Long-term disease control in a metastatic squamous cell carcinoma of the oral cavity treated with maintenance metronomic capecitabine.

Recurrent or metastatic disease occurs in two-thirds of head and neck squamous cell carcinomas and it is associated with poor prognosis. Systemic treatment with platinum-based chemotherapy in combination with the epidermal growth factor receptor-targeting monoclonal antibody cetuximab represents a preferred option for these patients. Upon the achievement of tumor response by combined treatment, maintenance with single-agent cetuximab is usually administered with the aim of prolonging disease control at the price of reasonable toxicity. Although rarely, however, cetuximab needs to be discontinued in the absence of disease progression because of intolerable side effects. Here we describe the case of a 66-year-old man with a metastatic cancer of oral cavity, who had to discontinue maintenance cetuximab and who achieved prolonged disease control with metronomic capecitabine. We suggest that capecitabine could be an effective and safe maintenance option in case of cetuximab intolerance.

Long-term disease control and high clinical benefit in a patient with advanced thyroid cancer treated with lenvatinib.

We report a case of a 37-year-old man with metastatic differentiated thyroid carcinoma, previously submitted to total thyroidectomy, radio-iodine therapy and lung metastasectomy, who underwent systemic treatment with lenvatinib for tumor recurrence in the lung, mediastinal lymph nodes, left gluteus and left orbit. Lenvatinib induced rapid and durable disease regression; the drug effect has continued after >1 year, as well as a very considerable clinical benefit. The results achieved by lenvatinib in treatment of metastatic differentiated thyroid carcinoma are clear and irrefutable. Real-life data, obtained by case reports and retrospective studies, are equally important to increase the knowledge about this drug and improve the clinical management.

Luteinized thecoma (thecomatosis) with sclerosing peritonitis: a systematic review of the literature of the last 25 years.

INTRODUCTION: Luteinized thecoma (thecomatosis) with sclerosing peritonitis (LTSP) is a very uncommon syndrome, characterized by the presence of single or bilateral ovarian thecomas and peritoneal fibrotic lesions. The disease occurs in young women and it can lead to peritoneal fibrosis and bowel obstruction. The pathogenesis of this syndrome remains still largely unknown. Surgery represents the cornerstone of treatment, but resection alone does not always allow a complete disease control. Attempts at medical treatments have been reported in recent years, but a real standard therapy has not yet been defined. AREAS COVERED: We performed a systematic review of literature, collecting all the papers that reported cases of LTSP, since its first description in 1994. We found that, in these 25 years, less than 50 cases have been described in literature. EXPERT OPINION: Along with the established role of surgery, adjuvant treatment with hormonal agents, in particular in estrogen receptor expression, seems to be a promising approach. However, more efforts must be carried out to describe treatment and outcome of new cases, improving knowledge about this rare condition.

Discrepancy between tumor response and hematologic response in a patient with thymoma and aplastic anemia treated with ciclosporin.

Pure red cell aplasia (PRCA) represents one of the most common paraneoplastic syndromes in patients with advanced thymoma. Ciclosporin is a very effective treatment in this condition, and it seems to have also a direct anti-cancer effect. We provide a case of radiological response of thymoma associated with the total absence of response of PRCA in a patient treated with ciclosporin. A 60-year-old man with advanced thymoma underwent first-line chemotherapy, achieving a partial disease response followed by 2 years of stable disease. After disease progression, the patient developed a PRCA, later expanded to platelets, and then he started therapy with ciclosporin, without any blood improvement. The CT revaluation after three months of ciclosporin therapy showed tumor shrinkage, although the inefficacy in the treatment of PRCA. The paper reports a case of dissociation between oncological and hematological response in a patient with thymoma-related PRCA, suggesting that the pathology of this condition deserves novel investigations. Further studies should be conducted to acquire more exhaustive knowledge and permit the integrated treatment of oncological and hematological conditions.

Systemic recurrence of endometrial cancer more than 10 years after hysterectomy: a report of two cases and a brief review of the literature.

BACKGROUND: Endometrial carcinoma is one of the most common female cancers in developed countries. Disease stage is associated with the risk of disease relapse after radical treatment. Typically, the risk of disease relapse peaks at 3 years from local radical treatment and then diminishes over time, so that late relapses (i.e., from year 5 afterward) are extremely infrequent. Here, we report two cases of women with endometrial cancer who developed a disease relapse more than 15 years after radical treatment. A review of the literature revealed other seven reports of women with relapse from endometrial cancer occurring more than 10 years after radical treatment. CASE PRESENTATION: Case report 1 is a 56-year-old woman with an endometrioid cancer who underwent a hysterectomy with bilateral salpingo-oophorectomy in 1998. She relapsed in the lung in 2014, 16 years from radical surgery. Case report 2, a 75-year-old woman, with an endometrioid cancer, was treated by hysterectomy with bilateral salpingo-oophorectomy and adjuvant radiotherapy. The disease relapse in the lung was detected in 2019, 22 years from radical treatment. CONCLUSION: Although guidelines do not support oncological follow-up beyond 5 years from surgery, oncologists should consider late recurrence of endometrial carcinoma in the differential diagnosis of women presenting with metastases of uncertain origin and prior history of this disease.

Ocular metastases from neuroendocrine tumors: A literature review.

Background Neuroendocrine tumors (NETs) include malignancies with different origins, clinical presentations and prognosis. Synchronous or metachronous ocular metastases from NET are extremely rare. The diagnostic algorithm and the management of this entity has not been established. The aim of our study was to characterize this subgroup. Methods We performed an electronic search in PubMed Library databases for articles about ocular metastases from NET published from 1966 to August 2019. Results We identified 21 manuscripts with a total of 64 cases. The primary origin of the tumor was lung in 28 (43.7%) cases, ileum in 14, unknown in 8, colon in 3, rectum, esophagus, thymus, testicle and liver in 1 case each, and not reported in 6. The histopathological confirmation of NET metastasis was available in 25 cases (39%). The most common sites of intraocular lesions was the uvea in 30 (46.8%) cases, followed by the orbit in 27. Most of the patients (n = 44, 68.7%) presented eye symptoms. Locoregional interventions were performed in 40 patients (62.5%): 15 cases underwent surgery, 19 had external beam radiotherapy, 5 had brachytherapy, and 1 patient received laser photocoagulation. These treatments ensured the local control in 28 of the 40 (70%) cases treated with a locoregional approach. Conclusions Ocular metastases from NETs are exceptionally rare, and originate more frequently from foregut primary tumors (lung, esophageal, and thymic NETs). The most common ocular site of secondary lesions is the uvea, likely due to its high vascularization. Locoregional approaches appear to be effective in terms of local disease control.

Prolonged Adrenal Insufficiency After the Discontinuation of Mitotane Therapy.

INTRODUCTION: Adrenocortical carcinoma (ACC) is a rare neoplasm characterized by a high risk of recurrence after radical resection. The role of adjuvant systemic therapy in radically resected patients is unclear. Mitotane, a steroidogenesis inhibitor, is the only drug approved for the systemic treatment of advanced ACC. In 2007, a retrospective case-control study provided the evidence that mitotane, administered for two years after successful surgery, could prolong recurrence-free survival. Adrenal insufficiency (AI), which occurs in almost all patients during the first 12 months of treatment, is an expected side effect of mitotane and requires steroid replacement therapy. Due to its long halflife, mitotane-induced AI persists several months after treatment discontinuation and is managed by cautious tapering of glucocorticoid replacement therapy. RESULTS: We report a case of symptomatic AI diagnosed after a severe allergic reaction occurring three years after the discontinuation of adjuvant mitotane therapy. CONCLUSION: The case suggests that mitotane-induced AI should be monitored for a long time to asses full recovery of adrenal function, in order to prevent adrenal crises.

Quality of life assessment and reporting in colorectal cancer: A systematic review of phase III trials published between 2012 and 2018.

BACKGROUND: In this study, our aim was to describe quality of life (QoL) prevalence and heterogeneity in QoL reporting in colorectal cancer phase III trials. METHODS: We included all phase III trials evaluating anticancer drugs in colorectal cancer patients published between 2012 and 2018 by 11 major journals. RESULTS: Out of the 67 publications identified, in 41 (61.2 %) QoL was not listed among endpoints. Out of 26 primary publications of trials including QoL among endpoints, QoL results were not reported in 10 (38.5 %). Overall, no QoL data were available in 51/67 (76.1 %) primary publications. In particular, in the metastatic setting, QoL data were not available in 12/18 (66.7 %) trials with primary endpoint overall survival, and in 20/29 (69.0 %) trials with other primary endpoints. CONCLUSIONS: QoL was absent in a high proportion of recently published phase III trials in colorectal cancer, even in trials of second or further lines, where attention to QoL should be particularly high.

Quality of life analysis in lung cancer: A systematic review of phase III trials published between 2012 and 2018.

OBJECTIVES: We previously reported that quality of life (QoL) is not included among trial endpoints and QoL results are underreported in a significant proportion of phase III oncology trials. Here we describe QoL adoption, reporting and methodology of QoL analysis in lung cancer trials. MATERIALS AND METHODS: We selected all primary publications of lung cancer phase III trials assessing anticancer drugs published between 2012 and 2018 by 11 major journals. RESULTS: 122 publications were included. In 39 (32.0%) publications, QoL was not listed among endpoints: in 10/17 (58.8%) early stage/locally advanced NSCLC, in 15/54 (27.8%) first-line of advanced NSCLC; in 10/41 (24.4%) second and further lines of advanced NSCLC, in 4/10 (40.0%) SCLC. Proportion of trials not including QoL was similar over time: 32.9% publications in 2012-2015 vs. 30.6% in 2016-2018. Out of 83 trials including QoL among endpoints, QoL results were absent in 36 primary publications (43.4%). Proportion of trials without QoL results in primary publication increased over time (30.6% 2012-2015 vs. 61.8% 2016-2018, p = 0.005). Overall, QoL data were not available in 75/122 (61.5%) primary publications, due to the absent endpoint or unpublished results. QoL data were lacking in 48/68 (70.6%) publications of trials with overall survival as primary endpoint, 27/54 (50.0%) with other primary endpoints and 28/54 (51.9%) publications with a positive result. For trials including QoL among endpoints but lacking QoL results in primary publication, probability of secondary publication was 6.3%, 30.1% and 49.8% after 1, 2 and 3 years respectively, without evidence of improvement comparing 2012-2015 vs. 2016-2018. CONCLUSION: QoL is not assessed or published in many phase III lung cancer trials, a setting where QoL value should be highly considered, due to high symptom burden and generally limited life expectancy. Timely inclusion of results in primary publications is worsening in recent years.

Target therapies in recurrent or metastatic head and neck cancer: state of the art and novel perspectives. A systematic review.

Recurrent or metastatic head and neck squamous-cell carcinomas (R/M HNSCC) are a group of cancers with a very poor prognosis. Many clinical trials testing novel target therapies in this setting are currently ongoing. We performed a systematic review focusing our attention on all clinical trials, ongoing or already published, concerning the use of novel drugs for treatment of R/M HNSCC. We found that the research of novel molecules effective in treatment of R/M HNSCC has been intense during last decade, and nowadays it is still very active. Unfortunately, the results in this setting have been, overall, disappointing: until now, only cetuximab and, recently, nivolumab and pembrolizumab received authorization for treatment of R/M HNSCC. Nevertheless, the promising results showed by some novel drugs may lead to continue the research in this field, with the aim of producing more evidence and finding new therapeutic indication.

Capecitabine plus temozolomide in well- or moderately-differentiated primary atypical neuroendocrine tumours - single-centre experience of two cases.

INTRODUCTION: Neuroendocrine neoplasms (NENs) are a rare and heterogeneous group of tumours, with a variety of primary origins and variable aggressiveness. NENs with an atypical primary origin, such as breast and retroperitoneal NENs, are extremely rare. As a consequence, an established diagnostic and therapeutic strategy in this particular subgroup is lacking. The combination of capecitabine and temozolomide, called CAPTEM regimen, has produced promising response rates in patients with grade 1 or 2 neuroendocrine tumours of multiple origins. CASE PRESENTATION: The first is a case of a 68-year-old woman with a metastatic primary breast neuroendocrine tumour, treated with cisplatin plus etoposide as first line, followed by CAV scheme (cyclophosphamide, doxorubicin, and vincristine), and subsequently treated, in third line with the CAPTEM regimen, obtaining radiological response and good tolerance. The second is the case of a 66-year-old woman affected by a metastatic primitive retroperitoneal NET G2. The patient progressed after a somatostatin analogue-based first line, whereas the CAPTEM regimen led to a partial and durable response with a favourable safety profile. CONCLUSIONS: CAPTEM chemotherapy has been shown to be an active and safe therapeutic option in advanced, metastatic G1/2 atypical primary NENs.

Quality-of-Life Assessment and Reporting in Prostate Cancer: Systematic Review of Phase 3 Trials Testing Anticancer Drugs Published Between 2012 and 2018.

Quality of life (QoL) is not included among the end points in many studies, and QoL results are underreported in many phase 3 oncology trials. We performed a systematic review to describe QoL prevalence and heterogeneity in QoL reporting in recently published prostate cancer phase 3 trials. A PubMed search was performed to identify primary publications of randomized phase 3 trials testing anticancer drugs in prostate cancer, issued between 2012 and 2018. We analyzed QoL inclusion among end points, presence of QoL results, and methodology of QoL analysis. Seventy-two publications were identified (15 early-stage, 20 advanced hormone-sensitive, and 37 castration-resistant prostate cancer [CRPC]). QoL was not listed among study end points in 23 studies (31.9%) (40.0% early stage, 40.0% advanced hormone sensitive, and 24.3% CRPC). QoL results were absent in 15 (30.6%) of 49 primary publications of trials that included QoL among end points. Overall, as a result of absent end point or unpublished results, QoL data were lacking in 38 (52.8%) primary publications (53.3% early stage, 55.0% in advanced hormone sensitive, and 51.4% in CRPC). The most commonly used QoL tools were Functional Assessment of Cancer Therapy-Prostate (FACT-P) (21, 53.8%) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) (14, 35.9%); most common methods of analysis were mean changes or mean scores (28, 71.8%), time to deterioration (14, 35.9%), and proportion of patients with response (10, 25.6%). In conclusion, QoL data are lacking in a not negligible proportion of recently published phase 3 trials in prostate cancer, although the presence of QoL results is better in positive trials, especially in CRPC. The methodology of QoL analysis is heterogeneous for type of instruments, analysis, and presentation of results.

hERG1 positivity and Glut-1 negativity identifies high-risk TNM stage I and II colorectal cancer patients, regardless of adjuvant chemotherapy.

BACKGROUND: The identification of early-stage colorectal cancer (CRC) with high risk of progression is one major clinical challenge, mainly due to lack of validated biomarkers. The aims of the present study were to analyze the prognostic impact of three molecular markers belonging to the ion channels and transporters family: the ether-à-go-go-related gene 1 (hERG1) and the calcium-activated KCa3.1 potassium channels, as well as the glucose transporter 1 (Glut-1); and to define the impact of adjuvant chemotherapy in conjunction with the abovementioned biomarkers, in a cohort of radically resected stage I-III CRC patients. PATIENTS AND METHODS: The expressions of hERG1, KCa3.1, and Glut-1 were tested by immunohistochemistry on 162 surgical samples of nonmetastatic, stage I-III CRC patients. The median follow-up was 32 months. The association between biological markers, clinicopathological features, and survival outcomes was investigated by evaluating both disease-free survival and overall survival. RESULTS: Although no prognostic valence emerged for KCa3.1, evidence of a negative impact of hERG1 expression on survival outcomes was provided. On the contrary, Glut-1 expression had a positive impact. According to the results of the multivariate analysis, patients were stratified in four risk groups, based on TNM stage and hERG1/Glut-1 expression. After adjusting for adjuvant therapy, stage I and II, Glut-1-negative, and hERG1-positive patients showed the worst survival experience. CONCLUSION: This study strongly indicates that the combination of hERG1 positivity and Glut-1 negativity behaves as a prognostic biomarker in radically resected CRC patients. This combination identifies a group of stage I and II CRC patients with a bad prognosis, even worse than that of stage III patients, regardless of adjuvant therapy accomplishment.