Long-term therapy with Bevacizumab in a young patient affected by NF2. Stop or continue treatment? An update of a case report and review of the literature.

Neurofibromatosis type 2 (NF2) is an autosomal dominant condition caused by pathogenic variants in the NF2 gene. To date, cytotoxic chemotherapy has no established role in the treatment of NF-2. Historical case reports of malignant schwannomas have documented responses to chemotherapies with cyclophosphamide, vincristine and doxorubicin, in patients who develop pulmonary metastases. Recently, several studies proposed the use of anti-HER2, anti-EGFR, anti-platelet-derived growth factor receptors. As reported in our previous review of the literature, vascular endothelial growth factor (VEGF) and its receptor VEGFR-1 have been detected in schwannomas with the best results. We described the case of a young patient with NF2 treated for long time with Bevacizumab. Here, we report the update of the previous case report.

Late immune-related adverse events in long-term responders to PD-1/PD-L1 checkpoint inhibitors: A multicentre study.

BACKGROUND: Data on spectrum and grade of immune-related adverse events (irAEs) in long-term responders to immune checkpoint inhibitors (ICIs) are lacking. METHODS: We performed a retrospective multicenter study to characterized irAEs occurring after a 12-months minimum treatment period with PD-(L)1 ICIs in patients with advanced cancer. IrAEs were categorized into 'early' (≤12 months) and 'late' (>12 months). RESULTS: From September 2013 to October 2019, 436 consecutive patients were evaluated. Two hundred twenty-three experienced any grade early-irAEs (51.1%), whereas 132 experienced any grade late-irAEs (30.3%) (p < 0.0001). Among the latter, 29 (22%) experienced a recurrence of an early-irAEs, whereas 103 (78%) experienced de novo late-irAEs involving different system/organ. Among patients with late-irAEs, 21 experienced GIII/GIV irAEs (4.8%). Median time to onset of early-irAEs was 3.4 months (95% confidence interval [CI]: 2.8-4.2), whereas the median time to onset of late-irAEs was 16.6 months (95% CI: 15.8-17.6). Cumulative time-adjusted risk of disease progression according to both the early-irAEs (hazard ratio [HR] = 0.63 [95% CI: 0.30-1.29], p = 0.204) and late-irAEs occurrence revealed no statistically significant differences (HR = 0.75 [95% CI: 0.37-1.56], p = 0.452). In addition, the time-adjusted cumulative risk of death in accordance with both early-irAEs (HR = 0.79 [95% CI: 0.34-1.86], p = 0.598) and late-irAEs (HR = 0.92 [95% CI: 0.49-1.74], p = 0.811) did not show statistically significant differences. CONCLUSION: Although less frequent than early-irAEs, late-irAEs are quite common in long responders to PD-(L)1 ICIs and are different in terms of spectrum and grade. Time-adjusted analysis revealed that the cumulative risk of disease progression and death were not significantly reduced in patients who experienced late-irAEs.

Cyclin-dependent kinase inhibitors plus aromatase inhibitor in first-line treatment hormone-receptor-positive/HER2-negative advanced breast cancer women with or without visceral disease: time to turn page?

Breast cancer is the most common female tumour type and accounts for the leading cancer mortality in women worldwide. Up to 75% of breast cancers express the oestrogen receptor or progesterone receptor (hormone-receptor-positive). Aromatase inhibitors were the preferred first-line treatment option. New and acquired resistance to hormonal blockade has led to the development of targeted treatments. Cyclin-dependent kinases (CDKs) are a large family of serine-threonine kinases that play an important role in regulating cell cycle progression: palbociclib, ribociclib, and abemaciclib. We conducted a study to evaluate the efficacy of CDK inhibitors (CDKi) plus aromatase inhibitor in hormone-receptor-positive/HER2-negative ABC patients with visceral disease, postponing the use of chemotherapeutic agents and strengthening the power of endocrine agents. We enrolled 22 patients treated with CDKi (palbocilib) plus aromatase inhibitor (group A) and 38 patients treated with chemotherapy (group B). Our small study confirms the effectiveness of treatment with CDKi plus aromatase inhibitor, even in patients with visceral metastases, when compared with chemotherapy.

On-target Toxicities Predictive of Survival in Metastatic Renal Cell Carcinoma (mRCC) Treated With Sunitinib: A Multicenter Retrospective Study.

BACKGROUND: Preliminary studies suggested that selected drug-related toxicities of sunitinib may correlate with a better prognosis. PATIENTS AND METHODS: From January 2006 through December 2015, we retrospectively analyzed data of 145 patients with metastatic renal cell carcinoma treated with sunitinib as a first-line therapy in 7 different Italian oncology departments. Hypertension, hypothyroidism, thrombocytopenia, neutropenia, and anemia were evaluated. Overall survival (OS) and progression-free survival (PFS) were calculated. OS and PFS were compared in patients who developed and who did not develop a drug-related toxicity. A multivariate analysis using the Cox regression model was performed. RESULTS: We evaluated 145 patients (92 males; median age, 70 years); 105 (62.4%) patients experienced at least 1 toxicity: 66 (45.5%) patients developed hypothyroidism, 41 (28.3%) thrombocytopenia, 39 (26.9%) hypertension that required medical therapy, 22 (15.2%) anemia, and 11 (7.6%) neutropenia. The median PFS of patients who developed hypertension was 12 months (95% confidence interval [CI], 9-21 months) versus 9 months (95% CI, 7-12 months) in patients who did not develop toxicity; the median OS was 36 months (95% CI, 22 months to not reached) versus 26 months (95% CI, 18-34 months). For neutropenia, the median PFS was 17.5 months (95% CI, 9-65 months) versus 10 months (95% CI, 8-12 months); the median OS was 23 months (95% CI, 13 months to not reached) versus 28 months (95% CI, 22-35 months). At univariate and multivariate analysis, we observed a protective effect of hypertension and neutropenia on tumor progression (hazard ratio, 0.47; 95% CI, 0.28-0.78 and hazard ratio, 0.26; 95% CI, 0.09-0.76, respectively). CONCLUSIONS: Many patients developed toxicities during treatment with sunitinib; hypertension and neutropenia were related to longer PFS in our cohort.

Biological effects of verbascoside and its anti-inflammatory activity on oral mucositis: a review of the literature.

Oral mucositis is among the most common tissue toxicities associated with both cytotoxic cancer regimens and head and neck radiotherapy. Current management of oral mucositis might comprise growth factors and cytokines, anti-inflammatory agents, anesthetics, analgesics, antimicrobial and coating agents, cryotherapy and mucosal protectants. Despite its long history and its impact on patients, there are currently no effective options for the prevention or treatment of mucositis. In recent years, more attention has been focused on the role of natural drugs. Verbascoside belongs to the phenylpropanoid glycosides family. Several biological properties have been described, such as anti-inflammatory, antimicrobial, antitumor and antioxidant. Verbascoside, particularly when in solution with polyvinylpyrrolidone and sodium hyaluronate, thanks to barrier effect, is useful in re-epithelialization and in reducing pain, oral mucositis score, burning and erythema.

Poorly Differentiated Neuroendocrine Carcinoma of the Sigmoid Tract in Long-Standing Ulcerative Colitis: Report of a Case and Review of the Literature.

A 37-year-old male with long-standing and extensive ulcerative pancolitis developed a rapidly lethal poorly differentiated neuroendocrine carcinoma (NEC) in the sigmoid colon. Prior biopsies obtained from multiple sites of the colon during endoscopic surveillance showed minimal inflammatory changes and no sign of dysplasia. Patients with inflammatory bowel disease (IBD) are at increased risk of colorectal malignancies, and adenocarcinoma is the most common type of colorectal neoplasm associated with ulcerative colitis and Crohn's disease, but other types of epithelial and nonepithelial tumors have also been described in IBD. NECs arising in the setting of ulcerative colitis are very rare and are reported as anecdotic findings. We describe the clinicopathological features of an IBD-related NEC and review the previously reported cases.

Biopsy and re-biopsy in lung cancer: the oncologist requests and the role of endobronchial ultrasounds transbronchial needle aspiration.

As the leading cause of death worldwide, lung cancer has proven itself incurable in the advanced stages. For early stages, endobronchial ultrasounds transbronchial needle aspiration (EBUS-TBNA) is now considered the standard to assess mediastinal lymph node, to define the multimodality therapeutic approach. In recent years, EBUS-TBNA has extended its use also in the metastatic and locally recurrent disease. New molecules, with specific mutations that give resistance to current target therapies, have made re-biopsy at disease progression an important assessment, with therapeutic and clinical implication. Here we present the oncologist's point of view on EBUS-TBNA in the staging process, at recurrence and progression.