Alpelisib for PIK3CA-mutated advanced gynecological cancers: First clues of clinical activity.

OBJECTIVE: Recurrent gynecological tumors (e.g., endometrial, and ovarian cancers) are incurable diseases; therefore, new treatment options are urgently needed. The PTEN-AKT-PI3K pathway is frequently altered in these tumors, representing a potential treatment target. Alpelisib is an α-specific PI3K inhibitor approved in PIK3CA-mutated advanced breast cancer. We report outcomes from a large series of patients with PIK3CA-mutated gynecological cancers prospectively treated with alpelisib within a controlled program. METHODS: From April 2021 to December 2022, 36 patients with PIK3CA-mutated advanced gynecological cancers received alpelisib 300 mg orally once daily. Objective response (ORR) and disease control (DCR) rates provided measure of the antitumor activity of alpelisib, the primary objective of the study. RESULTS: Included patients had endometrial (17/36 [47%]), ovarian (10/36 [28%]), or other gynecological cancers (9/36 [25%]). Most patients had received 2-3 prior systemic treatments (endometrial, 47·2%; ovarian, 60%; other, 56%), and presented with visceral metastases at baseline (82%, 70%, and 56%, respectively). Overall, 17 different PIK3CA mutations were found, including 53% in the kinase domain (most commonly H1047R) and 36% in the helical domain (most commonly E545K). Overall, the ORR was 28% and DCR was 61%, with the greatest benefit observed in patients with endometrial cancer (35% and 71%, respectively). CONCLUSION: Alpelisib represents an active treatment option in patients with recurrent gynecological cancers harboring a PIK3CA mutation. These findings support the need of biomarker-driven randomized trials of PI3K inhibitors in gynecological cancers.

Chemotherapy-induced neurotoxicity in the treatment of gynecological cancers: State of art and an innovative approach for prevention.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect that occurs in 20% of ovarian cancer patients treated with the combination of carboplatin/paclitaxel (CP). This toxicity is directly correlated with the dose of paclitaxel administered. Several studies have investigated whether different formulations of taxane can induce this side effect at a lower rate, but, unfortunately, no significant improvement was obtained. CIPN can be disabling in the daily lives of patients and can cause dose reduction or early termination of the treatment. Neuropathy can last for months and even years after its onset. Moreover, patients responsive to CP treatment are candidates for a reintroduction of the same drugs when disease relapse occurs, and residual neuropathy can affect the continuation of treatment. There are no approved drugs that mitigate or prevent the onset of CIPN. In this review, we summarize the evidence regarding the incidence of CIPN with different taxane formulations, regimen schedules and prevention systems. In particular, the Hilotherm® Chemo care device is a regional cooling system that lowers the temperature of the hands and feet to reduce the flow of chemotherapy into the capillaries. We used hilotherapy during chemotherapy infusion to prevent the onset of CIPN. Updated data from 44 ovarian cancer patients treated with 6 cycle of CP show that hilotherapy was well tolerated; only two patients (4.5%) stopped hilotherapy because of cold intolerance, and only one patient (2.2%) experienced grade ≥ 2 CIPN.

Differential Diagnosis of Small Cell Carcinoma of the Ovary or Ovarian Metastases of Small Cell Carcinoma of the Lung: A Case Report and Review of the Literature.

Small cell tumors arise from the neuroendocrine cell system and they are most frequently found in the lung (SCLC). Small cell tumor could occasionally arise in other body sites, such as the cervix, prostate, gastrointestinal tract, and very rarely from other sites. Metastatic SCLC patients present with metastatic disease in 80% of cases, and the metastases typically are reported in brain, liver, lung, and bone; they rarely could be found in the ovary. Differently, primitive small cell carcinoma of the ovary of pulmonary type is a rare and highly aggressive tumor arising from the ovarian cells; no suitable treatment strategy has been established yet. In this paper, we talk about a 72-year-old woman who presented with abdominal bleeding and a large mass in her pelvic region. A primary ovarian carcinoma was suspected, and she underwent hysterectomy with laparoscopic surgery and bilateral oophorectomy, lymph node resection, omentectomy, complementary appendix and sigmoid resection. The postoperative pathologic diagnosis was a differential diagnosis between small cell ovarian carcinoma of the pulmonary type and metastasis of SCLC.

Use of Antibiotics and Risk of Cancer: A Systematic Review and Meta-Analysis of Observational Studies.

The association between antibiotic use and risk of cancer development is unclear, and clinical trials are lacking. We performed a systematic review and meta-analysis of observational studies to assess the association between antibiotic use and risk of cancer. PubMed, the Cochrane Library and EMBASE were searched from inception to 24 February 2019 for studies reporting antibiotic use and subsequent risk of cancer. We included observational studies of adult subjects with previous exposure to antibiotics and available information on incident cancer diagnoses. For each of the eligible studies, data were collected by three reviewers. Risk of cancer was pooled to provide an adjusted odds ratio (OR) with a 95% confidence interval (CI). The primary outcome was the risk of developing cancer in ever versus non-antibiotic users. Cancer risk's association with antibiotic intake was evaluated among 7,947,270 participants (n = 25 studies). Overall, antibiotic use was an independent risk factor for cancer occurrence (OR 1.18, 95%CI 1.12-1.24, p < 0.001). The risk was especially increased for lung cancer (OR 1.29, 95%CI 1.03-1.61, p = 0.02), lymphomas (OR 1.31, 95%CI 1.13-1.51, p < 0.001), pancreatic cancer (OR 1.28, 95%CI 1.04-1.57, p = 0.019), renal cell carcinoma (OR 1.28, 95%CI 1.1-1.5, p = 0.001), and multiple myeloma (OR 1.36, 95%CI 1.18-1.56, p < 0.001). There is moderate evidence that excessive or prolonged use of antibiotics during a person's life is associated with slight increased risk of various cancers. The message is potentially important for public health policies because minimizing improper antibiotic use within a program of antibiotic stewardship could also reduce cancer incidence.

Yoga Protocol for Cancer Patients: A Systematic Exploration of Psychophysiological Benefits.

BACKGROUND: Several studies report that practicing Yoga may lead to numerous psychophysiological benefits in patients undergoing treatment for cancer. Moreover, it may result in an effective alternative for coping with sleep disturbances, anxiety, depression and fatigue symptoms. A study based on the "Yoga in Oncology" project of the Foundation Poliambulanza was carried out, and it was designed to explore the benefits of Yoga, therefore corroborating Yoga as a therapeutic activity that can have a beneficial impact on patients diagnosed with cancer. METHODS: Seventy patients were recruited, of whom 20% were males and 80% were females 18 years of age and older. All patients were being treated at the oncology department for gastrointestinal, mammary or genital carcinoma, and the disease was metastatic in 80% of patients. Data were collected between April 2013 and May 2017. The protocol consisted of a weekly 90-minute Yoga lesson for 8 consecutive weeks, and the data collection was carried out in 2 phases: (T0) preprotocol assessment and (T1) postprotocol assessment. Psychophysiological assessment was carried out with the following scales: the (BFI) Brief Fatigue Inventory, (HADS) Hospital Anxiety and Depression Scale and (PSQI) Pittsburgh Sleep Quality Index. RESULTS: Data analysis showed a significant difference between the (T0) and (T1) HADS (Hospital Anxiety and Depression Scale) scores. The constructs of this scale consist of psychological variables for the assessment of anxiety and depression. In contrast, scores from the (BFI) Brief Fatigue Inventory and (PSQI) Pittsburgh Sleep Quality Index did not show significant differences between (T0) and (T1): such scales are relative to psychophysiological variables for an assessment of the perception of fatigue and quality of sleep. CONCLUSION: It is noteworthy that the data, once analyzed, showed a significant difference between preprotocol and postprotocol levels of anxiety and depression but not for the perception of fatigue or the quality of sleep. In accordance with the scientific literature, data from this study highlight that practicing Yoga may promote changes in the levels of perceived anxiety and depression in patients undergoing treatment for cancer, thus positively affecting their (QoL). It is clear that the difference in significance between the psychological and physiological variables considered here and the statistical significance found only in levels of anxiety and depression encourage further studies to account for the nature of fatigue and sleep disturbances and how to address these symptoms in oncological patients. Moreover, other points of interest for future clinical research regard the evaluation of the reason for the possible denial to participate to this kind of study, as well as the social-cultural differences in patients' behavior.

Impact of a Psycho-Educational Team in early Breast Cancer Patients' Coping Strategies: The Venere Project.

AIMS AND BACKGROUND: The main purpose of our psycho-educational groups was to help women with breast cancer, learn how to cope with the physical, emotional, and lifestyle changes associated with cancer as well as with medical treatments that can be painful and traumatic. With this study, we wanted to detect the effects that group action had on the women who participated in it. METHODS: We studied a total of 97 patients who participated in 13 psycho-education groups. The whole sample was female patients who had breast cancer with no recurrence or metastases. RESULTS: All patients were evaluated with the Hospital Anxiety and Depression Scale (HADS) and the Body Image Scale (BIS). We found no significant effect on anxiety and body image for the brief psycho- educational group for women with breast cancer in this study. It is possible to highlight a statistical difference and hence an improvement between the results of the HADS depression test at T0 (first evaluation at the first meeting) and T1 (retest in the final meeting). CONCLUSION: The tests did not show a significant effect on anxiety and body image perception, but the patients reported that the psycho-educational group was an important intervention for their life. Outcome measurement is more complex in psychosocial research because many variables come into play and each phase of treatment is characterized by different types of problems for the patient: physical, relational and psychological aspects are involved.

Parents with cancer: Searching for the right balance between telling the truth and protecting children.

OBJECTIVE: Recent scientific approaches to cancer patients draw attention to the psychological aspects of the disease and the involvement of their families, who are forced to reorganize themselves in order to manage the patient's illness. Functional responses to a stressful event facilitate open communication between family members and empathy for the patient's children, who need to be involved and informed about the illness in a clear and open fashion. The primary goal of this observational study was to explore the communication styles used by cancer-stricken parents with their children and to identify a correlation with the patient's levels of anxiety and depression and their ability to cope. We also sought to understand whether location, severity, and time from diagnosis influenced communication, coping, anxiety, or depression. METHOD: From September of 2011 to July of 2015, 151 questionnaires were given to patients who had received at least one course of chemotherapy. The instruments that we employed were the Openness to Discuss Cancer in the Nuclear Family Scale, the Hospital Anxiety and Depression Scale, and the Mini-Mental Adjustment to Cancer Scale. Our sample included patients with children aged from 3 to 18 years. The patients had different types of cancer, mainly gastrointestinal and breast cancer. Their disease was at the metastatic stage in approximately 20% of patients. RESULTS: Our results showed statistically significant correlations between higher levels of anxiety and depression and more closed communication styles. The coping styles "hopelessness/helplessness," "cognitive avoidance," and "anxious preoccupation" were associated with a closed communication style that is correlated with higher levels of anxiety and depression. Tumor location, time from diagnosis, and stage of disease did not show statistically significant correlations with anxiety, depression, coping mechanisms, or communication styles. SIGNIFICANCE OF RESULTS: Our study confirmed what has been reported in the literature: high levels of anxiety and depression affect communication among family members. Not surprisingly, the "fighting spirit" coping style engenders open communication.

Gemcitabine Plus Nab-Paclitaxel as Second-Line and Beyond Treatment for Metastatic Pancreatic Cancer: a Single Institution Retrospective Analysis.

Metastatic pancreatic cancer still represent one of the most deadly disease for which there are few therapeutic options, especially in second line and beyond setting. Nabpaclitaxel plus gemcitabine activity was demonstrated in first line setting, but there are no clear evidence suggesting its use after that. We report a retrospective data analysis of 23 patients who received nab-paclitaxel plus gemcitabine after first line treatment at our Oncology Department. We observed a significant clinical benefit (43,5%) with a median overall survival of 5 months. In addition, manageable side effects were reported. Our data, despite the small sample, seem to indicate that nab- paclitaxel plus gemcitabine is an active and well tolerated regimen even in pretreated patients.

Assessing cancer caregivers' needs for an early targeted psychosocial support project: The experience of the oncology department of the Poliambulanza Foundation.

OBJECTIVE: Caregivers play a key role in the management of patients with cancer. However, some studies have suggested that caregivers have even more unmet needs than the patients. METHOD: To better identify the needs and changes in the lifestyles of the caregivers in our practice and to plan a targeted support project to decrease caregiver burden, we administered the Caregiver's QoL Index-Cancer (CQoLC) to 200 consecutive caregivers. This questionnaire assesses psychological well-being, the relationship with healthcare professionals, administration of finances, lifestyle disruption, and positive adaptation. RESULTS: Our data showed that being a caregiver to a patient with metastatic disease negatively affected females mostly with regard to mental and emotional burden, while men complained more about their sexual life (42.3 vs. 33.6%), although this result was not significant. Some 93.5% of caregivers reported that they were pleased with their role, while 83.4% were concerned about financial difficulties. SIGNIFICANCE OF RESULTS: We strongly believe that early supportive care directed not only at patients but also to caregivers may improve the quality of life (QoL) in this population. We are currently developing a targeted support project to decrease caregiver burden.

Thyroid carcinoma showing thymus-like differentiation: Case presentation of a young man.

Ectopic thymic tissue can be present in the thyroid gland and a carcinoma showing thymus-like differentiation (CASTLE) may arise from such tissue. We are reported the case of a 26-year-old man with CASTLE, with cervical subcutaneous nodules relapse, who showed a good response to treatment with surgery, chemotherapy and radiotherapy. The problematic aspect of this case was the diagnosis; only on review were we able to make a final diagnosis. CASTLE is a very rare neoplasm. It is important to differentiate this cancer from others tumors such as primary or metastatic squamous cell carcinoma of the head and neck or squamous cell thyroid carcinoma, because the therapy and prognosis are different. Diagnosis is complicated and requires careful histological analysis (CD5- and P63-positive with presence of Hassall's corpuscles); unfortunately there is no gold standard treatment so, in this case, we administered a sandwich of chemotherapy and radiotherapy.

Tyrosine Kinase Inhibitors in EGFR-Mutated Large-Cell Neuroendocrine Carcinoma of the Lung? A Case Report.

Large-cell neuroendocrine carcinoma (LCNEC) of the lung is a high-grade carcinoma belonging to the neuroendocrine tumors of the lung and is different from typical lung large-cell carcinoma. It represents about 3% of all pulmonary malignancies and is characterized by neuroendocrine cytologic features. The treatment usually is platinum-based chemotherapy, however the outcome remains poor. Therefore new therapeutic options are needed. Tyrosine kinase inhibitors have demonstrated greater efficacy and better tolerability than standard chemotherapy in non-small-cell lung cancer harboring epidermal growth factor receptor (EGFR) mutations. EGFR gene mutations were also rarely identified in LCNEC. We report a patient with lung LCNEC activating EGFR mutations who showed an impressive response to gefitinib.

Correlation among Streptococcus bovis, endocarditis and septicemia in a patient with advanced colon cancer: a case report.

INTRODUCTION: One of the bacterial agents that has been found to be associated with colorectal cancer is Streptococcus bovis, with 13% of infective endocarditis cases caused by this pathogenic species. CASE PRESENTATION: We describe the case of a 57-year-old Caucasian man with infiltrating and ulcerating metastatic adenocarcinoma of the sigmoid colon. The patient was receiving second-line chemotherapy treatment and, on the eighth day of the second cycle, he developed a grade IV pancytopenia. We diagnosed a severe sepsis with positive blood cultures for Streptococcus bovis/gallolyticus with a secondary endocarditis. CONCLUSIONS: A recent study suggests that the majority of patients affected by colonic cancer have a Streptococcus bovis/gallolyticus colonization that becomes apparent as an overt infection only when immunosystem disorders or cardiac valve lesions occur. This correlation is important for involving more specialists in a correct and early diagnosis of this rare, but potentially fatal, complication.

Targeting VEGF-VEGFR Pathway by Sunitinib in Peripheral Primitive Neuroectodermal Tumor, Paraganglioma and Epithelioid Hemangioendothelioma: Three Case Reports.

Sunitinib malate (Sutent(TM); Pfizer Inc., New York, N.Y., USA) is a small molecule kinase inhibitor with activity against a number of tyrosine kinase receptors, including vascular endothelial growth factor receptors, stem-cell factor receptor, and platelet-derived growth factor receptors alpha and beta. Sunitinib, registered for the treatment of renal cell carcinoma and gastrointestinal stromal tumors, has recently been approved for the treatment of patients with advanced pancreatic neuroendocrine tumors. Peripheral primitive neuroectodermal tumor (pPNET), paraganglioma (PGL) and epithelioid hemangioendothelioma (EHE) are rare tumors in which there is an overexpression of pro-angiogenic factors and in which a high intratumoral microvessel density is a significant poor prognostic factor. On the basis of this preclinical rationale and the lack of effective treatments in pre-treated advanced stages of these rare diseases, we report our interesting experience of pPNET, PGL and EHE treatment with sunitinib.

Lack of a chemobrain effect for adjuvant FOLFOX chemotherapy in colon cancer patients. A pilot study.

PURPOSE: Chemotherapy improves the survival rate of stage III colon cancer patients. The combination of oxaliplatin, 5-fluorouracil, and leucovorin (the FOLFOX4 regimen) has emerged as the standard of care. This prospective study evaluates potential alterations in cognitive function in FOLFOX4-treated patients. METHODS: We evaluated 57 consecutive colorectal cancer patients who received adjuvant chemotherapy with FOLFOX4. Patients underwent a complete battery of neuropsychological tests at three different times: before (T0), at the end (T1), and 6 months after treatment (T2). RESULTS: We have analyzed cognitive impairment (Mini Mental State Examination, MMSE), visuo-spatial memory (Clock Drawing Test, CDT, Rey Complex Figure, copy and recall), information processing speed (Trial Making Test-A, TMT-A, and Trial Making Test-B, TMT-B), verbal memory (Rey Auditory Verbal Learning Test, call and recall), emotional distress (Psychological Distress Inventory, PDI), anxiety (State and Trait Anxiety Inventory, STAI-Y1 and Y2), and depression (Beck Depression Inventory, BDI). Then we have calculated, for each test and for each interval of time, mean ± standard deviation for the mean. In a subsequent phase, we tested the significance of different results through the ANOVA analysis for repeated measures. In this case, we could not find any statistically significant modification in cognitive function, but we could notice an improvement in emotional performance, anxiety and depression a short time after chemotherapy administration. CONCLUSIONS: We found no effect on cognitive function related to chemotherapy, the only little modification is about some emotional performance during chemotherapy. These findings may be explained by the central role of the psychological adaptation process, which occurs during the period from diagnosis to completion of treatment and is characterized by anxiety and adjustment depression. Our results seem to rule out any significant cognitive impairment due to adjuvant FOLFOX4 chemotherapy in colon cancer patients.

Oxaliplatin-induced lung toxicity. Case report and review of the literature.

Rapidly developing pulmonary fibrosis associated with the use of the anti-cancer drug oxaliplatin has been reported mainly by Asiatic literature as isolate case reports. This rare but potentially fatal side effect has neither identified risk factors nor established treatment guideline. We report here a new clinical case concerning a patient with advanced gastric cancer treated with the oxaliplatin-based FOLFOX regimen along with a review of the literature as well as a discussion of emerging experimental treatment mainly based on imatinib.