR PRACTICE: Despite the chaos, disruptions, and fears fomented by the COVID-19 illness, oncology care teams in Italy, other European countries, and Canada are delivering the enormous promise of curative management strategies for patients with testicular cancer and other germ cell tumors. At the same time, these teams are applying safe and innovative solutions and sharing best practices to minimize frequency and intensity of patient contacts with thinly stretched health care capacity.

Systemic treatment of malignant gastrointestinal neuroectodermal tumour after childhood neuroblastoma: chemotherapy in malignant gastrointestinal neuroectodermal tumour.

Malignant gastrointestinal neuroectodermal tumour is an extremely rare neoplasm that arises in the wall of the small bowel, stomach or large bowel in young-aged and middle-aged adults. Histologically, it is generally characterized by monomorphic cells with clear cytoplasma, S-100 protein expression, and EWSR1 gene translocation. To the best of our knowledge, we describe for the first time, the case of a young woman with a diagnosis of metastatic gastrointestinal neuroectodermal tumour arising from ileum, who had a childhood adrenal neuroblastoma with liver, bone and lymph nodes metastasis, treated with four cycles of chemotherapy with the schedule CADO-CVP (CADO: cyclophosphamide 300 mg/m/day on days 1-5, vincristine 1,5 mg/m/day on days 1 and 5, and doxorubicin 60 mg/m/day on day 5; CVP: cisplatin 40 mg/m/day on days 1-5 and etoposide 100 mg/m/day on days 1-5) followed by right adrenal, kidney, lymph nodes and liver lesion resection, conditioning chemotherapy (melphalan-carmustine-teniposide), stem cells autologous transplantation and consecutively radiotherapy on the spine (T9 to L3) for a total of 30 Gy. For the second diagnosis of gastrointestinal neuroectodermal tumour with liver metastasis, she underwent ileal tumour resection and platinum-anthracycline based chemotherapy with initial shrinkage of liver metastasis. Unfortunately, despite the initial response and the following delivered therapies, she died for rapid progressive disease. Taking into account the late effects of past therapeutic modalities, a long-term surveillance of young child treated for neuroblastoma, is required to appreciate their overall risks of second malignancies.

Clinical features and psychological aspects of the decision-making process in stage I testicular germ cell tumors.

Testicular germ cell tumors (TGCTs) are the most prevalent malignancies in young Caucasian men. Clinical stage I (CSI) TGCTs present the highest cure rate and treatment options after orchiectomy depend on histology and risk factors. Nevertheless, the management of CSI TGCTs is controversial due to the availability of multiple treatments and the lack of randomized trials. An integrated multidisciplinary approach that includes clinicians (surgeons, radiotherapists and oncologists) and psychologists is crucial to maximize the patients' compliance and must be acknowledged with appropriate tools. The aim of our work is to review the oncological and psychological aspects of the decision-making process, discussing the fundamental role of the patient involvement in the personalized management of CSI TGCTs.

Correlative Imaging in a Patient with Cystic Thymoma: CT, MR and PET/CT Comparison.

BACKGROUND: Cystic thymoma is a rare variant of thymic neoplasm characterized by almost complete cystic degeneration with mixed internal structure. We describe a case of a 60 year-old woman with a cystic thymoma studied with advanced tomographic imaging stydies. CT, MRI and PET/CT with (18)F-FDG were performed; volumetric CT and MRI images provided better anatomic evaluation for pre-operative assessment, while PET/CT was helpful for lesion characterization based on (18)F-FDG uptake. Although imaging studies are mandatory for pre-operative evaluation of cystic thymoma, final diagnosis still remains surgical. CASE REPORT: A 60-year-old woman with recent chest pain and no history of previous disease was admitted to our departement to investigate the result of a previous chest X-ray that showed bilateral mediastinal enlargement; for this purpose, enhanced chest CT scan was performed using a 64-rows scanner (Toshiba, Aquilion 64, Japan) before and after intravenous bolus administration of iodinated non ionic contrast agent; CT images demonstrated the presence of a large mediastinal mass (11×8 cm) located in the anterior mediastinum who extended from the anonymous vein to the cardio-phrenic space, compressing the left atrium and causing medium lobe atelectasis; bilateral pleural effusion was also present. CONCLUSIONS: In conclusion, correlative imaging plays a foundamental role for the diagnostic evaluation of patient with cystic thymoma. In particular, volumetric CT and MRI studies can provide better anatomic informations regarding internal structure and local tumor spread for pre-operative assessment. Conversely, metabolic imaging using (18)F-FDG PET/CT is helpful for lesion characterization differentiating benign from malignant lesion on the basis of intense tracer uptake. The role of PET/MRI is still under investigation. However, final diagnosis still remains surgical even though imaging studies are mandatory for pre-operative patient management.

The role of immunotherapy in solid tumors: report from the Campania Society of Oncology Immunotherapy (SCITO) meeting, Naples 2014.

The therapeutic approach to advanced or metastatic solid tumors, either with chemotherapy or targeted therapies, is mainly palliative. Resistance to chemotherapy occurs very frequently and is one of the most important reasons for disease progression. Immunotherapy has the potential to mount an ongoing, dynamic immune response that can kill tumor cells for an extended time after the conventional therapy has been administered. Such a long-lasting response is potentially able to completely eradicate tumor cells, rather than producing only a temporary killing of cells. The most promising immune-based treatments are monoclonal antibodies that act as checkpoint inhibitors (e.g. ipilimumab and nivolumab), adoptive cell therapy (e.g. T-cells expressing chimeric antigen receptors) and vaccines (e.g. sipuleucel-T). Ipilimumab is currently approved for the treatment of metastatic melanoma and sipuleucel-T is approved for advanced prostate cancer. There is great interest in immunotherapy in other solid tumors, potentially used alone or in a multimodal fashion with chemotherapy and/or biological drugs. In this paper, we review recent advances in immuno-oncology in solid malignancies (except melanoma) as were discussed at the inaugural meeting of the Campania Society of Oncology Immunotherapy (SCITO).

Capecitabine plus gemcitabine in thymic epithelial tumors: final analysis of a Phase II trial.

BACKGROUND: A multi-institutional Phase II trial was initiated in 2005 to test the combination gemcitabine and capecitabine in patients with thymic epithelial malignancies (TETs). PATIENTS & METHODS: Patients with histologic confirmation of TET diagnosis by central review who had received >1 systemic chemotherapy treatment were included. Patients received oral capecitabine (650 mg/mq twice daily on days 1-14) and intravenous gemcitabine (1000 mg/mq on days 1 and 8 every 3 weeks). RESULTS: Of the 30 patients included (18 men, 12 women; median age: 57 years, range: 48-61 years), the majority (73%) had thymoma, and the remaining thymic carcinoma. Eight patients developed grade 3-4 neutropenia. A total of 12 patients had a response. Median progression-free survival was 11 months (range: 6.5-16.5). CONCLUSION: Capecitabine and gemcitabine is highly active in TETs.

Sorafenib in advanced iodine-refractory differentiated thyroid cancer: efficacy, safety and exploratory analysis of role of serum thyroglobulin and FDG-PET.

CONTEXT: Radioactive iodine is a crucial tool for treatment of differentiated thyroid cancer (DTC). In 5% of cases, DTCs lose I-131 avidity and assume an aggressive behaviour. Treatment options for iodine-refractory DTC are limited. We report the experience of off-label use of the tyrosine kinase inhibitor sorafenib for treatment of advanced iodine-refractory DTC. DESIGN: Patients with progressive DTC refractory to radioactive iodine were treated with sorafenib used off-label independently from their performance status. Primary study end-points were radiological response, progression-free survival (PFS) and safety. Secondary end-points were site-specific radiological response and overall survival (OS). An exploratory analysis of the role of serum thyroglobulin (Tg) and fluorodeoxyglucose (FDG) positron emission tomography (PET) was performed. RESULTS: A total of 17 patients were included in the study. Median follow-up was 15·5 months. Clinical benefit was obtained in 71% of subjects (30% partial response and 41% stable disease). Sorafenib was mostly well tolerated, but a high incidence of fatal events was reported (three patients died from severe bleeding events and two from cardiac arrest). Median PFS was 9 months. Median OS was 10 months. The best responses were observed in lymph nodes and lung. Baseline Tg levels and the Tg response to treatment were correlated to both radiological response and PFS. Baseline FDG-PET assessment and early FDG-PET response were correlated to radiological response. CONCLUSIONS: Sorafenib allows morphological disease control in the majority of patients with iodine-refractory DTC. Progression-free survival and overall survival were lower than in previous studies as a consequence of the worse clinical condition of our patients. Sorafenib is mostly well tolerated but could have been responsible for the reported fatal events. Baseline Tg and the Tg response to treatment could be useful for predicting morphological response and clinical outcome. Early FDG-PET response could be helpful for the timely identification of nonresponding patients.

Peg-filgrastim and cabazitaxel in prostate cancer patients.

To determine the impact of prophylaxis with granulocyte-colony stimulating growth factor (G-CSF) on the risk of febrile neutropenia in a cohort of patients enrolled at the University Federico II of Naples and treated with cabazitaxel for metastatic castration-resistant prostate cancer (mCRPC). We carried out a retrospective review of prospectively collected data of patients enrolled at our institution in a compassionate-use programme with cabazitaxel, aimed at providing early access to the drug before its commercial availability in mCRPC patients. Besides baseline clinical and demographic characteristics, data on treatment efficacy and toxicity, as well as those on the use of G-CSF per patient per cycle were extracted. Progression-free survival and overall survival were calculated using the Kaplan-Meier method. Fisher's exact test was used to explore a relationship between a single event of grade 3 or more neutropenia or febrile neutropenia and previous use of G-CSF. Univariate analysis was carried out to evaluate predictors of grade 3 or more neutropenia and/or febrile neutropenia. Of 34 patients enrolled at our institution from December 2010 to December 2011, 32 had received at least one dose of cabazitaxel and were included in the analysis. Patients received a median of 10 cabazitaxel cycles. Grade 3 or more neutropenia was common, occurring in 64.5% of patients. Three patients (9.3%) developed febrile neutropenia. Twenty-seven patients received prophylaxis with G-CSF during at least one cycle using peg-filgrastim. The risk of grade 3 or more neutropenia and/or febrile neutropenia per patient and per cycle was seven times lower when G-CSF was used. Baseline neutrophil count of less than 4570/mm was the strongest predictor of grade 3 or more neutropenia and/or febrile neutropenia. No toxic death was reported. Only one patient discontinued cabazitaxel because of an adverse event. Our analysis suggests that prophylaxis with peg-filgrastim may considerably reduce the incidence of grade 3 or more neutropenia and, possibly, of febrile neutropenia in mCRPC patients treated with cabazitaxel. Further analyses involving a larger population are warranted to confirm our results.

Tumor-to-tumor metastasis: breast cancer metastatic to thymic epithelial tumor.

Tumor-to-tumor metastasis is a rare phenomenon, with around 150 cases being reported in the literature. Breast cancer is the second most commonly reported donor tumor after lung cancer, but thymic epithelial tumors have never been reported as recipient tumors. Furthermore, the thymus is rarely affected by metastases. To our knowledge, the present report is the first case of breast cancer metastatic to thymic epithelial tumor.

Potential value of Gleason score in predicting the benefit of cabazitaxel in metastatic castration-resistant prostate cancer.

AIM: This study aimed to identify predictive/prognostic factors in castration-resistant prostate cancer patients treated with cabazitaxel. PATIENTS & METHODS: Patients were enrolled from March 2011 to December 2011 in an international expanded access program. In January 2012, when cabazitaxel became commercially available, a prospective study was initiated at University Federico II of Naples and at Rionero in Vulture Hospital. RESULTS: Forty-seven patients were enrolled in this study. Patients received a median of nine cycles of cabazitaxel. Median progression-free survival was 7.0 months (95% CI: 5.7-8.0). Seventeen patients were still alive at the time of the analysis, with a median overall survival of 14 months (95% CI: 11-16). At multivariate analysis, a higher Gleason score (≥ 8) appeared to be associated with prolonged progression-free survival (hazard ratio: 0.36; 95% CI: 0.18-0.72); however, the higher Gleason score showed no statistical impact on overall survival. CONCLUSION: We hypothesize that the Gleason score has the potential to be incorporated in the clinical decision-making process for definition of treatment strategy in docetaxel-pretreated castration-resistant prostate cancer patients. We encourage further experimentation in this setting.

Extraskeletal Ewing's sarcoma of the mediastinum: Case report.

Background: Ewing sarcoma (ES) represents the second most common malignant bone tumor in children and young adults. ES is not a frequent finding in sites different from the skeletal. Common sites of appearance of ES are lower extremities, the pelvis, paravertebral spaces and head and neck. Primary extraskeletal ES located in the anterior mediastinum are very rare. These neoplasms should be discussed in specialized contests with a high volume of patients treated. Here, we present an uncommon mediastinal mass challenging in its characterization and management. Case description: A thirty-year-old woman performed a thoracic CT scan for dyspnea and persistent cough. Imaging showed a solid mass of 14 x 11 cm involving the left thorax with mediastinal deviation to the right side. Patient underwent an en bloc resection of the mass. Initial histological examination was suggestive for B3 thymoma/thymic carcinoma. Patient was then referred to our rare tumor reference center where a histological review excluded the diagnosis of thymic/thymoma neoplasms meanwhile a third revision assessed a diagnosis of ES. Patient refused adjuvant chemotherapy due to her desire of maternity and radiation therapy was not indicated because surgery was performed too many months earlier. A close follow-up was considered. After a few months the patient relapsed and first line chemotherapy was proposed. She reached a complete response at the first evaluation maintained also at the end of the protocol. In order to consolidate the obtained response, high dose chemotherapy followed by autologous stem cell transplantation (HDCT/ASCT) was suggested and the patient agreed. Conclusions: This case underlined that, potentially, ES can arise from any soft tissue site in the body, even in rare sites such as mediastinum. The evaluation of expert centers was critical to establish a correct diagnosis and therapeutic approach in this complex case. Taking into account the time lasting from the diagnosis and the aggressiveness of this kind of neoplasm, frequently relapsing, the patient after a multidisciplinary discussion was a candidate for a multimodal treatment.

Immunocytometric analysis of patients with thymic epithelial tumors revealed that COVID-19 vaccine booster strongly enhanced the immune response.

Background: Thymic epithelial tumors (TETs) are rare malignancies with heterogeneous clinical manifestations. The high frequency of autoimmune paraneoplastic disorders observed in such patients requires caution when using COVID-19 vaccines. Furthermore, TETs are often associated with severe immunodeficiency, making it difficult to predict vaccine immunization. Therefore, we aimed to evaluate immune response to COVID-19 vaccine in patients with TETs. Methods: We conducted a prospective study enrolling patients who underwent the SARS-Cov-2 mRNA full vaccine cycle (two doses plus a booster after 6 months of BNT162b2). All patients were enrolled before receiving 1st vaccine dose and were followed over the vaccination cycle for up to 6 months after the booster dose to i) assess humoral and cellular responses, ii) define biomarkers predictive of effective immunization, and iii) evaluate the safety of the vaccine. Results: At the end of the full vaccine cycle, 27 (61.4%) patients developed humoral and 38 (86.4%) cellular responses (IFN γ release by stimulated cells) and showed an increase in activated TH1 and TH17 cells, particularly significant after the booster dose. The number of B and T lymphocytes at baseline was predictive of humoral and cellular responses, respectively. Patients with no evidence of tumor lesions had a higher probability of achieving a humoral response than those with evidence of the disease. Furthermore, the percentage of patients with immune-related disorders (75%), particularly Good's syndrome (47.7%) and myasthenia gravis (29.5%), did not change over the entire vaccine cycle. Overall, 19 of the 44 enrolled patients (43.2%) had COVID-19 during the observation period; none required hospitalization or oxygen support, and no fatalities were observed. Conclusion: SARS-Cov-2 mRNA vaccine determines the immune responses in patients with TET, particularly after the booster dose, and in patients with no evidence of tumor lesions. Preliminary analysis of B and T lymphocytes may help identify patients who have a lower probability of achieving effective humoral and cellular responses and thus may need passive immunization. The vaccine prevented severe COVID-19 infection and is safe.

Shifting from a Biological-Agnostic Approach to a Molecular-Driven Strategy in Rare Cancers: Ewing Sarcoma Archetype.

Sarcomas of the thoracic cavity are rare entities that predominantly affect children and young adults. They can be very heterogeneous encompassing several different histological entities. Ewing Sarcoma (ES) can potentially arise from every bone, soft tissue, or visceral site in the body. However, it represents an extremely rare finding when it affects the thoracic cavity. It represents the second most frequent type of thoracic sarcoma, after chondrosarcoma. ES arises more frequently in sites that differ from the thoracic cavity, but it displays the same biological features and behavior of extra-thoracic ones. Current management of ES often requires a multidisciplinary treatment approach including surgery, radiotherapy, and systemic therapy, as it can guarantee local and distant disease control, at least transiently, although the long-term outcome remains poor. Unfortunately, due to the paucity of clinical trials purposely designed for this rare malignancy, there are no optimal strategies that can be used for disease recurrence. As a result of its complex biological features, ES might be suitable for emerging biology-based therapeutic strategies. However, a deeper understanding of the molecular mechanisms driving tumor growth and treatment resistance, including those related to oncogenic pathways, epigenetic landscape, and immune microenvironment, is necessary in order to develop new valid therapeutic opportunities. Here, we provide an overview of the most recent therapeutic advances for ES in both the preclinical and clinical settings. We performed a review of the current available literature and of the ongoing clinical trials focusing on new treatment strategies, after failure of conventional multimodal treatments.

Impaired Seroconversion After Severe Acute Respiratory Syndrome Coronavirus 2 mRNA Vaccine in Patients With Thymic Epithelial Tumors.

INTRODUCTION: Thymic epithelial tumors (TETs) are rare malignancies associated with dysregulation of the immune system and humoral- and cell-mediated immunity abnormalities. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine is effective in preventing coronavirus disease 2019 morbidity and mortality. The aim of this study was to evaluate the seroconversion in patients with TET after two doses of mRNA vaccine. METHODS: This is a prospective study in which consecutive patients with TET were enrolled before receiving the first dose of SARS-CoV-2 mRNA vaccine (BNT162b2 by Pfizer-BioNTech). SARS-CoV-2 spike-binding immunoglobulin (Ig)G antibody serologic levels were analyzed at different time points, including before first vaccine dose (T0), 1 month after the second dose (T2), and 3 months after the second dose (T3). RESULTS: Overall, 39 patients were included in the analysis. All patients had negative antibody titer results at T0. There were 19 patients (48.7%) in the follow-up with no residual tumor lesion/s (referred as no evidence of disease), and 20 (51.3%) had evidence of disease (ED) and were receiving systemic treatment. Dysregulations of the immune system were diagnosed in 29 patients (74.4%) with Good syndrome (GS) being the most frequent immune disorder (48.7%). At univariate analysis, lack of seroconversion at T2 was significantly associated with ED (p < 0.001) and with GS (p = 0.043). A significant association with impaired seroconversion was confirmed at multivariate analysis for ED (p = 0.00101) but not for GS (p = 0.625). CONCLUSIONS: Our data revealed that patients with TET with ED had substantially higher probability of impaired seroconversion after SARS-CoV-2 mRNA vaccine as compared with patients with no evidence of disease.

Combination of docetaxel and cetuximab for penile cancer: a case report and literature review.

Guidelines on the treatment of metastatic squamous cell carcinoma of the penis are limited to a few prospective trials. Cisplatin-based regimens represent the standard of treatment with promising activity of taxanes. Recently, epidermal growth factor receptor overexpression has been shown in these patients. We treated an elderly man with a docetaxel-cetuximab combination after failure of the cisplatin regimen. We observed a necrosis of the inguinal lymph nodes and a reduction of (18)F-fluorodeoxyglucose uptake at PET/CT scan. Only mild mucositis and skin toxicity had been detected. Our case report, the first in the literature, shows that this combination is active and well tolerated in penile squamous cell carcinoma.