Sotorasib plus Panitumumab in Refractory Colorectal Cancer with Mutated KRAS G12C.

BACKGROUND: KRAS G12C is a mutation that occurs in approximately 3 to 4% of patients with metastatic colorectal cancer. Monotherapy with KRAS G12C inhibitors has yielded only modest efficacy. Combining the KRAS G12C inhibitor sotorasib with panitumumab, an epidermal growth factor receptor (EGFR) inhibitor, may be an effective strategy. METHODS: In this phase 3, multicenter, open-label, randomized trial, we assigned patients with chemorefractory metastatic colorectal cancer with mutated KRAS G12C who had not received previous treatment with a KRAS G12C inhibitor to receive sotorasib at a dose of 960 mg once daily plus panitumumab (53 patients), sotorasib at a dose of 240 mg once daily plus panitumumab (53 patients), or the investigator's choice of trifluridine-tipiracil or regorafenib (standard care; 54 patients). The primary end point was progression-free survival as assessed by blinded independent central review according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Key secondary end points were overall survival and objective response. RESULTS: After a median follow-up of 7.8 months (range, 0.1 to 13.9), the median progression-free survival was 5.6 months (95% confidence interval [CI], 4.2 to 6.3) and 3.9 months (95% CI, 3.7 to 5.8) in the 960-mg sotorasib-panitumumab and 240-mg sotorasib-panitumumab groups, respectively, as compared with 2.2 months (95% CI, 1.9 to 3.9) in the standard-care group. The hazard ratio for disease progression or death in the 960-mg sotorasib-panitumumab group as compared with the standard-care group was 0.49 (95% CI, 0.30 to 0.80; P = 0.006), and the hazard ratio in the 240-mg sotorasib-panitumumab group was 0.58 (95% CI, 0.36 to 0.93; P = 0.03). Overall survival data are maturing. The objective response was 26.4% (95% CI, 15.3 to 40.3), 5.7% (95% CI, 1.2 to 15.7), and 0% (95% CI, 0.0 to 6.6) in the 960-mg sotorasib-panitumumab, 240-mg sotorasib-panitumumab, and standard-care groups, respectively. Treatment-related adverse events of grade 3 or higher occurred in 35.8%, 30.2%, and 43.1% of patients, respectively. Skin-related toxic effects and hypomagnesemia were the most common adverse events observed with sotorasib-panitumumab. CONCLUSIONS: In this phase 3 trial of a KRAS G12C inhibitor plus an EGFR inhibitor in patients with chemorefractory metastatic colorectal cancer, both doses of sotorasib in combination with panitumumab resulted in longer progression-free survival than standard treatment. Toxic effects were as expected for either agent alone and resulted in few discontinuations of treatment. (Funded by Amgen; CodeBreaK 300 ClinicalTrials.gov number, NCT05198934.).

Dignity and time perspective: A pilot explorative study in cancer patients.

OBJECTIVES: This study investigated the possible correlation between emotional distress linked to dignity and dysfunctional temporal orientations in the oncological context. METHODS: We conducted an exploratory study between December 2020 and February 2021, referring to a sample of 107 patients in active treatment for solid tumors belonging to the Oncology Department of the Fondazione Poliambulanza (Brescia, Italy). We administered two self-report questionnaires: the Patient Dignity Inventory (PDI-IT) (Italian version, Grassi L, Costantini A, Caruso R, et al. (2017) Dignity and psychosocial-related variables in advanced and nonadvanced cancer patients by using the patient dignity inventory-Italian version. Journal of Pain and Symptom Management 53(2), 279-287), as a measure of perceived level of dignity, and the Italian version of the Zimbardo Time Perspective Inventory scale (ZTPI) (Zimbardo PG and Boyd JN (2009) Il paradosso del tempo. La nuova psicologia del tempo che cambierà la tua vita. Milano: Mondadori), as a measure of the experiential dimensions of time, such as past, present, and future. RESULTS: From the PDI-IT emerged that our sample reported high levels of physical and psychological distress. Furthermore, we founded higher distress in patients under 55 years (p = 0.04) and lower distress in retired patients (p = 0.01). The ZTPI showed in our patients prevailing orientations to the past-positive (39.3%) and the future (37.4%). We noticed a gender difference: men were mainly oriented to the future while women to the past-positive. Moreover, married subjects reported a prevalent orientation to past-positive and the future. Finally, data analysis found moderate positive correlation between the "Negative Past" dimension of ZTPI and high levels of physical (r = 0.203, p = 0.03) and psychological distress (r = 236, p = 0.01). SIGNIFICANCE OF RESULTS: In our experience in oncology, dignity and time perspective play a central role as indicators of the quality of care. Our study shows the importance of a treatment path that integrates the constructs of Dignity and Time Perspective to favor a better psychological adaptation.

Cancer and Covid-19: A preliminary study on the trauma aspects of coronavirus in cancer patients.

OBJECTIVE: Because of Covid 19, it has become necessary to revise the treatment of cancer patients ("how" and "when"). That has had important psychological repercussions. The purpose of this study is the evaluation of the impact of Covid19 in terms of Post-Traumatic Stress Disorder and Depression and the potential association with coping strategies. METHODS: We conducted an exploratory study with 106 patients undergoing treatment, using following questionnaires: Screening Questionnaire for Disaster Mental Health and Mini-Mental Adjustment to Cancer. RESULTS: Only 25.5% of our sample showed symptoms of posttraumatic stress disorder (PTSD) and 6.6% revealed a probable presence of depression. In addition, it came up a significant correlation between SQD_P and the coping styles "Hopelessness" (r = 0.41 p < 0.001) and "Anxious Preoccupation" (r = 0.45, p < 0.001). A strong correlation also emerged between non-Covid 19 patients and PTSD (r = 0.29, p = 0.002). CONCLUSIONS: Our preliminary data did not reveal a prevalence of PTSD, but the persistence of the health emergency requires to focus future research on protective and risk factors related to PTSD and psychological distress in cancer patients, in order to reduce the mental health burden of Covid19.

Antibiotics and steroids, the double enemies of anticancer immunotherapy: a review of the literature.

The advent of immunotherapy in onco-haematology has represented a kind of revolution that has been able to modify the prognosis of numerous tumours that until recently would have been rapidly lethal. While much is known about the mechanism of action of these drugs, relatively little is known about the factors that represent potential predictors of response and toxicity. Among these factors, the simultaneous administration of antibiotics and/or steroids seems to have a negative impact. Furthermore, several retrospective studies have highlighted the strong link between cancer and gut microbiota, regardless of the tumour site, and how microbiota, playing a key role in the prevention of systemic inflammation at various levels and in the intestinal homeostasis, can be negatively influenced by the dysbiosis caused by antibiotic therapy administered during or in the weeks immediately preceding the start of immunotherapy. Moreover, we assume that the concurrent administration of steroids, which is often necessary in cancer patients, likely results in a deleterious effect on the therapeutic outcomes of immunotherapy. In this review, we will try to clarify the evidence on the possible detrimental effects of antibiotics and steroids, which are currently considered the double enemies of anticancer immunotherapy.

The role of primary tumour sidedness, EGFR gene copy number and EGFR promoter methylation in RAS/BRAF wild-type colorectal cancer patients receiving irinotecan/cetuximab.

BACKGROUND: The data from randomised trials suggested that primary tumour sidedness could represent a prognostic and predictive factor in colorectal cancer (CRC) patients, particularly during treatment with anti-epidermal growth factor receptor (EGFR) therapy. However, an in-deep molecular selection might overcome the predictive role of primary tumour location in this setting. METHODS: We conducted a retrospective analysis in which tumour samples from RAS/BRAF wild-type (WT) metastatic CRC patients treated with second-third-line irinotecan/cetuximab were analysed for EGFR gene copy number (GCN) and promoter methylation. Study objective was to evaluate the correlation of tumour sidedness, EGFR promoter methylation and EGFR GCN with clinical outcome. Median follow-up duration was 14.3 months. RESULTS: Eighty-eight patients were included in the study, 27.3% had right-sided CRC, 72.7% had left-sided CRC; 36.4% had EGFR GCN<2.12 tumour, 63.6% had EGFR GCN⩾2.12 tumour; 50% had EGFR promoter-methylated tumour. Right-sided colorectal cancer (RSCRC) were associated with reduced overall response rate (ORR) (4.2% for RSCRC vs 35.9% for left sided colorectal cancer (LSCRC), P=0.0030), shorter progression-free survival (PFS) (3.0 vs 6.75 months, P<0.0001) and shorter overall survival (OS) (8 vs 13.6 months, P<0.0001). EGFR GCN<2.12 tumours were associated with reduced ORR (6.2% for EGFR GCN<2.12 vs 39.3% for EGFR GCN⩾2.12 tumours, P=0.0009), shorter PFS (3.5 vs 6.5 months, P=0.0006) and shorter OS (8.5 vs 14.0 months, P<0.0001). Epidermal growth factor receptor-methylated tumours were associated with reduced ORR (9.1% for methylated vs 45.5% for unmethylated, P=0.0001), shorter PFS (3 vs 7.67 months, P<0.0001) and shorter OS (8 vs 17 months, P<0.0001). At multivariate analysis, EGFR GCN and EGFR promoter methylation maintained their independent role for ORR (respectively P=0.0082 and 0.0025), PFS (respectively P=0.0048 and<0.0001) and OS (respectively P=0.0001 and<0.0001). CONCLUSIONS: In our study, an accurate molecular selection based on an all RAS and BRAF analysis along with EGFR GCN and EGFR promoter methylation status seems to be more relevant than primary tumour sidedness in the prediction of clinical outcome during cetuximab/irinotecan therapy. However, these data need to be validated with future prospective and translational studies.

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.

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.

Second-Line Treatment Options for Small-Cell Lung Cancer: A Light at the End of the Tunnel.

Small-cell lung cancer (SCLC) is a subtype of lung tumor characterized by rapid growth and early metastatic dissemination. It represents approximately 15% of all diagnosed lung cancers, with an annual incidence of over 200,000 cases worldwide. At the time of initial diagnosis, approximately 75-80% of patients already have extrathoracic spread. Almost all patients with SCLC also relapse after achieving a complete response with first-line treatment. Outcomes achievable in second-line treatment are related to the length of time between completion of first-line therapy and disease progression. While first-line chemo-immunotherapy remains the standard of care for initial management, the role of second-line treatment strategies in SCLC has been a topic of significant research and discussion. Second-line treatment options are limited and the results are still disappointing. Several molecules are currently being studied in lines following the first, using immunological targets and cell cycle checkpoints. Among these, particular interest has been placed on anti-PD-1 (programmed cell death-1 protein) and anti-PD-L1 (programmed cell death-ligand 1) monoclonal antibodies, and DLL3 (Delta-like ligand 3), which are being evaluated alone or in combination. Tarlatamab is a novel promising therapeutic antibody currently under investigation for its potential use in previously treated SCLC patients. This mini-review will explore the current state of second-line treatment options for SCLC, their clinical efficacy, and future directions.

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.

Low-Dose Immunotherapy: Is It Just an Illusion?

The development and use of immunotherapy in the last decade have led to a drastic improvement in results in the onco-haematological field. This has implied, on the one hand, the need for clinicians to manage a new type of adverse event and, on the other hand, a significant increase in costs. However, emerging scientific evidence suggests that, as with other drugs in the recent past, the registry dosage can be drastically reduced for immunotherapies without penalizing their effectiveness. This would also lead to an important reduction in costs, expanding the audience of cancer patients who could access immunotherapy-based treatments. In this "Commentary", we analyze the available evidence of pharmacokinetics and pharmacodynamics and the most recent literature in favor of low-dose immunotherapy.

Cancer Patients' Attitudes Towards the Anti-Covid-19 Vaccine: A Collective Case Study.

AIM: The purpose of the present study was to determine cancer patients' attitudes toward the anti-COVID-19 vaccine. BACKGROUND: Historically, the scientific community's responsibility was to investigate attitudes about vaccination. The course of COVID-19 in cancer patients makes them a high priority for vaccination. Cancer patients are at greater risk of serious complications and death because of COVID-19 infection. OBJECTIVE: The purpose of the present study was to determine cancer patients' attitudes toward the anti-COVID-19 vaccine. We examined several constructs that potentially influenced cancer patients' perceptions of the vaccine: health status, knowledge of COVID-19 and vaccination, cancer patients' perceptions of vulnerability, and attitudes toward general vaccines. METHODS: We conducted a collective case study with 200 cancer patients undergoing treatment, and divided the sample into two groups: patients who "expected to heal" (Group A) and patients who "expected to chronicize" (Group B). Data were collected through a purpose-built questionnaire consisting of 22 questions and a study of medical records. RESULTS: Data analysis showed that both groups, Group A (M= 3.89 SD= 0.64) and Group B (M= 3.98 SD= 0.64), had a favorable attitude toward the anti-COVID-19 vaccine. This favorable attitude toward the anti-COVID-19 vaccine depended on several factors: perception of vulnerability to COVID-19, perception of the severity of their oncological situation, and communication with oncologists. CONCLUSION: Our study highlighted the plurality of factors that influence attitudes toward the anti-COVID-19 vaccine. It is theref+ore of fundamental importance to increase the use of the shared decision-making approach (SDM) to guide the patient to an informed choice.

Controversial link between proton pump inhibitors and anticancer agents: review of the literature.

Drug-drug interactions represent a topic of great interest, not only due to the risk of unexpected adverse events but also due to the possibility of altering the effectiveness of a specific treatment. Inappropriate or concomitant use of drugs can often lead to changes in the bioavailability of various compounds, resulting in pharmacokinetic alterations. A recent example is the concomitant administration of proton pump inhibitors (PPIs) and anticancer agents. PPIs are overused beyond their classic indications, resulting in a high risk of interactions with other drugs, such as anticancer agents, both PO and intravenous. However, the real clinical impact of concomitant acid suppression therapy and anticancer therapies remains controversial and is not yet fully understood. Certainly, the gut microbiota plays a key role in regulating the response of the immune system, and PPIs can significantly alter the gut microbiome, resulting in gut dysbiosis. Indeed, while the link sometimes appears to lead to negative outcomes, as in the case of immunotherapy, oral capecitabine, or tyrosine kinase inhibitors, in other cases, it seems to enhance the effectiveness of intravenous chemotherapy. In this review, I analyse the possible drug interactions between PPIs and the main classes of anticancer drugs.

Chemotherapy use at the end of life. A retrospective single centre experience analysis.

AIMS AND BACKGROUND: The aim of the study was to evaluate the attitude at our institution in using chemotherapy at the end of life in oncology patients. We compared our habits with other clinical patterns in medical oncology, calculating the temporal interval between the last chemotherapy administration and death of the patient. PATIENTS AND METHODS: We selected and analyzed 102 patients who received chemotherapy for metastatic or advanced solid tumors (breast, colon, gastric, pancreatic and lung cancers) and who died either in or out of a hospital or hospice from June 2007 to the end of 2009. RESULTS: We compared 51 patients enrolled in clinical trials with 51 patients not enrolled in clinical trials. Patients of both groups died with advanced cancer between June 2007 and 2009. The following solid tumor types were represented: 48% colorectal cancer, 22% breast cancer, 30% other solid tumors (pancreatic, lung and gastric cancer). The median age at death was 62 years (range, 39 to 84), the male/female ratio was 52:50, and 69% of the patients were married. Most patients, 54%, received 2-3 lines of chemotherapy, 25% received more than 3 lines, and the remaining 21% one line only of chemotherapy. Of the 102 patients identified, 16 (16%) received chemotherapy in the last month of life, and 6 (6%) of these in the last 2 weeks. We speculated that the presence of palliative care services in the territory of residence of patients could influence the time interval between the last chemotherapy and death. We found that 52 patients (51%) lived in areas where palliative care services were not available, 27 (52%) of them received chemotherapy in the last 3 months, 8 (15%) in the last month, and 5 (10%) within the last 2 weeks of life. In contrast, of the 49 patients living in the territory served by palliative care units or a hospice, none received chemotherapy during the last 2 weeks of life and 37% received it during the last 3 months of life (P = 0.003). CONCLUSIONS: Among selected patients who died for advanced cancer in our Operative Unit from 2007 to 2009, 50% received chemotherapy in the last 3 months of life. The availability of palliative care services in the territory of residence of patients can influence the interval between the last chemotherapy administration and death.

Clinical Characterisation and Management of the Main Treatment-Induced Toxicities in Patients with Hepatocellular Carcinoma and Cirrhosis.

The incidence of hepatocellular carcinoma (HCC) continues to increase worldwide, particularly in Western countries. In almost all cases, HCC develops in subjects with hepatic cirrhosis, often as the result of hepatitis B or C virus infection, alcohol abuse or metabolic forms secondary to non-alcoholic steatohepatitis. Patients with HCC and hepatic symptoms can therefore present symptoms that are attributable to both conditions. These patients require multidisciplinary management, calling for close interaction between the hepatologist and the oncologist. Indeed, the treatment of HCC requires, depending on the disease stage and the degree of hepatic impairment, locoregional therapies that can in turn be broken down into surgical and nonsurgical treatments and systemic treatments used in the event of progression after the administration of locoregional treatments. The past decade has seen the publication of countless papers of great interest that have radically changed the scenario of treatment for HCC. Novel therapies with biological agents and immunotherapy have come to be standard options in the approach to treatment of this cancer, obtaining very promising results where in the past chemotherapy was almost never able to have an impact on the course of the disease. However, in addition to being costly, these drugs are not devoid of adverse effects and their management cannot forgo the consideration of the underlying hepatic impairment. Patients with HCC and cirrhosis therefore require special attention, starting from the initial characterisation needed for an appropriate selection of those to be referred for treatment, as these patients are almost never fit. In this chapter, we will attempt to investigate and clarify the key points of the management of the main toxicities induced by locoregional and systemic treatments for HCC secondary to cirrhosis.

Quality of life in colon cancer patients with skin side effects: preliminary results from a monocentric cross sectional study.

BACKGROUND: Epidermal growth factor receptor inhibitors are widely prescribed anticancer drugs. Patients treated commonly develop dermatologic adverse drugs reactions, but rarely they are involved in systematic evaluation of their quality of life. This monocentric cross sectional study is carried out to assess quality of life in colon cancer patients experienced skin side effects due to anti epidermal growth factor receptor inhibitors therapy. METHODS: Consecutive patients with skin side effects to therapy treated at Fondazione Poliambulanza were enrolled in this study. Quality of life was evaluated with the Italian validated version of Skindex-29 questionnaire, exploring three dimensions: symptoms, emotional, and physical functioning. Skindex-29 was administered one time between the eighth and the twelfth week of the treatment. RESULTS: Forty-five consecutive patients, mainly with metastatic colon cancer (29 female, 16 male), with an average age of 59.31 years (ranging from 34-78) were included in the study and analyzed. Patients showed a great impact of skin side effects on symptoms (mean 43), followed by emotional (mean 30), and functioning (mean 26) scales. In general women, the 55-65 age class, and patients with partial remission reported the worst quality of life. CONCLUSIONS: Epidermal growth factor receptor inhibitors' skin side effects have an important impact on quality of life in advanced colon cancer patients; symptoms scale is the most effect respect to emotional and functioning scales.

Innovative Approach for the Prevention of Chemotherapy-Induced Peripheral Neuropathy in Cancer Patients: A Pilot Study With the Hilotherm Device, the Poliambulanza Hospital Experience.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is an adverse event of taxanes, with no effective prevention or treatment available and a highly negative impact on patient quality of life. The aim of this study is to asses that the constant application of cooled cuffs on the hands and feet prevent and mitigate CIPN. METHODS: Patients with breast, gynecologic, and pancreatic cancer who received weekly paclitaxel (PTX), PTX/carboplatin, and nab-paclitaxel (nab-PTX)/gemcitabine for any indication at the therapeutic scheduled dosage were included in this prospective study. Hilotherm Chemo care device forms a closed-loop system with cuffs and tubes through which a coolant flows at a temperature of 10 °C. CIPN was monitored using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (edition 3.0), and the tolerability and side effects were scored by using the Common Terminology Criteria for Adverse Events (T4.03 2017). RESULTS: To date, we have enrolled 64 patients. Of these, 54 (84%) completed all cooling cycles. Continuous cooling was well tolerated by all patients. No patients had grade >2 CIPN or had serious or lasting adverse events as a result of Hilotherapy. The median time to CIPN onset was 77 days for the entire population. CONCLUSION: Hilotherapy has good effectiveness and tolerability and seems to be able to prevent or reduce the symptoms of CIPN. We are still recruiting patients to obtain more data and to collect data at 3 months after the end of chemotherapy. Prospective studies seem to be warranted.

Malignant Pleural Effusion: Still a Long Way to Go.

BACKGROUND: Malignant pleural effusion, which is a common clinical problem in patients with cancer, may be due to both primary thoracic tumours or to a metastatic spread in the chest and constitutes the first sign of disease in approximately 10% of patients. Almost all cancers can potentially produce a pleural effusion. The presence of malignant tumour cells in the pleural fluid is generally indicative of advanced disease and is associated with high morbidity and mortality with reduced therapeutic options. Dyspnoea during mild physical activity or at rest is generally the typical sign of restrictive respiratory failure. METHODS: This is a systematic review of all the main articles in the English language on the topic of malignant pleural effusion and reported by the Pubmed database from 1959 to 2018. I reviewed the literature and guidelines with the aims to focus on what is known and on future pathways to follow the diagnosis and treatment of malignant pleural effusions. RESULTS: The main goal of palliation of a malignant pleural effusion is a quick improvement in dyspnoea, while thoracentesis under ultrasound guidance is the treatment of choice for patients with a limited life expectancy or who are not candidates for more invasive procedures such as drainage using an indwelling small pleural catheter, chemical pleurodesis with sclerosing agents, pleurectomy or pleuro-peritoneal shunt. CONCLUSION: Despite progress in therapeutic options, the prognosis remains severe, and the average survival is 4-9 months from the diagnosis of malignant pleural effusion. Moreover, mortality is higher for patients with malignant pleural effusion compared with those with metastatic cancer but no malignant pleural effusion. Therefore, the prognosis of these patients primarily depends on the underlying disease and the extension of a primary tumour. This review focuses on the most relevant updates in the management of malignant pleural effusion.

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.

Dyspnea in Cancer Patients: A Well-Known and Neglected Symptom.

BACKGROUND: Dyspnea is a very common and well-known symptom in patients with advanced cancer, but it is often neglected by physicians. Moreover, despite the high frequency of dyspnea, few controlled studies have been conducted on cancer patients. In most cases, this 'awareness of breathing with difficulty' and its severity can only be judged by the patient. Moderate or severe dyspnea is described in 20-80% of patients with advanced cancer and breathlessness is considered a prognostic factor for shorter survival, either alone or associated with other parameters. METHODS: I reviewed the literature and guidelines on the topic with the aims to focus on what is known and on future pathways to follow for the diagnosis and treatment of dyspnea. RESULTS: There is no uniformity regarding the definition of dyspnea; consequently, there is still no general agreement about which tools are the best to use in clinical practice to detect the presence and severity of this symptom. In addition to the difficulty of assessing the symptom, a further limit concerns the management of dyspnea: a very limited number of therapies, both pharmacological and otherwise, are currently available that lead to satisfactory outcomes. Opioids such as morphine remain the cornerstone of treating dyspnea. CONCLUSION: Dyspnea is a complex, multidimensional symptom that results from an interaction between factors and their causes, perception and expression. The main target of assessment and management is the intensity of dyspnea, as expressed by the patient, rather than the objective parameters of the disease. Although dyspnea is a very common symptom, debilitating and often difficult to control, especially in the terminal phase of the disease, few controlled studies have been conducted on cancer patients. Dyspnea remains a well-known but neglected symptom in advanced and terminal cancer patients. Future studies should be conducted regarding the careful assessment and management of this symptom.