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Background and purpose: Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that enhance the immune response against cancer cells. ICIs are generally well tolerated, although endocrine immune-related adverse events (irAEs) are common. We investigated the risk factors for thyroid irAEs in patients treated with ICIs. Moreover, we evaluated the clinical outcome of subjects who became hypothyroid compared to euthyroid patients. Patients and methods: We retrospectively analyzed a series of 195 consecutively subjects treated with ICIs for metastatic tumors at the University of Naples “Federico II” between January 2014 and March 2020. Only subjects tested for thyroid function before and during the treatment with ICIs were included. Results: In the 96 patients treated with ICIs who were included [66 males, median age: 62 years (27–87)], thyroid irAEs occurred in 36 (37.5%), 16 (16.7%) a transient thyrotoxicosis, and 20 (20.8%) an hypothyroidism (in nine subjects hypothyroidism was preceded by a transient thyrotoxicosis). Only baseline TSH levels above 1.67 mIU/L and positive anti-thyroid antibodies (Ab-T) were associated with a higher risk of hypothyroidism. Patients with hypothyroidism during ICI treatment showed an improved 2-year PFS (HR = 0.82 CI 0.47–1.43; p= 0.0132) and OS (HR = 0.38 CI 95% 0.17–0.80; p= 0.011) compared to euthyroid patients. Conclusions: Baseline TSH levels above 1.67 mIU/L and presence of Ab-T are risk factors for the development of thyroid irAEs. Patients affected by thyroid irAEs showed a longer survival than patients who remained euthyroid.

Paraneoplastic sensitive neuropathy is one of the most common presentations among a group of cancer-related disorders known as Paraneoplastic Neurological Syndromes (PNS). PNS likely have an autoimmune etiology since they have been associated with the presence of antibodies against neuronal antigens expressed by tumor cells (such as anti-Hu, anti-Ri and anti-Yo). The tumors most frequently associated with PSN and onconeural antibodies are lung cancer, lymphomas and gynaecological tumors; however, they have also been described in other tumors. We report, for the first time, a case of neuroendocrine tumor of duodenum and PNS associated with anti-Hu antibodies. Moreover, we analyze and discuss the clinical implications that PNS and anti-Hu could have in patients with tumors.

CEA, TPA, CA 15-3 were assayed in 238 patients in follow-up for breast cancer after surgery. CA 15-3 showed the best sensitivity and specificity; the predictive value of a positive CA 15-3 test was three times higher than CEA and TPA. No association was found between marker positivity and the number of organs involved by metastases. CA 15-3 positivity was significantly associated with visceral rather than soft tissue recurrences; no significant similar association was observed for CEA and TPA. CA 15-3 serum levels were early predictors of relapse in four out of nine patients within a 6-12 month follow-up period.

Forty-five patients with stage III-IV low grade non-Hodgkin's lymphoma (NHL) were treated with a non-intensive polychemotherapy regimen including chlorambucil-vincristine and cytarabine (Ara-C), termed COA, for a total of 366 courses, beginning in June 1986. Grade 4 myelotoxicity occurred in only 4/45 patients. No treatment related death was observed. All patients were evaluable for response. Overall, 38 (84%) objective responses, including 31 (69%) complete responses (CR), were observed. At a median follow-up of 57 (21-84+) months, only 8 deaths occurred. Twenty-seven (60%) patients are still disease-free. All disease-free patients were in their first CR. The seven-year estimated survival is 71% and the estimated 7-year progression-free survival (PFS) was 48%. The estimated probability of complete responders to be disease-free at 6 years is 78%. Pretreatment laboratory parameters (serum levels of thymidine kinase, LDH and TNF-alpha showed a good prognostic relevance at using univariate analysis. At multivariate analysis, only the pretreatment serum levels of TNF-alpha were significantly associated with a higher CR achievement probability (p = 0.02) and a longer PFS (p = 0.02). We established a risk model for clinical outcome based on these 3 parameters. Patients having all parameters within the normal range at diagnosis, showed a very good prognosis (100% 7-year PFS and survival), while patients with all parameters increased had a very poor prognosis (0% 7-year PFS and 22% 7-year survival). In conclusion, COA treatment appears to be a non-toxic and very effective treatment for low-grade non-Hodgkin's lymphomas. More intensive treatment is probably needed for patients showing multiple negative prognostic laboratory parameters at diagnosis.

The prognostic role of drug-induced amenorrhea (DIA) was restrospectively evaluated in 221 out of 254 consecutive premenopausal patients treated with adjuvant CMF or a CMF-containing regimen; 33 patients were eliminated because of lack of menstrual data. All patients had metastatic axillary nodes; drug regimens were: CMF x 9 courses +/- Tamoxifen (TM) and CMF x 6 courses; median age was 43 (range 26-54). Premenopausal status was defined as last normal menses within the 6 weeks preceding initiation of chemotherapy: DIA as cessation of menses for at least 3 months not later than 3 months from the end of chemotherapy. DIA occurred in 166,221 (75.1%) patients and was strictly related to the age of the patients; also, the older the patients the shorter the time required to develop DIA. At median follow up of 69 months, Mantel-Byar analysis showed a longer disease free survival (DFS) for patients who developed DIA as compared with non amenorrheic women (P less than 0.001). DIA prognostic value was independent of age, number of involved nodes, tumour size and number of CMF cycles, as assessed by the Cox model (RH 0.43, 95% C.I. 0.24-0.77), in which DIA was entered as a time dependent covariate.