In recent years, cancer research has highlighted the role of disrupted microbiota in carcinogenesis and cancer recurrence. However, microbiota may also interfere with drug metabolism, influencing the efficacy of cancer drugs, especially immunotherapy, and modulating the onset of adverse events. Intestinal micro-organisms can be altered by external factors, such as use of antibiotics, proton pump inhibitors treatment, lifestyle and the use of prebiotics or probiotics. The aim of our review is to provide a picture of the current evidence about preclinical and clinical data of the role of gut and local microbiota in malignancies and its potential clinical role in cancer treatments. Standardization of microbiota sequencing approaches and its modulating strategies within prospective clinical trials could be intriguing for two aims: first, to provide novel potential biomarkers both for early cancer detection and for therapeutic effectiveness; second, to propose personalized and "microbiota-tailored" treatment strategies.

CDKi are standard of care for patients (pts) with advanced hormone-positive (HR+) BC, with recent results even in the adjuvant setting. Nevertheless, management and clinical implication of hepatotoxicity during CDKi are not well described in literature, even if it is reported in a non-negligible rate within trials. A multicenter Italian retrospective study was conducted in 2023, collecting and pooling data of pts affected by HR+ HER2- BC, treated with CDKi and aromatase inhibitors (AI) or fulvestrant (FULV). This study aims to describe the incidence and the management of liver adverse events (AEs) during CDKi in a real-world setting. A descriptive analysis was performed as pivotal evaluation for designing an observational study. 256 pts were included across 5 centres: 96% of pts received CDKi in the metastatic setting. Pts were treated with ribociclib (42%), abemaciclib (25%) and palbociclib (33%) associated with AI or FULV. Liver AEs occurred in 16% of pts, with a median time of onset of 90 days. 19 pts (46%) experienced grade ≥3 (G≥3) liver AEs: mostly with elevated liver enzymes (95%). No acute liver failure was reported. The rate of liver AEs was 20% for ribociclib, 17% for abemaciclib and 11% for palbociclib. Ribociclib and abemaciclib were associated with 79% and 21% of G≥3 liver AEs. Diagnostic assessments were performed in 37% of pts with liver AEs: hepatotropic viruses screening (68%), autoimmunity screening (28%) and radiological exams (4%). Only one liver biopsy was performed with a diagnosis of drug induced liver injury. Recovery of normal liver function after CDKi discontinuation was achieved in 68% of pts, with a median time of 30 days. After resolution of G≥3 liver AEs, 26% of pts discontinued any treatment, 5% continued only AI or FULV, 48% resumed CDKi with dose reduction and 21% shifted to another CDKi without any further G≥3 liver AEs. In our cohort the incidence of liver AEs was significant, with a relevant number of G≥3 AEs. Since hepatotoxicity is defined by diagnosis of exclusion, a prompt screening for differential causes is crucial in case of abnormal liver function. After non serious liver AEs, resumption of lower dose or shift to another CDKi may be a safe therapeutic option.

Limited real-world data exists on treatment patterns and outcomes in R/M HNC pts receiving anti-PD-1 immunotherapy (IT). This study provides insights into contemporary IT use and sequencing. Preliminary results from five centers in four European countries (Italy, Poland, Portugal, Slovenia) are presented. A retrospective federated analysis of R/M HNC pts who received IT between March 2017 and May 2022 was conducted. Data were analyzed at each center using a common R script. Overall survival (OS) and real-world progression-free survival (rwPFS) were calculated from IT start. Lines of systemic therapy (line) included concomitant chemotherapy (ChT) used with radiotherapy (CRT). A total of 224 pts with a median age of 58–67 yrs across countries were included. 43.8% of pts had metastatic disease as opposed to locoregional only at IT start, 64.7% had platinum refractory disease, and 19.2% were tested for PD-L1 expression. 9.8% of pts began their treatment with IT, whereas most pts. received anti-PD-1 after previous CRT or as a 2nd line (pembrolizumab 10.0%, pembrolizumab+ChT 4.4%, nivolumab 85.6%). In the first line, the most common systemic treatments beside platinum-based CRT (39.3%) were platinum-containing combination ChT without cetuximab (37.5%) and ChT+cetuximab (12.0%). The maximum number of lines in any patient was 10 and nivolumab was the most used agent overall (25.6%) followed by non-platinum monochemotherapy (21.4.%). Median overall survival from anti-PD-1 initiation across countries was 5.9–13.6 months (ms), and the median rwPFS ranged from 2.8–4.8 ms. The overall occurrence of irAEs ranged from 18.3–81.3% across countries, with the most common irAEs being gastrointestinal (25.8%) and endocrinal disorders (17.9%). There were 57.3% grade 2, 6.6% grade 3 and no grade 4 or 5 irAEs. This real-world study across four European countries shows variable IT utilization and outcomes, irAEs occurrence, and treatment patterns in R/M HNC. Further research is needed to optimize IT use, considering pts characteristics and treatment-related factors.

PDF file, 30KB, ERCC1 gene expression under mitotane treatment in ACC cancer cells.

Although adrenocortical carcinoma (ACC) during pregnancy is rare, a retrospective review of a case series at our hospital revealed that almost one third of our patients were women in childbearing age. Given that the age of maternity is increasing, dealing with a tumor diagnosis during pregnancy and the need for fertility planning in cancer survivors is likely to become more frequent.We thus carried out a case-based discussion regarding: i) diagnosing and treating an ACC during pregnancy; ii) patients conceiving while on mitotane; iii) ACC survivors with a maternal desire.In each of these cases, it is important to provide patients with sufficient information, to offer medical advice and psychological support, to personalize treatments in accordance with the wishes of the patient and her relatives, and to collaborate with other specialists since a multidisciplinary expert team is required to manage each case individually.

This study investigated the clinical management of non small cell lung cancer (NSCLC) patients during the first wave of coronavirus disease 2019 (COVID-19) outbreak in Italy. A 29-questions survey was sent to 95 Italian thoracic oncologists, with 77 % of them declaring significant changes in the outpatients management and treatment. The results of this survey pointed out a significant delay of lung cancer diagnosis along with a relevant reduction of patients' accrual within clinical trials. Telemedicine emerged as a valid support for patient-healthcare interactions. Therapeutic indications followed the guidelines for adjuvant chemotherapy and concurrent chemo-radiation. Clinical indications to first-line therapies were largely confirmed, while major changes regarded the selection of second line treatment options as well as the management of elderly population. This work may represent a valid source of information to improve the clinical management of NSCLC patients during second wave of COVID-19 pandemic.

Background: The world, and Italy on the front lines, has experienced a major medical emergency due to the novel coronavirus outbreak. Cancer patients are one of the potentially most vulnerable cohorts of people, but data about their management are still few. Patients and Methods: In this monocentric retrospective study we included all SARS-CoV-2 oncological patients accepted, between March 27th and April 19th 2020, at the Onco-COVID Unit at San Luigi Gonzaga Hospital, one of the few Italian oncological-COVID wards. Data were obtained from medical records. Results: Eighteen cancer patients with COVID-19 were included. The mean (±SD) age of patients was 67 ± 14 years, 89% were men. Seven (39%) developed infection in communities and 11 (61%) during hospitalization. Lung cancer was the most frequent type of cancer (10, 56%). Seven patients (39%) were symptomatic for COVID-19 at the time of diagnosis and symptoms began 2 (±2) days before. The most common were shortness of breath and diarrhea. Fever was present in 5 patients (28%). Among the 11 asymptomatic patients, 8 (73%) became symptomatic during the hospitalization (mean time of symptoms onset 4 days ±4). Six patients (33%) were on active anti-tumor treatment: 2 (33%) received anti-tumor therapy within 2 weeks before the infection diagnosis and 2 (33%) continued oncological treatment after SARS-CoV-2 positivity. Eight (44%) patients died within a mean of 12 days (±8) from the infection diagnosis. Conclusions: Our series confirms the high mortality among cancer patients with COVID-19. The presence of asymptomatic cases evidences that typical symptoms and fever are not the only parameters to suspect the infection. The Onco-Covid unit suggests the importance of a tailored and holistic approach, even in this difficult situation.

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.

Background: At the end of 2019, a novel viral pneumonia, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was described in China Since then, Italy has soon become one of the most affected countries In this challenging situation, the oncological community was called to protect cancer patients (pts), especially those affected by lung cancer, considered one of the most vulnerable population due to older age, multiple comorbidities and type of infection This study aimed to investigate the clinical management of NSCLC pts, in order to provide a reliable picture of real-word practice during the COVID-19 outbreak Materials and Methods: A 29-questions survey focusing on the clinical management and therapeutic indications for NSCLC pts during COVID-19 pandemic was sent to 95 medical/thoracic oncologists across different Italian regions Results: From April 12th to May 2nd, 79 responses were received, with an overall response rate of 83% The majority (77 3%) of oncologists declared a significant change in the outpatient management of NSCLC pts The number of consultations in case of suspected NSCLC decreased in about half of cases (46 8%), with a major reduction when considering the number of pts coming from the emergency department for a first oncological evaluation (60% of cases) The total number of pts with any stage, newly diagnosed NSCLC, within the observational period, was reported to be lower than the pre-pandemic era by the 56% of oncologists For pts candidates to adjuvant chemotherapy and concurrent chemoradiation, the therapeutic indications followed guidelines in 62% and 72% of cases, respectively As regards the metastatic disease, the majority of oncologists confirmed their clinical indication to first-line treatment The collected data revealed major changes in the second line therapeutic options, most related to timing and schedules of administration Lung cancer pts' accrual in clinical trials dramatically has fallen for 79% of oncologists and follow-up consultations were mostly managed by telemedicine Conclusions: This survey showed that Italian oncologists are determined to follow the available guidelines for the clinical management of NSCLC pts during this emergency time, while more complicate is to deal with clinical trials In this tough landscape, telemedicine provides a valid support to facilitate patient-healthcare interactions

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.

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.

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.

Background: At the end of 2019, a novel viral pneumonia, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was described in China Since then, Italy has soon become one of the most affected countries In this challenging situation, the oncological community was called to protect cancer patients (pts), especially those affected by lung cancer, considered one of the most vulnerable population due to older age, multiple comorbidities and type of infection This study aimed to investigate the clinical management of NSCLC pts, in order to provide a reliable picture of real-word practice during the COVID-19 outbreak Materials and Methods: A 29-questions survey focusing on the clinical management and therapeutic indications for NSCLC pts during COVID-19 pandemic was sent to 95 medical/thoracic oncologists across different Italian regions Results: From April 12th to May 2nd, 79 responses were received, with an overall response rate of 83% The majority (77 3%) of oncologists declared a significant change in the outpatient management of NSCLC pts The number of consultations in case of suspected NSCLC decreased in about half of cases (46 8%), with a major reduction when considering the number of pts coming from the emergency department for a first oncological evaluation (60% of cases) The total number of pts with any stage, newly diagnosed NSCLC, within the observational period, was reported to be lower than the pre-pandemic era by the 56% of oncologists For pts candidates to adjuvant chemotherapy and concurrent chemoradiation, the therapeutic indications followed guidelines in 62% and 72% of cases, respectively As regards the metastatic disease, the majority of oncologists confirmed their clinical indication to first-line treatment The collected data revealed major changes in the second line therapeutic options, most related to timing and schedules of administration Lung cancer pts\u0027 accrual in clinical trials dramatically has fallen for 79% of oncologists and follow-up consultations were mostly managed by telemedicine Conclusions: This survey showed that Italian oncologists are determined to follow the available guidelines for the clinical management of NSCLC pts during this emergency time, while more complicate is to deal with clinical trials In this tough landscape, telemedicine provides a valid support to facilitate patient-healthcare interactions

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.

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.

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.

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.

Background: Luteinized thecoma with sclerosing peritonitis (LTSP) is a very rare condition, and its clinical management is not evidence-based. Here we describe a case of long-term disease control achieved with leuprorelin and tamoxifen therapy. Case presentation: A 18-year-old woman with acute abdomen underwent surgical removal of an ovarian mass and received diagnosis of LTSP. Treatment plan consisted of leuprorelin and tamoxifen, followed by a good instrumental response. After 5 years, leuprorelin was stopped, and the patient continued tamoxifen alone. Ten years after diagnosis, she is still disease free. Conclusion: Even in the absence of solid evidence, the combination of leuprorelin and tamoxifen could be considered as a possible medical treatment of LTSP. Considering the limitations related to the rarity of disease, further studies are needed to improve its management.

Topoisomerase II alpha (TOP2A) and thymidylate synthase (TS) are known prognostic parameters in several tumors and also predictors of efficacy of anthracyclines, topoisomerase inhibitors and fluoropirimidines, respectively. Expression of TOP2A and TS mRNA was assessed in 98 patients with adrenocortical carcinoma (ACC) and protein expression was assessed by immunohistochemistry in a subset of 39 tumors. Ninety-two patients were radically resected for stage II-III disease and 38 of them received adjuvant mitotane. Twenty-six patients with metastatic disease received the EDP-M (etoposide, doxorubicin, Adriamycin, cisplatin plus mitotane). TOP2A and TS expression in ACC tissue was directly correlated with the clinical data. Both markers were not associated with either disease free survival (DFS) or overall survival (OS) in multivariate analyses and failed to be associated to mitotane efficacy. Disease response or stabilization to EDP-M treatment was observed in 12/17 (71%) and 1/9 (11%) patients with high and low TOP2A expressing tumors (P = 0.0039) and 9/13 (69%) and 4/13 (31%) patients with high and low TS expressing ACC, respectively (P = 0.049). High TOP2A expression was significantly associated with longer time to progression (TTP) after EDP-M. TOP2A and TS proteins assessed by immunohistochemistry significantly correlated with mRNA expression. Immunohistochemical TOP2A expression was associated with a non-significant better response and longer TTP after EDP-M. TOP2A and TS were neither prognostic nor predictive of mitotane efficacy in ACC patients. The predictive role of TOP2A expression of EDP-M activity suggests a significant contribution of Adriamycin and etoposide for the efficacy of the EDP scheme.

Topoisomerase II alpha (TOP2A) and Thymidylate Synthase (TS) are known prognostic parameters in several tumors. They are also predictors of efficacy of anthracyclines and topoisomerase inhibitors and fluoropirimidines, respectively. The prognostic and predictive role of tumor tissue mRNA expression of TOP2A and TS was assessed in 98 patients with adrenocortical carcinoma (ACC). Ninety-two were radically resected for stage II-III disease and 38 of them received adjuvant mitotane after surgery. Twenty-six patients with metastatic disease at first diagnosis or at the time of recurrence after surgery received the EDP-M (Etoposide, Doxorubicin=Adriamycin, Cisplatin plus mitotane). TOP2A and TS expression in ACC tissue was directly correlated. Both markers were not associated with either disease free survival (DFS) after surgery or overall survival (OS) in multivariate analyses and failed to be associated to mitotane efficacy in terms of DFS. A clinical benefit (disease response or disease stabilization) to EDP-M treatment was observed in 12/17 (71%) and 1/9 (11%) patients with high and low TOP2A expressing tumors (p=0.0039) and 9/13 (69%) and 4/13 (31%) patients with high and low TS expressing ACC, respectively (p=0.049). High TOP2A expression was significantly associated with longer time to progression after EDP-M. TOP2A and TS were neither prognostic nor predictive of mitotane efficacy in ACC patients. The predictive role of TOP2A expression of EDP-M activity suggests a significant contribution of adriamycin and etoposide for the efficacy of the EDP scheme.