BackgroundIn the midst of the COVID-19 pandemic, patients with cancer are regarded as a highly vulnerable population. Overall, those requiring hospital admission for treatment administration are potentially exposed to a higher risk of infection and worse outcome given the multiple in-hospital exposures and the treatment immunosuppressive effects.MethodsCOVINT is an observational study assessing COVID-19 incidence among patients receiving anticancer treatment in the outpatient clinic of the Istituto Nazionale dei Tumori di Milano. All consecutive patients with non-haematological malignancies treated with intravenous or subcutaneous/intramuscular anticancer therapy in the outpatient clinic were enrolled. The primary endpoint is the rate of occurrence of COVID-19. Secondary endpoints included the rate of COVID-19-related deaths and treatment interruptions. The association between clinical and biological characteristics and COVID-19 occurrence is also evaluated. COVID-19 diagnosis is defined as (1) certain if confirmed by reverse transcriptase PCR assay of nasopharyngeal swabs (NPS); (2) suspected in case of new symptoms or CT scan evidence of interstitial pneumonia with negative/not performed NPS; (3) negative in case of neither symptoms nor radiological evidence.ResultsIn the first 2 months (16 February–10 April 2020) of observation, 1081 patients were included. Of these, 11 (1%) were confirmed and 73 (6.7%) suspected for COVID-19. No significant differences in terms of cancer and treatment type emerged between the three subgroups. Prophylactic use of myeloid growth factors was adopted in 5.3%, 2.7% and 0% of COVID-19-free, COVID-19-suspected and COVID-19-confirmed patients (p=0.003). Overall, 96 (8.9%) patients delayed treatment as a precaution for the pandemic. Among the 11 confirmed cases, 6 (55%) died of COVID-19 complications, and anticancer treatment was restarted in only one.ConclusionsDuring the pandemic peak, accurate protective measures successfully resulted in low rates of COVID-19 diagnosis, although with high lethality. Prospective patients’ surveillance will continue with NPS and serology testing to provide a more comprehensive epidemiological picture, a biological insight on the impact of cytotoxic treatments on the immune response, and to protect patients and healthcare workers.

Non-clear cell renal cell carcinomas (RCC) comprise several rare and poorly described diseases, often characterized by bad prognosis and with no standard treatments available. The gap in their clinical management is linked to the poor molecular characterization in handling the treatment of non clear-cell RCC with untailored therapies. Due to their rarity, non-clear RCC are in fact under-represented in prospective randomized trials. Thus, treatment choices are based on extrapolating results from clear cell RCC trials, retrospective data, or case reports. Over the last two decades, various options have been considered as the mainstay for the treatment of metastatic RCC (mRCC), including angiogenesis inhibitors, vascular endothelial growth factor receptor inhibitors, other tyrosine kinase inhibitors (TKIs), as well as MET inhibitors and mammalian targeting of rapamycin (mTOR) inhibitors. More recently, the therapeutic armamentarium has been enriched with immunotherapy, alone or in combination with targeted agents that have been shown to significantly improve outcomes of mRCC patients, if compared to TKI single-agent. It has been widely proven that non-clear cell RCC is a morphologically and clinically distinct entity from its clear cell counterpart but more knowledge about its biology is certainly needed. Histology-specific collaborative trials are in fact now emerging to investigate different treatments for non-clear cell RCC. This review summarizes pathogenetic mechanisms of non-clear cell RCC, the evolution of treatment paradigms over the last few decades, with a focus on immunotherapy-based trials, and future potential treatment options.

Background: Desmoid fibromatosis (DF) is a rare and locally infiltrative monoclonal fibroblastic proliferation arising from connective tissues, with lack of metastatic potential. About 10% of all DF cases are intra-abdominally sited. Complications in this site, due to the locally infiltrative nature of the disease, may be severe and potentially life threatening. However, data on incidence, management, and outcome of these complications are limited. Aim: Data of patients with sporadic or FAP-related intra-abdominal DF treated at Istituto Nazionale dei Tumori (INT) in Milano from 2005 to 2020 who developed a serious complication during the course of their disease were retrospectively collected and analyzed with a descriptive statistics. Methods and Results: Out of 72 intra-abdominal DF, 8 cases were identified (M/F: 5/3, median age: 35 years, FAP-related/sporadic: 2/6): 3 with bowel obstruction, 5 with bowel perforation. In 4 cases the serious complication was the first evidence of disease; in the other 4 cases it occurred at a time interval from diagnosis in the range of 4-44 months (during an active surveillance program in one case and duringchemotherapy in the other 3 cases). A surgical treatment was feasible and successful in 5 cases. In 3 surgically unmanageable patients, all progressing and experiencing acute complications while on chemotherapy, a non-surgical approach with intensive supportive treatment and with a prompt change of chemotherapy regimen was implemented, being successful in two, the other patient dying due to a concomitant progressive lymphoma thereafter. Conclusion:In this series of intra-abdominal DF, the incidence of serious complications was 11%. Most patients were successfully treated with surgery. When surgery was deemed to be unfeasible, a conservative management with intensive supportive care and a careful choice of chemotherapy was adopted, ensuring a favorable outcome in most.

In invasive BCs, DCE-MRI voxel-wise enhancement parameters correlated with HER2, pT, and pN.

BackgroundOverexpression of human epidermal growth factor receptor type 2 (HER2) occurs in almost 25-30% of androgen receptor (AR)-positive salivary gland carcinomas (SGCs), notably salivary duct carcinoma (SDC) and adenocarcinoma not otherwise specified (NOS). In the last years, several studies have reported the clinical benefit of HER2 directed therapies in this setting. This work aims at describing the natural history of AR-positive recurrent/metastatic (R/M) SGC patients, based on HER2 amplification status.MethodsConsecutive R/M AR-positive SGC patients accessing our Institution from 2010 to 2021 were analyzed. Descriptive statistics and survival analyses were performed to present the clinical characteristics of the selected patients and the outcomes, based on HER2 status. A specific focus was dedicated to patients developing metastases to the central nervous system (CNS).ResultsSeventy-four R/M AR-positive SGC patients (72 men) were analyzed. Median follow-up was 36.18 months (95% CI 30.19-42.66). HER2 status was available in 62 cases (84%) and in 42% the protein was overexpressed (HER2+). Compared with patients with HER2- SGCs, in patients with HER2+ disease, HR for disease recurrence was 2.97 (95% CI 1.44-6.1, p=0.003), and HR for death from R/M disease was 3.22 (95% CI 1.39-7.49, p=0.007). Moreover, the HER2+ group showed a non-significant trend towards a higher prevalence of CNS metastases (40% vs. 24%, p=0.263). Patients developing CNS metastases had shorter survival than those who did not; at bivariate analysis (covariates: CNS disease and HER2 status), HER2 status demonstrated its independent prognostic significance.DiscussionIn our patient population, HER2 amplification was a negative prognostic factor, and it was associated with a non-statistically significant higher risk of developing CNS metastasis. Further studies are needed to explore the potential clinical benefit of tackling the two biological pathways (AR and HER2) in patients affected by this rare and aggressive malignancy.

4571 Background: Metastatic collecting ducts carcinoma (mCDC) is a rare disease with bad prognosis and no standard treatments. Due to its rarity, mCDC is biologically poorly characterized and under-represented in prospective randomized trials. We recently identified two different molecular subtypes of mCDC based on relative expression levels of angiogenesis, metabolic and immune-related genes. Methods: : This prospective, monocentric, phase II trial evaluated cabozantinib (cabo) 60 mg orally once daily until progression or unacceptable toxicity in untreated mCDC patients (pts). Primary endpoint was objective response rate (ORR) as the proportion of pts with best overall response of confirmed complete (CR) or partial responses (PR) per RECIST 1.1. Secondary endpoints were progression-free survival (PFS), overall survival and safety profile. Exploratory objectives were: to identify somatic mutations by targeted NGS-based sequencing; to define molecular subtypes, signatures and transcript fusions genes by RNA sequencing; to monitor circulating immune cells and study the immunological context of tumor cells. A central pathological review was mandatory. The study was based on a Simon’s two stage optimal design: at least 2 responses in 9 pts in the first stage were needed to proceed to the second stage where at least 6 responses in 14 additional pts were needed to prove activity of cabo. Results: From January 2018 to November 2020, 25 pts were enrolled, of whom 23 started treatment. Median age was 66 years, 19 pts were male. 19 (83%) pts received a previous nephrectomy. 9 pts presented with only one metastatic site, 8 pts with two, while the remaining part with multiple sites. The most common metastatic sites were lymphnodes and bone (15 and 13 pts respectively), followed by lung and liver (10 and 4 pts respectively). Median follow up was 8 months. As best overall response, 6 pts presented a stable disease (26%),1 pt achieved a confimed CR and 7 a PR for an ORR of 35%. Median PFS was 6 months. Treatment was feasible and well tolerated. All pts reported at least one grade (G) 1-2 adverse event (AE): the most common were fatigue (43%), hypotiroidism (28%), stomatitis (28%), anorexia (26%), Hand-Foot Syndrome (13%), hypertension (17%), and diarrhea (13%). 5 pts reported G3 AEs (2 thromboembolic events, 2 arterial hypertension, 1 fatigue), while no G4-5 AEs were reported. 17% of pts required dose reduction. DNA sequencing on CDC showed to be feasible, finding 256 mutations in 119 genes (missens mutations the majority). Altered genes, molecular subtypes and signatures will be associated to different outcomes and responses to cabo. Conclusions: The study met its primary endpoint showing promising efficacy and acceptable tolerability of cabo in mCDC pts. Mature results according to mutational profiles and gene signatures will be presented. Clinical trial information: NCT03354884.

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The dismal prognosis of recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) prompted recent advances in the field of therapeutic approaches beyond cytotoxic cancer therapy. In recent years, the deeper and increasing knowledge on the genomic landscape and the upcoming new data on immunotherapy enacted by HNSCCs have led to successful therapeutic targeting of the immune system. Immune checkpoint inhibitors (ICIs) have changed state of the art in R/M patients and could have a potential role even in early disease. The purpose of this work is to summarize the role of immunotherapy for R/M HNSCC in clinical practice, with insights about future perspectives. Updated immunotherapy results in other R/M head and neck cancers such as thyroid, salivary glands, nasopharynx, sinonasal cancers, and nuclear protein in testis (NUT) are presented.