Efficacy of nilotinib as third-line treatment in a patient with very late Chronic Myeloid Leukemia and a possibile cardiologic contraindication

We report a case of a patient with chronic myeloid leukemia who was treated with nilotinib after failure to imatinib and dasatinib. The patient, diagnosed in 1998, was cytogenetically resistant to imatinib. She was switched to dasatinib and achieved a major cytogenetic response, but 3 years later a mutant clone emerged responsible for cytogenetic relapse. The mutation we detected was V299L, that is resistant in vitro to dasatinib, while maintaining a good sensitivity to nilotinib. As the patient was not eligible for allotransplat, we decided to switch to nilotinib, despite a ECG abnormality (wandering pace-maker). After one-year treatment, the patient is in complete cytogenetic response with a low BCR-ABL/ABL transcript ratio. On mutational analysis, the V299L mutation has disappeared. Any cardiologic toxicity has not been observed so far. This case proves that ECG abnormalities do not represent an absolute contraindication to nilotinib and that nilotinib can be effective as third-line BCR-ABL inhibitor

Monitoring for cytomegalovirus and Epstein-Barr virus infection in chronic lymphocytic leukemia patients receiving i.v. fludarabine-cyclophosphamide combination and alemtuzumab as consolidation therapy.

The combination of fludarabine and cyclophosphamide (FC) has become the standard of care in chronic lymphocytic leukemia (CLL) patients. Due to the well-recognized F-related immunosuppression,[1][1] a higher risk of opportunistic infections could be expected by adding another immunosuppressive agen

Eliciting Preferences for Clinical Follow-Up in Patients with Head and Neck Cancer Using Best-Worst Scaling.

OBJECTIVES: There are no commonly accepted standards for monitoring patients treated for head and neck cancer. The aim of this study was to assess patients' preferences for different aspects of follow-up. METHODS: A best-worst survey was conducted in a sample of head and neck cancer patients in clinical follow-up at the National Cancer Institute (Milan, Italy). Conditional logit regression with choice as the dependent variable was run to analyse the data. A covariate-adjusted analysis was performed in order to identify socio-demographic and clinical factors related to the selection of best-worst items. The participants were asked to report any difficulties encountered during the survey. RESULTS: A total of 143 patients, predominantly male (74%) and with a mean age of 58 years were enrolled in the survey. The strongest positive preference was expressed for a hospital-based program of physical examinations with frequency decreasing over time. Conversely, the lowest valued item was not performing any positron emission tomography (PET) scan during follow-up. Patients with high educational levels were more likely to value attending a primary care-based program and undergoing intensive radiological investigations. Other patient-specific variables significantly associated with the choice of items were employment and living status, time already spent in follow-up and number of treatments received. CONCLUSIONS: Overall, patients were more likely to choose an intensive follow-up scheme broadly consistent with the program currently administered by the hospital. There is little evidence of preference heterogeneity that might justify customized programs based on demographics. The best-worst scaling task appeared feasible for most participants

Long-term Events in Adult Patients with Clinical Stage IA-IIA Nonbulky Hodgkin's Lymphoma Treated with Four Cycles of Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine and Adjuvant Radiotherapy: A Single-Institution 15-Year Follow-up

Abstract Purpose: To report on long-term events after short doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy and adjuvant radiotherapy in favorable early-stage Hodgkin's lymphoma. Experimental Design: We monitored late events and causes of death over 15 years (median follow-up, 120 months) in 120 patients with nonbulky stage IA-IIA Hodgkin's lymphoma, treated with four cycles of ABVD and limited radiotherapy. Pulmonary and cardiac function tests were done throughout the follow-up. Outcome measures included cause-specific mortality, standardized mortality ratio, and standardized incidence ratio for secondary neoplasia. Results: Projected 15-year event-free and overall survival were 78% and 86%, and tumor mortality was 3%. Standardized mortality ratio was significantly higher than 1 for both males (2.8; P = 0.029) and females (9.4; P = 0.003). The risk of cardiovascular events at 5 and 12 years was 5.5% and 14%, with a median latent time of 67 months (range: 23-179 months) from the end of radiotherapy. Pulmonary toxicity developed in 8% of patients; all had received mediastinal irradiation and the median time from radiotherapy to pulmonary sequelae was 76 weeks (range: 50-123 weeks). The risk of secondary neoplasia at 5 and 12 years was 4% and 8%, respectively, with no cases of leukemia. Fertility was preserved. Conclusions: Long-term events were mostly related to radiotherapy; the role of short ABVD chemotherapy was very limited, as documented by fertility preservation and lack of secondary myelodysplasia/leukemia. A proportion of patients died from causes unrelated to disease progression and the excess mortality risk was mostly due to the occurrence of secondary neoplasms and cardiovascular diseases. A moderate dose reduction of radiotherapy from 40-44 Gy to 30-36 Gy did not decrease the risk of late complications; abolishing radiotherapy in nonbulky early-stage Hodgkin's lymphoma is being evaluated

A year of pandemic for European particle radiotherapy:A survey on behalf of EPTN working group

OBJECTIVES: To provide an overview of the impact of the pandemic on the clinical activity and take a snapshot of the contingent challenges that European particle therapy centers are called to face, we surveyed the members of the European Particle Therapy Network (EPTN). MATERIAL AND METHODS: A 52-question survey was conducted from 4th April 2021 to 30th July 2021 using the Google Forms platform. Three dedicated sections analysed the clinical context of each participating institution, the staff management, and the clinical changes in the oncological workflow. RESULTS: Out of the 23 contacted European hubs of particle radiotherapy, a total of 9 (39%) responded to the survey. The number of in-person first evaluations and follow-up visits decreased, but telemedicine was implemented. Multidisciplinary tumour board discussions continued during the outbreak using web-based solutions. A delay in cancer diagnosis and oncological staging leading to an increment in more advanced diseases at first presentation was generally observed. Even if the total number of treatments (photons and particles) in the responding institutions showed a trend of decrease, there was or a stable situation or slight increase in particle treatments. The clinical treatment choices followed the national and international scientific recommendations and were patient/disease-oriented. Hypofractionation and short-schedule of chemotherapy, when applicable, were preferred. CONCLUSIONS: Our findings show a rapid and effective reaction of European particle RT hubs to manage the healthcare crisis. Considering the new waves and virus variants, the vaccination campaign will hopefully reduce the oncological impacts and consequences of the prolonged outbreak

Results of a survey on elderly head and neck cancer patients on behalf of the Italian Association of Radiotherapy and Clinical Oncology (AIRO)

Problem. Over the years, evidence-based data and technical improvements have consolidated the central role of radiation therapy (RT) in head and neck cancer (HNC) treatment, even in the elderly. This survey aimed to describe the management of the elderly HNC patients among Italian Radiation Oncology Departments (RODs) and provide possible suggestions for improvement. Method of study. An online survey based on 43 questions was sent to RODs via email. For each RODs, a radiation oncologist with expertise in HNC was invited to answer questions addressing his/her demographic data, ROD multidisciplinary unit (MU) organisation and ROD management policy in elderly HNC patients. Results. In total, 68 RODs answered, representing centres located in 16 Italian regions. MU was considered the core of HNC patient management in almost all the country. However, in many RODs, there was minimal access to a routinely comprehensive geriatric assessment at diagnosis. Most treatments were reported by respondents as curative (89% on average) and the preferred treatment technique was intensity modulated radiation therapy (IMRT). A considerable variation between RODs was found for RT target volumes. There was a relation between the specialist’s years of experience and type of concomitant systemic therapy prescribed. Conclusions. Substantial differences in elderly HNC management have been found, especially concerning patient clinical evaluation and target volume delineation. This survey shows the necessity to design a prospective national trial to provide a uniform treatment strategy and define an effective patient-centred approach

Psychological Factors Affecting the Willingness to Accept a Possible Tyrosine Kinase Inhibitor (TKI) Discontinuation in Chronic Myeloid Leukaemia (CML) Patients

Purpose: Patients with chronic myeloid leukemia (CML) who present a sustained deep molecular response (DMR) for a stable period of time might benefit from discontinuing tyrosine kinase inhibitors (TKIs). A significant number of patients seem able to reach this stage due to the availability of TKIs. However, many patients remain reluctant about TKI discontinuation and may refuse treatment interruption. The purpose of this study was to explore the clinical and psycho-cognitive factors that may influence the decision to discontinue TKI therapy, thereby gaining a better understanding of patients’ viewpoints on TKI discontinuation. Patients and Methods: One hundred and nineteen patients diagnosed with CML aged between 34 and 69 were enrolled (67 males and 52 females). Different clinical information and psycho-cognitive aspects such as attitude toward risk behaviours, risk preferences, need for cognitive closure, and tendency to resist to changes were assessed through the administration of a battery of questionnaires. Results: A higher tendency toward risk behaviours and the tendency to focus on possible gain in the short term rather than on losses might represent important predictors for the willingness to accept TKI discontinuation. Possible relapses following interruption of the therapy are the most common reason for concern. Furthermore, lower levels of resistance to change and having previously experienced the desire to interrupt the therapy might lead patients to accept a higher probability of relapse risk when facing such a decision. Conclusion: TKI discontinuation appears appealing and challenging at the same time for many CML patients, and different factors may influence this decision. Psychology plays a crucial role in assisting physician-patient communication and informed decisionmaking

A functional gene expression analysis in epithelial sinonasal cancer: Biology and clinical relevance behind three histological subtypes

Epithelial sinonasal cancers (SNCs) are rare diseases with overlapping morphological features and a dismal prognosis. We aimed to investigate the expression differences among the histological subtypes for discerning their molecular characteristics. We selected 47 SNCs: (i) 21 nonkeratinizing squamous cell carcinomas (NKSCCs), (ii) 13 sinonasal neuroendocrine cancers (SNECs), and (iii) 13 sinonasal undifferentiated cancers (SNUCs). Gene expression profiling was performed by DASL (cDNA-mediated annealing, selection, extension, and ligation) microarray analysis with internal validation by quantitative RT-PCR (RT-qPCR). Relevant molecular patterns were uncovered by sparse partial-least squares discriminant analysis (sPLS-DA), microenvironment cell type (xCell), CIBERSORT, and gene set enrichment (GSEA) analyses. The first two sPLS-DA components stratified samples by histological subtypes. xCell highlighted increased expression of immune components (CD8 + effector memory cells, in SNUC) and \u201cother cells\u201d: keratinocytes and neurons in NKSCC and SNEC, respectively. Pathway enrichment was observed in NKSCC (six gene sets, proliferation related), SNEC (one gene set, pancreatic \u3b2-cells), and SNUC (twenty gene sets, some of them immune-system related). Major neuroendocrine involvement was observed in all the SNEC samples. Our high-throughput analysis revealed a good diagnostic ability to differentiate NKSCC, SNEC, and SNUC, but indicated that the neuroendocrine pathway, typical and pathognomonic of SNEC is also present at lower expression levels in the other two histological subtypes. The different and specific profiles may be exploited for elucidating their biology and could help to identify prognostic and therapeutic opportunities

Long-term outcome of re-irradiation for recurrent or second primary head and neck cancer: A multi-institutional study of AIRO-Head and Neck working group

Background To report the long-term outcome of patients undergoing re-irradiation (re-RT) for a recurrent or second primary head and neck cancer (RSPHNCs) in seven Italian tertiary centers, while testing the Multi-Institution Reirradation (MIRI) recursive partitioning analysis (RPA) recently published. Methods We retrospectively analyzed 159 patients. Prognostic factors for overall survival (OS) selected by a random forest model were included in a multivariable Cox analysis. To externally validate MIRI RPA, we estimated the Kaplan-Meier group-stratified OS curves for the whole population. Results Five-year OS was 43.5% (median follow-up: 49.9 months). Nasopharyngeal site, no organ dysfunction, and re-RT volume <36 cm(3) were independent factors for better OS. By applying the MIRI RPA to our cohort, a Harrell C-Index of 0.526 was found indicating poor discriminative ability. Conclusion Our data reinforce the survival benefit of Re-RT for selected patients with RSPHNC. MIRI RPA was not validated in our population

Quality of life changes over time and predictors in a large head and neck patients' cohort: secondary analysis from an Italian multi-center longitudinal, prospective, observational study-a study of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) head and neck working group

Purpose: The present study examined the longitudinal trajectories, through hierarchical modeling, of quality of life among patients with head and neck cancer, specifically symptoms burden, during radiotherapy, and in the follow-up period (1, 3, 6, and 12&nbsp;months after completion of radiotherapy), through the M.D. Anderson Symptom Inventory Head and Neck questionnaire, formed by three factors. Furthermore, analyses were conducted controlling for socio-demographic as well as clinical characteristics. Methods: Multi-level mixed-effects linear regression was used to estimate the association between quality of life and time, age, gender, household, educational level, employment status, ECOG performance status, human papilloma virus (HPV) status, surgery, chemotherapy, alcohol intake, and smoking. Results: Among the 166 participants, time resulted to be a predictor of all the three questionnaire factors, namely, general and specific related symptoms and interference with daily life. Moreover, regarding symptom interference with daily activities factor, HPV-positive status played a significant role. Considering only HPV-negative patients, only time predicted patients' quality of life. Differently, among HPV-positive patients, other variables, such as gender, educational level, alcohol use, surgery, age at diagnosis, employment status, and ECOG status, resulted significant. Conclusion: It was evident that quality of life of patients with head and neck cancer declined during RT, whereas it slowly improved after ending treatment. Our results clarified the role of some socio-demographic and clinical variables, for instance, HPV, which would allow to develop treatments tailored to each patient