Raffaele Giusti

Clinical impact of sequential treatment with ALK-TKIs in patients with advanced ALK-positive non-small cell lung cancer: Results of a multicenter analysis

OBJECTIVES Anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) is sensitive to treatment with an ALK-tyrosine kinase inhibitor (-TKI). However, the benefit of sequential treatment with a 2nd ALK-TKI in patients who fail a 1st ALK-TKI has been poorly addressed. MATERIALS AND METHODS We collected the data of 69 advanced ALK-positive NSCLCs who were treated with one or more ALK-TKIs at three Italian institutions. The clinical outcome of treatment with an ALK-TKI and the patterns of treatment upon failing a 1st ALK-TKI were recorded. RESULTS Objective response rate (ORR) and median progression-free survival (PFS) on a 1st ALK-TKI (mostly crizotinib) were 60.9% and 12 months, respectively. Of the 50 patients who progressed on a 1st ALK-TKI, 22 were further treated with a 2nd ALK-TKI (either ceritinib or alectinib), for whom an ORR of 86.4% and median PFS of 7 months, respectively, were reported. Conversely, 13 patients underwent rapid clinical/radiographic disease progression leading to death shortly after discontinuation of the 1st ALK-TKI, 7 patients were managed with a 1st ALK-TKI beyond progression, and 8 patients transitioned to other systemic treatments (mostly chemotherapy). Post-progression survival (PPS) significantly favored the 22 patients who were sequentially treated with a 2nd ALK-TKI over those who transitioned to other systemic treatments (P=0.03), but not versus those who were treated with a 1st ALK-TKI beyond progression (P=0.89). CONCLUSION Sequential treatment with a 2nd ALK-TKI is effective in patients who fail a 1st ALK-TKI. Continuous ALK-inhibition upon failing a 1st ALK-TKI may be associated with improved clinical outcome.

Integration between oncology and palliative care: does one size fit all?

ABSTRACT This is a letter to the editor with critical appraisal of some aspects about indicators of integration of oncology and palliative care programs analyzed by David Hui et al. in a recent paper published on Annals Of Oncology -Ann Oncol 2015; 26(9): 1953-1959.

Pulmonary Fibrosis after Pegylated Liposomal Doxorubicin in Elderly Patient with Cutaneous Angiosarcoma

Introduction. Angiosarcoma is a rare cancer of the inner lining of blood vessels and can arise anywhere in the body, most commonly presenting as cutaneous disease in elderly patient, involving head and neck (H&N), especially the scalp. Pegylated liposomal doxorubicin (PLD) is one of the available treatments in patients with advanced or metastatic disease. Common toxicities are myelosuppression, palmar-plantar erythrodysesthesia, nausea, and stomatitis. Regarding PLD-related pulmonary fibrosis in an uncommon toxicity, there are few cases reported in literature. None of these occurred in angiosarcoma. Methods. This is a case report describing an elderly patient treated with PLD for advanced H&N cutaneous angiosarcoma who developed G5 pulmonary toxicity after the second PLD administration. Results. According to our data and patient clinical outcome, we believe that she passed away from fatal PLD-induced pulmonary fibrosis. This is the first case of fatal interstitial pneumonitis in a 77-year-old woman treated with PLD for angiosarcoma. The case has been reported for its rarity. Conclusions. Pathophysiology of this phenomenon is still unclear and more studies are necessary to understand the true incidence of pulmonary toxicities in patients in treatments with PLD and its mechanism.

Knowledge and Attitudes of Young Italian Medical Oncologists Toward the Approach and Treatment of Pain: No Changes, Despite the Law

In 2001, Visentin et al. published the results from a single-center survey on basic knowledge and attitudes of physicians and nurses toward pain, conducted in an Italian hospital. Based on the percentage of correct answers (from 30% to 96%), they concluded that there were significant knowledge deficits and erroneous beliefs that might hamper treatment of the patient in pain and that these results would help in designing educational programs aimed at improving pain treatment [1]. In 2002, during the 4th Italian National Congress of Medical Oncology, we administered the same questionnaire to 100 residents in oncology. The median overall percentage of correct answers was 89%, which varied from 35% to 97% among the different items: 75.4% for items regarding the use of analgesics, 87.2% for items regarding attention to pain, and 73.3% for items regarding pain in children. In our opinion, these results indicated that the knowledge and attitudes about treatment of pain among residents in oncology might be considered adequate [2]. Educational programs on core competencies in the assessment and management of cancer pain have likely driven an improvement in the last years. Moreover, the Italian legislation now also protects patients’ rights by setting “measures to guarantee the access to palliative and pain treatments” (Law 38/ 2010) [3]. Nevertheless, we still observed barriers and limitations in pain-related knowledge and practice among the oncology community.

Comment on ‘What to Do, and What Not to Do, When Diagnosing and Treating Breakthrough Cancer Pain: Expert Opinion’

Breakthrough pain (BTP) is a transient exacerbation of pain that occurs either spontaneously or in relation to a specific predictable or unpredictable trigger despite an adequately controlled background pain. Breakthrough pain is usually related to the background pain and is of rapid onset, severe in intensity and generally self-limiting, with a mean duration of 30 min [1]. BTP is usually managed by the administration of supplemental oral analgesic drugs at a proportional dose to the total around-the-clock opioid amount [2]. We read the paper published inDrugs byVellucci et al. [3] and we believe that it represents a good and well-structured clinical recommendation on the best available evidence for breakthrough cancer pain (BTcP) management. But our question is, why another paper on BTcP management? Can another published paper help to clarify some of the most essential aspects of BTcP like terminology, definition, epidemiology, assessment as well as diagnosis and treatment? To answer to our question, in March 2016 we performed a literature search on MEDLINE with the following search terms: ‘‘breakthrough cancer pain’’ OR ‘‘BTcP’’ AND Consensus OR Delphi OR recommendation* OR ‘‘expert opinion’’. We identified 14 articles (13 ? 1 noneligible paper) consisting of consensus, Delphi studies or recommendations about BTcP. Six of these papers (46 %) have been published in the last 2 years (2015–2016) and four (31 %) in 2016 (Table 1). We do not think more is necessarily better in this instance. Thomas H. Lee states in his editorial published on March 2016 on the Journal of American Medical Association [4] that guidelines and performance measures are helpful when clear evidence on a subject exists. Moreover, guidelines turn out to be even more valuable for subjects who don’t have right or wrong answers. In these cases guidelines, consensus and recommendations, edited by experienced and knowledgeable colleagues, can help clinicians to approach the decision-making process. Guidelines can define protocols for the management of situations for which clear evidence is not available. Nonetheless, onAugust 2015, theCochraneEditorial Unit (CEU) advised that the Cochrane systematic review on the use of opioids for themanagement ofBTcP in cancer patients [5] should be withdrawn. In fact, according to the feedback provided by different authors on the Cochrane Library web page, the systematic review has turned out to be misleading. ‘‘It is very unusual to find a Cochrane Review of poor quality and we have never seen it before’’, said Ruiz-Garcia et al. on their rapid response to the British Medical Journal [6] about Cochrane’s transparency and the use fentanyl for the management of breakthrough pain in cancer patients. So, how can the physician evaluate which drug is the most appropriate for each patient? The decision-making process involves a range of different factors. Only one of these factors regards the costs of the new drugs, which may even be 600 times more expensive than the older ones. & Raffaele Giusti raffaelegiusti@yahoo.it; rgiusti@ospedalesantandrea.it

The use of fentanyl in pain management in head and neck cancer patients: a narrative review

Background: Head and neck (H&N) cancers account for about 5% of all malignant tumours. Pain is one of the most feared consequences of H&N neoplasms and is experienced by up to 80% of patients and worsens their quality of life inhibiting speaking, eating, drinking or swallowing. Nevertheless, pain is still often underestimated and undertreated. Objectives: The role of opioids in cancer pain has been well established but evidences about the role and the relative effectiveness of opioids such as fentanyl in the context of H&N cancer pain remains unclear. Methods: A literature review based on the guidance of the Centre for Reviews and Dissemination was conducted. An iterative approach was used starting with an electronic search in the MEDLINE database. The search terms ((‘Neoplasms’[Mesh]) AND ‘Head and Neck Neoplasms’[Mesh]) AND ‘Fentanyl’[Mesh] were used. Results: A total of 18 publications were found by the first performed search on PubMed. Other publications concordant with our aim were found by cross-reference. Considering inclusion and exclusion criteria for our review, eight papers resulted eligible for analysis. Conclusion: Fentanyl transdermal therapeutic system (TTS) seems to be an important option, thanks to the way of administration, the good safety and tolerability profiles to control baseline pain. For breakthrough cancer pain (BTcP), several formulations of transmucosal fentanyl are available. All the formulations seem to be active and safety but we lack head-to-head studies of fentanyl versus other strong opioids, as well as with different formulation of fentanyl, particularly for BTcP where H&N cancer population is very poorly represented.

Caring for Cancer Patients After the Italian Earthquakes: A Proposal From the Field

The recent earthquake that shook Central Italy confirmed once again the country’s vulnerability. These events have serious consequences on the lives of cancer patients and on the organization of health care assistance. After the earthquake in Central Italy, as well as after the ones in L’Aquila and Emilia Romagna, nearby hospitals were declared unfit. Thus, patients were deprived of their reference health center. In addition, patients were condemned to live in emergency tents or to move to other cities, and health care management at home was even more complex.

Is it possible to teach pain therapy playing basketball

If in your 60 s somebody tells you: “You are good only at two things: coaching a basketball team and oncology”, I guess you would question everything you have done so far. Yet, in my case, it is probably true.

Multidisciplinary approach to fetal adenocarcinoma of the lung: A case report

This paper reports a case of high‐grade fetal lung adenocarcinoma with particularly aggressive clinical and biological features in a 57‐year‐old man. Our patient first underwent neoadjuvant chemotherapy followed by surgery, and was then treated with adjuvant chemotherapy. Next, he had radiotherapy on the mediastinal region and prophylactic whole brain radiation therapy (WBRT). Following radiotherapy treatment, the patient started maintenance therapy with a somatostatin analogue. After 58 months of follow‐up he is asymptomatic and disease free.