Pembrolizumab-Induced Isolated Cranial Neuropathy: A Rare Case Report and Review of Literature.

Introduction: Anti-PD1 agents are widely used in the treatment of solid tumors. This has prompted the recognition of a class of immune-related adverse events (irAEs), due to the activation of autoimmune T-cells. Pembrolizumab is an anti-PD1 agent, which has been related to an increased risk of various neurological irAE (n-irAEs). Here, we present a rare case of pembrolizumab-induced neuropathy of cranial nerves. Case Report: A 72-year-old patient was diagnosed with a lung adenocarcinoma in February 2018 (EGFR-, ALK-, and PDL1 90%). According to the molecular profile, pembrolizumab was started. After three administrations, the patient developed facial paresis, ptosis, ophthalmoplegia, and dysphonia. As brain metastases and paraneoplastic markers were excluded, a drug-related disorder was suspected and pembrolizumab was discontinued. A nerve conduction study and electromyography excluded signs of neuropathy and myopathy at four limbs, and repetitive nerve stimulation was negative. However, altered blink reflex and nerve facial conduction were consistent with an acute neuropathy of the cranial district. Thus, the patient was treated with two cycles of intravenous immunoglobulins (IVIg), which rapidly allowed improvement of both symptoms and neurophysiological parameters. However, the patient died in October 2018 for a progression of lung tumor. Discussion: Only 16 cases of pembrolizumab-related neuropathies have been described so far. Our case is of particular interest for the isolated involvement of cranial nerves and the prompt response to IVIg. Conclusion: N-irAEs are insidious conditions that require solid knowledge of onco-immunotherapy complications: it is mandatory not to delay any treatment that would potentially modify the course of a neurological complication.

Role of positron emission tomography-computed tomography in the management of anal cancer.

PURPOSE: Pre- and post-treatment staging of anal cancer are often inaccurate. The role of positron emission tomograpy-computed tomography (PET-CT) in anal cancer is yet to be defined. The aim of the study was to compare PET-CT with CT scan, sentinel node biopsy results of inguinal lymph nodes, and anal biopsy results in staging and in follow-up of anal cancer. METHODS AND MATERIALS: Fifty-three consecutive patients diagnosed with anal cancer underwent PET-CT. Results were compared with computed tomography (CT), performed in 40 patients, and with sentinel node biopsy (SNB) (41 patients) at pretreatment workup. Early follow-up consisted of a digital rectal examination, an anoscopy, a PET-CT scan, and anal biopsies performed at 1 and 3 months after the end of treatment. Data sets were then compared. RESULTS: At pretreatment assessment, anal cancer was identified by PET-CT in 47 patients (88.7%) and by CT in 30 patients (75%). The detection rates rose to 97.9% with PET-CT and to 82.9% with CT (P=.042) when the 5 patients who had undergone surgery prior to this assessment and whose margins were positive at histological examination were censored. Perirectal and/or pelvic nodes were considered metastatic by PET-CT in 14 of 53 patients (26.4%) and by CT in 7 of 40 patients (17.5%). SNB was superior to both PET-CT and CT in detecting inguinal lymph nodes. PET-CT upstaged 37.5% of patients and downstaged 25% of patients. Radiation fields were changed in 12.6% of patients. PET-CT at 3 months was more accurate than PET-CT at 1 month in evaluating outcomes after chemoradiation therapy treatment: sensitivity was 100% vs 66.6%, and specificity was 97.4% vs 92.5%, respectively. Median follow-up was 20.3 months. CONCLUSIONS: In this series, PET-CT detected the primary tumor more often than CT. Staging of perirectal/pelvic or inguinal lymph nodes was better with PET-CT. SNB was more accurate in staging inguinal lymph nodes.

Continuous 5-fluorouracil infusion plus long acting octreotide in advanced well-differentiated neuroendocrine carcinomas. A phase II trial of the Piemonte oncology network.

BACKGROUND: Well-differentiated neuroendocrine carcinomas are highly vascularized and may be sensitive to drugs administered on a metronomic schedule that has shown antiangiogenic properties. A phase II study was designed to test the activity of protracted 5-fluorouracil (5FU) infusion plus long-acting release (LAR) octreotide in patients with neuroendocrine carcinoma. METHODS: Twenty-nine patients with metastatic or locally advanced well-differentiated neuroendocrine carcinoma were treated with protracted 5FU intravenous infusion (200 mg/m2 daily) plus LAR octreotide (20 mg monthly). Patients were followed for toxicity, objective response, symptomatic and biochemical response, time to progression and survival. RESULTS: Assessment by Response Evaluation Criteria in Solid Tumors (RECIST) criteria showed partial response in 7 (24.1%), stable disease in 20 (69.0%), and disease progression in 2 patients. Response did not significantly differ when patients were stratified by primary tumor site and proliferative activity. A biochemical (chromogranin A) response was observed in 12/25 assessable patients (48.0%); symptom relief was obtained in 9/15 symptomatic patients (60.0%). There was non significant decrease in circulating vascular epithelial growth factor (VEGF) over time. Median time to progression was 22.6 months (range, 2.7-68.5); median overall survival was not reached yet. Toxicity was mild and manageable. CONCLUSION: Continuous/metronomic 5FU infusion plus LAR octreotide is well tolerated and shows activity in patients with well-differentiated neuroendocrine carcinoma. The potential synergism between metronomic chemotherapy and antiangiogenic drugs provides a rationale for exploring this association in the future. TRIAL REGISTRATION: NCT00953394.

Oxaliplatin, 5-fluorouracil, and leucovorin as second-line treatment for advanced pancreatic cancer.

OBJECTIVE: A phase II study was performed to assess the activity of oxaliplatin plus 5-fluorouracil (5-FU) modulated by leucovorin, as second-line treatment in locally advanced or metastatic pancreas adenocarcinoma pretreated with gemcitabine-containing schedule. METHODS: Patients received weekly intravenous infusions of oxaliplatin 40 mg/m, 5-FU 500 mg/m, and leucovorin 250 mg/m (3 weeks on, 1 week off). RESULTS: Twenty-three patients affected with metastatic (16) or locally advanced (7) pancreas adenocarcinoma were involved in this study. A total of 148 weeks of chemotherapy was delivered (median 2 courses each patient). Among 17 assessable patients, no objective response was registered and 4 patients had stable disease, whereas 13 had tumor progression. Median duration of stable disease was 14 weeks. Median time to progression of disease (TTP) was 11.6 weeks [95% confidence interval (CI), 7.6-5.6]. Kaplan-Meier estimated median overall survival (OS) was 17.1 week (95% CI, 4.0-30.1) and 3 months survival rate was 69.6%. Seven patients experienced grade 3 to 4 toxicity. The regimen was associated with 36% clinical benefit. CONCLUSIONS: The median TTP and median OS in this population with poor prognosis suggests some activity, however, only further investigations will be able to establish the clinical value of this combination.

Efficacy and skin toxicity management with cetuximab in metastatic colorectal cancer: outcomes from an oncologic/dermatologic cooperation.

PURPOSE: The aim of this study was to investigate the efficacy of the combination of irinotecan/cetuximab and to plan related skin toxicity management with an oncologic/dermatologic team. PATIENTS AND METHODS: Thirty-four patients with epidermal growth factor receptor (EGFR)-expressing metastatic colorectal cancer received cetuximab 400 mg/m2 as an initial dose and 250 mg/m2 weekly thereafter. In addition, patients received irinotecan 180 mg/m2 every 2 weeks. RESULTS: Thirty-two patients were evaluated for response rate (RR) and skin toxicity to establish the best management. In our study, the responses observed with cetuximab treatment were complete response in 1 patient (3%), partial response in 11 patients (34%), disease stabilization in 6 patients (19%), and progressive disease in 14 patients (44%). Of 34 patients evaluable for cutaneous toxicity, 10 patients (29%) presented with grade 1 eruption, 13 (38%) with grade 2 eruption, and 4 (12%) with grade 3 eruption. Allergic reactions such as flushing and urticaria (grade 2) were seen in 2 patients (6%). CONCLUSION: Cutaneous reactions consisted of follicular rash, xerosis, painful fissures in palms and soles, alterations in hair growth, and mucositis. In the majority of patients (80%-90%), the worst recorded skin effects were mild (grade 1) to moderate (grade 2). The incidence of severe cases (grade 3) was approximately 15%. All dermatologic effects were reversible and generally without sequelae within 4 weeks after treatment discontinuation. We observed significant correlations between degree of cutaneous toxicity and increased RR. Correct identification and treatment by oncologic/dermatologic cooperation of EGFR cutaneous side effects help to improve quality of life.