Drug-Related Pneumonitis in Cancer Treatment during the COVID-19 Era.

Interstitial lung disease is recognized as a group of diseases with a different etiopathogenesis characterized by chronic lung inflammation with the accumulation of inflammatory cells, lymphocytes and macrophages, and the consequent release of proinflammatory cytokines. Various degrees of pulmonary fibrosis can be associated with this inflammatory condition. Interstitial lung disease related to oncological drugs is a relevant problem in clinical practice. The etiopathogenetic mechanisms underlying this adverse event are not completely known but can be partly explained by the mechanism of action of the drug involved. Therefore, knowledge of the relevance of this potentially fatal adverse event supported by the reported safety data of pivotal studies becomes fundamental in the management of patients. The prompt diagnosis of drug-related pneumonia and the consequent differential diagnosis with other forms of pneumonia allow a rapid suspension of treatment and the establishment of an immunosuppressive treatment if necessary. In the context of the health emergency related to SARS CoV2 infection and COVID-19-related interstitial lung disease, such knowledge holds decisive relevance in the conscious choice of cancer treatments. Our intent was to describe the oncological drugs most correlated with this adverse event by reporting, where possible, the percentages of insurgency in pivotal studies to provide an overview and therefore promote greater awareness of this important toxicity related to oncological treatment.

Neutropenic Enterocolitis in the Treatment of Solid Tumors: A Case Report and Review of the Literature.

Neutropenic enterocolitis is a clinical condition characterized by inflammation of the colic mucosa, usually the caecum, associated with bowel wall thickening in patients with compromised immune system due to chemotherapy treatments. It can occur as well in other clinical conditions that lead to immunosuppression. Clinically, patients present with abdominal pain, fever, and neutropenia on blood tests. A number of major and minor criteria have been suggested for the clinical diagnosis of typhlitis. The most sensitive radiological investigation is represented by a computed tomography scan. There are no guidelines for treatment, but some factors may lead the clinician to medical treatments or prompt surgery as the best choice in that particular patient. The most implicated chemotherapeutic regimens are those based on taxanes. Here, we present a clinical case of a young patient with breast cancer and a review of the state of the art of knowledge regarding neutropenic enterocolitis in adult patients undergoing chemotherapy for the treatment of solid tumors.

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.

Hair Loss Prevention by a Scalp Cooling Device in Early Breast Cancer Patients: The Poliambulanza Preliminary Experience.

BACKGROUND: The most effective agents in the treatment of breast cancer have a common side effect, the hair loss. Some studies reported a reduction of hair loss with the use of the scalp cooling device. Indeed, it decreases the drug accumulation in the hair follicles. We report our preliminary experience with a scalp cooling device in reducing chemotherapy-induced alopecia and related distress in breast cancer patients undergoing adjuvant chemotherapy. METHODS: Hair loss grading and treatment tolerability were evaluated during chemotherapy every 21 days and 3 weeks after the last cycle of chemotherapy via Dean's scale by patients and operators and a comfort analogic scale by patients. We administered the Hospital Anxiety and Depression Scale questionnaire at the baseline and at the end of treatment to assess the distress related to chemotherapy- induced alopecia. RESULTS: Among the 46 patients identified, 27 accepted the device. The eligible chemotherapy regimens included docetaxel+cyclophosphamide (TC), doxorubicin+cyclophosphamide (AC) and paclitaxel (P) weekly+trastuzumab (T). 24 pts (89%) completed the treatment; 3 pts (11%) treated with AC prematurely interrupted use of the scalp-cooling device due to inefficacy. After the last cycle of chemotherapy, the number of patient who perceived a HL < grade 2 was 16 (59%). The hair retention reported by operators has been higher (78%). 81.5% of patients well tolerated the treatment. CONCLUSION: In our study, the scalp-cooling device reduced chemotherapy-induced alopecia in taxane- based chemotherapy. Furthermore, it suggests a discordance in hair loss perception between patients and operators.

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.

Significance of neutrophil-to-lymphocyte ratio in Western advanced EGFR-mutated non-small cell lung cancer receiving a targeted therapy.

PURPOSE: Lung cancer is one of the leading causes of cancer-related death worldwide and, although targeted therapy with tyrosine kinase inhibitors has dramatically improved the rates of response and survival in advanced EGFR-mutated adenocarcinoma, the overall outcome remains unsatisfactory. Therefore, new prognostic factors, preferably simple, inexpensive, and easy to reproduce on a large scale, are needed. We performed a retrospective analysis of our database including 63 western Caucasian patients with advanced EGFR-mutated lung adenocarcinoma and receiving gefitinib, erlotinib, or afatinib as first- or second-line therapy. Several studies demonstrated a strong link between elevated neutrophil-to-lymphocyte ratio (NLR) and poor prognosis both in early and advanced stages of non-small-cell lung cancer (NSCLC). METHODS: From January 2011 to December 2015, 63 consecutive elegible patients with advanced EGFR-mutated NSCLC were included in this analysis from 5 institutions. The NLR was derived from the absolute neutrophil and the absolute lymphocyte counts of a full blood count and the cutoff value was determined according to the mean NLR level. RESULTS: Despite the small sample analyzed, we found that NLR has a prognostic role for progression-free survival (PFS) and overall survival (OS), reaching a statistically significant difference with a better PFS and OS in the lower NLR group. CONCLUSIONS: Pretreatment NLR seems to represent a reliable, simple, and easy to reproduce laboratory tool to predict outcome and response to cancer therapies in this setting of Western Caucasian patients with EGFR-mutated NSCLC.

Off-target effects and clinical outcome in metastatic colorectal cancer patients receiving regorafenib: The TRIBUTE analysis.

Regorafenib is an orally administered multikinase inhibitor indicated for the treatment of heavily pretreated metastatic colorectal cancer patients with good performance status, albeit less than 50% treated patients achieve disease stabilisation or better at the first radiological evaluation. In addition to that a particularly broad spectrum of toxicities (experienced as G3 or more NCI CTCAE graded by 50% of patients treated) have led to reconsider its widespread use in the majority of patients. We retrospectively collected data about the magnitude of off-target effects experienced during the first 8-weeks of regorafenib monotherapy and analysed their correlation with overall survival, progression free survival and disease control rate. Our findings suggest that skin rash (Exp (B): 0.52, p = 0.0133) or hypothyroidism (Exp (B): 0.11, p = 0.0349) were significantly correlated with improved overall survival at multivariate regression analysis. It was also demonstrated a statistically significant role of diarrhea as predictor of improved survival but its independent prognostic role was lost at multivariate analysis (Exp (B): 0.63, p = 0.162). This is the first analysis showing a potential correlation between the onset of these forms of side effects and regorafenib efficacy, however sample size limitations and the retrospective nature of our analysis prevent us from drawing definitive conclusions.

GEMOX: An Active Regimen for the Treatment of Luminal and Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer.

BACKGROUND: Pretreated metastatic breast cancer (MBC) remains a formidable challenge with unmet needs both in terms of prolonged survival and quality-of-life-related issues. METHODS: We collected data from 27 MBC patients treated with gemcitabine and oxaliplatin (GEMOX) at our institution between June 2009 and April 2015. The patients were heavily pretreated, and all had previously been exposed to anthracyclines and taxanes. RESULTS: We achieved a complete response in 1 patient (4%), a partial response in 7 patients (26%) and stable disease in 12 patients (44%), while 6 patients (22%) experienced progressive disease. The response of 1 patient (4%) could not be evaluated because she interrupted her treatment during the first cycle due to a major reaction to oxaliplatin. We observed grade 4 hypertransaminasaemia in only 1 patient (4%) and grade 2 neuropathy in 16 patients (59%). Grade 3 leuconeutropenia was observed in 5 patients (18%). The median progression-free survival was 5.9 months and the median overall survival was 9.6 months. CONCLUSIONS: GEMOX is an efficient and well-tolerated salvage regimen for MBC patients.

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.

Chemotherapy rechallenge after regorafenib treatment in metastatic colorectal cancer: still hope after the last hope?

INTRODUCTION: The introduction of biological agents in cancer therapy is changing the progression of metastatic colorectal cancer. Currently, resistance to biological agents is an emerging problem; the progression of the disease is caused by the development of resistant clones. According to some authors, these clones can be re-sensitized to traditional and previously utilized chemotherapy agents. The results of the CORRECT study demonstrated the efficacy of regorafenib monotherapy in both KRAS wild type and mutant pretreated patients (pts). Two recent reports showed the potential of reintroduction of chemotherapy, even after treatment with regorafenib. PATIENTS AND METHODS: We performed a retrospective review of clinical data from patients treated with regorafenib at our institution between March 2012 and March 2013. We analysed patient characteristics, KRAS/NRAS status, response to treatment (evaluated by RECIST v1.1 criteria) and survival. RESULTS: Regorafenib was administered to 128 patients, and 11 (8.6%) received post-regorafenib therapy (to our knowledge). Seven (63.6%) patients were wild type for KRAS/NRAS. Post-regorafenib therapy represented for all the patients at least the fourth line: all the pts received both oxaliplatin- and irinotecan-based chemotherapy, all of them were treated with bevacizumab, and 7 patients also received cetuximab. Eight patients (72.7%) were treated with standard chemotherapy after regorafenib (irinotecan monotherapy, capecitabine plus oxaliplatin or irinotecan, dacarbazine or raltitrexed), while 3 patients received an experimental therapy (clinical trial). Nine of the 11 (81.8%) patients had PD and 2 patients had SD. The median progression-free survival was 1.6+ months (range 0.5-3.5), the median OS post-regorafenib was 2.1+ months (range 0.5-10.2) and the 6-month OS was 27.3%. CONCLUSION: Our retrospective analysis showed that after regorafenib therapy, re-introduction of chemotherapy is possible. Unfortunately, we reported a high percentage of disease progression beyond regorafenib, which is likely due to the high percentage of heavily pretreated patients (some received four or five types of therapy before regorafenib). We think that regorafenib could represent a chemotherapy resensitizing agent; however, additional studies are needed in patients who have received less pretreatment.

Angiogenesis genotyping and clinical outcome during regorafenib treatment in metastatic colorectal cancer patients.

Regorafenib monotherapy is a potential option for metastatic colorectal cancer patients. However, the lack of predictive factors and the severe toxicities related to treatment have made its use in clinical practice challenging. Polymorphisms of VEGF and its receptor (VEGFR) genes might regulate angiogenesis and thus potentially influence outcome during anti-angiogenesis treatment such as regorafenib. Aim of our study was to evaluate the role of VEGF and VEGFR genotyping in determining clinical outcome for colorectal cancer patients receiving regorafenib. We retrospectively collected clinical data and samples (tumour or blood) of 138 metastatic colorectal cancer patients treated with regorafenib. We analysed the correlation of different VEGF-A, VEGF-C and VEGFR-1,2,3 single nucleotide polymorphisms (SNPs) with patients' progression-free survival (PFS) and overall survival (OS). Results from angiogenesis genotyping showed that only VEGF-A rs2010963 maintained an independent correlation with PFS and OS. Among clinical factors only ECOG PS was independently correlated with OS, whereas no correlation with PFS was evident. Grouping together those results allowed further patients stratification into 3 prognostic groups: favourable, intermediate and unfavourable. VEGF-A rs2010963 genotyping may represent an important tool for a more accurate selection of optimal candidates for regorafenib therapy.

QT Prolongation and Anticancer Drugs: Is it a Cardiologist's Worry? The Oncologist's Point of View.

Currently, many novel therapies are available for physicians treating cancer; some of them are associated with adverse cardiac events. One of the most worrisome cardiac event is QT prolongation, which is a risk factor for developing the potentially fatal torsade de pointe. Many classes of drugs, both anticancer and concomitant agents, are involved in this issue. We report a review of old and new commonly used agents with torsadogenic potential.

Pancreatic Cancer: Promises and Failures of Target Therapies.

Currently, few efficient therapies are available to battle pancreatic cancer. Mechanisms underlying this cancer are not well known and researchers are trying to identify new therapeutic targets. Here, we present a review of new treatments and their results in recent years.

Prognostic clinical factors in pretreated colorectal cancer patients receiving regorafenib: implications for clinical management.

BACKGROUND: We assessed the impact on survival of angiogenesis and inflammation-related factors, particularly LDH serum levels, platelet, neutrophil and lymphocyte counts, and neutrophil-to-lymphocyte ratio (NLR), in metastatic colorectal cancer patients receiving regorafenib monotherapy. METHODS: LDH serum levels, neutrophil, lymphocyte and platelet counts were collected at the start of regorafenib monotherapy. Cut-off values were calculated by ROC curve analysis. Survival analyses were performed by Kaplan-Meier method, and multivariate analysis by Cox method. RESULTS: A total of 208 patients were eligible for analysis. Among factors who were related with worse overall survival and who maintained their role at the multivariate analysis, high platelet count (Exp(b):1.4963, 95% CI:1.0130-2.2103, p = 0.0439) and high neutrophil/lymphocyte ratio (Exp(b):1.6963, 95% CI:1.0757-2.6751, p = 0.0237) were those who more deeply were related to worse overall survival. High lymphocyte count (Exp(b):0.4527, 95% CI:0.2801-0.7316, p = 0.0013) was correlated with improved overall survival. CONCLUSIONS: High neutrophil, high platelet, low lymphocyte count and/or high NLR may represent negative prognostic factors in patients receiving regorafenib monotherapy. It is advisable that these factors are taken into account in the design of subsequent trials in colorectal cancer patients receiving this drug.

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.

Oxaliplatin-induced hypersensitivity reaction: underlying mechanisms and management.

Hypersensitivity reactions are rare but feared drugs adverse effect. These reactions are not uncommon with anticancer drugs, such as taxanes, monoclonal antibodies, and platinum compounds. Oxaliplatinum, a third-generation platinum compound, one of the mainstay drugs in the treatment of many gastrointestinal cancers, can give rise to hypersensitivity reactions, sometimes with fatal outcomes. In this paper, we reviewed the incidence and mechanisms underlying the occurrence of this event, highlighting the most recent advances concerning the pathogenesis of the reaction and also reporting possible risk factors identified and the most effective treatment in preventing the onset of this event.

Blind Snipers: Relevant Off Target Effects of Non-chemotherapeutic Agents in Oncology: Review of the Literature.

In recent years an increasing attention is focused on the potential effects of drugs on cancer incidence and/or cancer survival. Many medications of common use, developed for a variety of medical non-cancer situations, have been found to have potential anti- cancer effects. In this article, we performed an overview of the literature evidence for several commonly used non-cancer medications, such as aspirin, beta-blockers, metformin and other anti- diabetics, cardiac glycosides, anticoagulant heparin, statins, psychotropic drugs, vitamins, calcium and estrogens which have been shown to have anticancer effects, in observational and experimental studies. A huge amount of data supports the idea that a few of these commonly used medicines could decrease cancer death-rate, particularly aspirin, statins and metformin, crosswise different types of cancer. To date, no mature data are available from randomized and prospective trials; perhaps, the results of some studies underway will allow us to answer some questions on the possible use of these drugs in our clinical practice in primary and secondary prevention, or even in adjuvant setting.

Chemotherapeutic options for colorectal cancer patients with cardiovascular diseases.

The high incidence of cardiovascular disease and colorectal cancer in the world's population means that these two conditions may coexist in the same patient. In addition fluoropyrimidines, backbone for the treatment of colorectal cancer in both early stage and advanced disease, have a well-characterized cardio-toxicity, which limits their use in patients with heart disease and limits their reintroduction in those patients who have shown this toxicity. For the treatment of this, increasing proportion of patients is now possible to consider fluoropyrimidines-free chemotherapy regimens that are examined in this work, with the attempt to provide a possible treatment algorithm for various situations encountered in clinical practice.

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.

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.