A single experience in the conduction of clinical trial during COronaVIrusDisease-2019 pandemic.

Aim: From the start of the pandemic, several aspects of healthcare policies changed, not least the clinical trials management from recruiting capabilities to the protocol compliance in terms of schedule of procedures, follow-up visits, staff constraints and monitoring. This study aims to assess the impact of the COronaVIrusDisease-2019 (COVID-19) pandemic in the conduction of clinical trials at the site of clinical oncology, Ancona (Italy), to identify the strengths and weaknesses upfront the past emergency, and to select better strategies for future similar situations. Methods: Data from February to July of the years 2019, 2020 and 2021 were collected and three practical parameters of the trial unit were investigated: milestones, performance, and impact. Results: The trials mean numbers were 18, 24, and 23, in 2019, 2020, and 2021 respectively. The pre-Site Initiation Visit (PRE-SIV) rate grew from 66.6% in 2019 to 95.5% in 2021 with a deflection in 2020. Protocol deviations were 40 in the period February-July 2019, in the same period of 2020 the number of deviations increased due to COVID related ones, then there was a significant total decrease in February-July 2021. In 2020 and 2021, all the investigator meetings were online. Conclusions: The growing number of remote Site Initiation Visit (SIV) and meetings over the last 3 years suggests the feasibility of the on-line processes. The significant reduction in protocol deviations during 2021 is probably due to an under check of data during a pandemic. But that is also a possible key indicator of the coping strategy made out by clinical oncology to guarantee the continuity of care in clinical trials and to offer new opportunities of cancer care in a bad scenario such as a pandemic one.

Impact of coronavirus disease 2019 pandemic on good clinical practice trials in oncology.

Aim: Coronavirus disease 2019 (COVID-19) became pandemic on 11th March 2020 and it deeply stressed the healthcare system. Cancer patients represent a vulnerable population, so many recommendations have been approved to ensure optimal management. Clinical research was notably impacted by COVID too. This review aims to analyze the challenges occurred during a pandemic for the management of enrolled patients (enrollment, use of telemedicine visits, study procedures) and for the clinical trials system (from feasibility to selection visit, site initiation visit, monitorings, use of e-signature, deviations and discontinuations). Methods: The studies included in the present review were selected from PubMed/Google Scholar/ScienceDirect databases. Results: During the first phase of pandemic many clinical trials were suspended in accrual and, as the pandemic progressed, recommendations were established to guarantee the safety and the continuity of care of enrolled patients. In addition, lot of new strategies was found during the pandemic to reduce the negative consequences on clinical trial performance and to guarantee new opportunities of care in the respect of good clinical practice (GCP) in a bad scenario. Conclusions: Among all modifiers, investigators would prefer to maintain the positive ones such as pragmatic and simplified trial designs and protocols, reducing in-person visits when not necessary and to minimizing sponsor and contract research organizations (CROs) visits.

Gender Differences and Outcomes in Melanoma Patients.

INTRODUCTION: Melanoma is one of the most common cancers in younger people. The incidence of cutaneous melanoma is increasing in patients of both sexes, with female patients generally living longer than their male counterparts. The aim of this retrospective study was to evaluate and confirm the sex-based difference in survival of melanoma patients and the relationship of this difference with pathological features. METHODS: A total of 1023 patients who had been treated at the Department of Medical Oncology, Università Politecnica Marche (Ancona, Italy) and the INRCA-IRCCS Department of Dermatology (Ancona, Italy) between 1987 and 2014 were enrolled in the study. RESULTS: In terms of stage of disease at onset, there was a significant difference in disease-free survival (DFS) and overall survival (OS) in favor of female patients in disease stage I (P = 0.001 and P = 0.01, respectively) and II (P = 0.02 and P = 0.009, respectively). Female patients also showed a significant improvement in 12-year DFS and 12-year OS adjusted for pathological features (Breslow thickness, ulceration, "absent" tumor-infiltrating lymphocyte (TIL) melanomas, "non-brisk" TIL pattern). Globally, female patients had an advantage over with male patients in both DFS and OS (P < 0.001). CONCLUSIONS: Our results show that women have a survival benefit over with men after adjustment for many variables that can reduce mortality risk in female melanoma patients. In a future investigation we wish to examine possible biological sex differences in tumor-host interactions.

Hyponatremia is a Predictor of Clinical Outcome for Resected Biliary Tract Cancers: A Retrospective Single-Center Study.

INTRODUCTION: Biliary tract cancers (BTC) include both gallbladder cancer and cholangiocarcinoma, both of which have a poor prognosis. The aim of our study was to evaluate the main clinical prognostic factors in this setting and to assess their impact on overall survival (OS). METHODS: We retrospectively analyzed data collected on 64 patients with BTC who underwent surgery with radical intent at our institution. OS was estimated using the Kaplan-Meier method. The Cox regression model was used to perform univariate and multivariate analyses. RESULTS: Preoperative hyponatremia was found to be an independent prognostic factor that correlated negatively with prognosis, with hyponatremic patients having a poor OS compared to the group of patients with normal serum sodium levels (9.44 vs. 15.47 months; p = 0.0215). In addition, high preoperative values for carbohydrate antigen 19-9 (Ca19.9), a tumor marker for some gastrointestinal cancers, and lactate dehydrogenase (LDH) were found to be prognostic factors for a significant reduction in OS (Ca19-9: 7.14 vs. 24.22 months, p = 0.0088; LDH: 1.70 vs. 15.47 months, p = 0.0384). CONCLUSION: Identification of these prognostic factors may support strategies to identify, in clinical practice, those subgroups of patients with a favorable or unfavorable prognosis before surgical treatment and, therefore, to guide therapeutic choices. In particular, to our knowledge, this is the first report of the prognostic role of serum sodium level in BTC. Early detection and careful monitoring of hyponatremia and supportive therapy can help to improve the treatment and prognosis of BTC.

Long-responders to anti-HER2 therapies: A case report and review of the literature.

Since the introduction of targeted therapies, prognosis in human epidermal growth factor receptor (HER) 2-positive metastatic breast cancer (MBC) has radically changed. The addition of Pertuzumab to Trastuzumab and standard chemotherapy has further increased patients' overall survival (OS). However, there is no agreement regarding the optimal duration of trastuzumab therapy in selected patients achieving long-term complete remission. In addition, no potential factors of long-term benefit have been identified yet. In the present study, we report the case of a MBC woman who was successfully treated with trastuzumab for over 10 years. At the time of diagnosis (February 2005), she revealed lung, nodal and bone metastases. Therefore, a first-line chemotherapy with Epirubicine and Docetaxel was administered for 6 cycles and then the patient started Trastuzumab plus hormonal therapy until reaching a sensible reduction of mammary lump and disappearance of distant metastases. Following a multidisciplinary evaluation, in November 2006, the patient underwent radical mastectomy and axillary dissection, achieving a complete remission. She continued Trastuzumab until September 2015 (for a total of 156 cycles) when a pleural diffusion was demonstrated. Long-term survival during anti-HER2 treatment remains a rare and optimal situation. Currently, no data exist to support trastuzumab interruption in this setting and collaborative efforts to better analyze the characteristics of long-responder patients are needed. Data regarding prognostic factors in this setting are relatively confusing. Our review reveals that hormonal receptor (HR)-positive disease is associated with a better prognosis, whereas the role of visceral spread differs by single or dual target anti HER2-inhibition. The introduction of Pertuzumab is raising concerns in terms of toxicity and its cost effectiveness. While waiting for novel molecular data and randomized trials, available evidence advocates continuous use of anti-HER2 therapies until disease progression or development of side effects.

Compliance with breast and cervical cancer screening programs in women: results from a population-based study.

AIMS AND BACKGROUND: Women's adherence to mammography and PAP test screening guidelines is a fundamental topic regarding women's health. The aim of the study was to evaluate the knowledge and compliance to breast and cervical cancer screening programs in women living in three Italian towns, where a public screening program, consisting of free mammography every two years and free PAP test every three years, is ongoing. METHODS: An anonymous survey was mailed to a random sample of women. Eight 120-min focus discussions with groups of women exploring perceptions, knowledge and practices were carried out after analysis of the returned surveys. RESULTS: Replies were received from 1345 women (response rate, 27%). Almost every woman knew of the screening program, but women's practice of mammography was age-dependent: up to 72% of the women performed it before the age of 50. Conversely, the age of the first PAP test was rather late: up to 70% of the women performed it at over 30 years of age. Women with a lower educational level reported being screened less than those with a higher level. During the group discussions, women's perceptions, knowledge and beliefs regarding cancer and screening, together with aspects of the health care system, appeared to strongly influence the preventive practices. Many women deplored being infrequently instructed by health professionals. CONCLUSIONS: Despite the limitations of the study due to the low response rate, we believe that health professionals should invest on encouraging factors and reduce the deterring factors to optimize screening practices.