Drug-Related Pneumonitis During Mammalian Target of Rapamycin Inhibitor Therapy: Radiographic Pattern-Based Approach in Waldenström Macroglobulinemia as a Paradigm.

BACKGROUND: This study determined the frequency of drug-related pneumonitis during mammalian target of rapamycin (mTOR) inhibitor therapy in Waldenström macroglobulinemia patients and investigated the imaging characteristics and radiographic patterns of pneumonitis. MATERIALS AND METHODS: A total of 40 patients (23 men, 17 women; 43-84 years old) with Waldenström macroglobulinemia treated in 2 trials of the mTOR inhibitor everolimus were retrospectively studied. Chest computed tomography (CT) scans during therapy were reviewed for abnormalities suspicious for drug-related pneumonitis by the consensus of three radiologists, evaluating the extent, distributions, and specific findings. The radiographic patterns of pneumonitis were classified using the American Thoracic Society/European Respiratory Society classification of interstitial pneumonia. RESULTS: Drug-related pneumonitis was noted in 23 patients (58%). The median time from the initiation of therapy to the onset of pneumonitis was 5.7 months. Lower lungs were involved in all 23 patients, with a higher extent than in the other zones (p < .001). The distribution was peripheral and lower in 11 patients (48%) and mixed and multifocal in 10 (44%). The findings were bilateral in 20 patients (87%). Ground glass opacities (GGOs) and reticular opacities were present in all 23 patients, with consolidation in 12, traction bronchiectasis in 2, and centrilobular nodularity in 1. The pattern of pneumonitis was classified as cryptogenic organizing pneumonia (COP) in 16 (70%) and nonspecific interstitial pneumonia (NSIP) in 7 (30%), with overlapping features of COP and NSIP in 7 patients. CONCLUSION: Drug-related pneumonitis was noted on CT in 58% of Waldenström macroglobulinemia patients treated with mTOR inhibitor therapy. Most common findings were bilateral GGOs and reticular opacities, with or without consolidation, in peripheral and lower lungs, demonstrating COP and NSIP patterns. IMPLICATIONS FOR PRACTICE: The present study has demonstrated that drug-related pneumonitis during mammalian target of rapamycin (mTOR) inhibitor therapy is highly frequent, occurring in 58% of patients with Waldenström macroglobulinemia. The radiographic patterns of pneumonitis demonstrated cryptogenic organizing pneumonia and nonspecific interstitial pneumonia patterns, with overlapping features in 30% of the patients. The present study describes an initial attempt of a radiographic pattern-based approach to drug-related pneumonitis in the era of molecular targeting therapy, with a cohort of patients with Waldenström macroglobulinemia receiving mTOR inhibitor therapy as a paradigm, which might contribute to further understanding and in-depth interpretation of lung toxicity during novel cancer therapy.

Results of a phase 2 trial of the single-agent histone deacetylase inhibitor panobinostat in patients with relapsed/refractory Waldenström macroglobulinemia.

The present study aimed to determine the safety and activity of the histone deacetylase inhibitor panobinostat in patients with relapsed/refractory Waldenström macroglobulinemia (WM). Eligibility criteria included patients with relapsed/refractory WM with any number of prior therapies. Patients received panobinostat at 30 mg 3 times a week; 12 of 36 (33%) patients were enrolled at 25 mg dose. A total of 36 patients received therapy. The median age was 62 years (range, 47-80) and the median number of prior therapies was 3 (range, 1-8). All of the patients had received prior rituximab. Minimal response (MR) or better was achieved in 47% of patients (90% confidence interval [CI], 33-62), with 22% partial remissions and 25% MR. In addition, 18 (50%) patients achieved stable disease and none showed progression while on therapy. The median time to first response was 1.8 months (range, 1.7-3.2). The median progression-free survival was 6.6 months(90% CI, 5.5-14.8). Grade 3 and 4 toxicities included thrombocytopenia (67%), neutropenia (36%), anemia (28%), leukopenia (22%), and fatigue (11%). We conclude that panobinostat is an active therapeutic agent in patients with relapsed/ refractory WM. This study (www.clinicaltrials.gov identifier: NCT00936611) establishes a role for histone deacetylase inhibitors as an active class of therapeutic agents in WM.

Breast cancer and sexual function.

As the most common malignancy affecting women within the United States, breast cancer can bring about multiple physical and psychological challenges. Among the greatest challenges are those associated with female sexual function. Chemotherapy, endocrine therapy, surgeries and radiation can all have a large effect in altering a woman's sexual health and function. Sexual concerns result in significant emotional distress, including sadness/depression, issues related to personal appearance, stigma, and negative impacts on personal relationships. In this article, we discuss some of the specific challenges that present with each type of treatment and the socio-physical impact they have on survivorship. Among the most detrimental to sexual function, are the use of chemotherapy and endocrine therapy. Additionally, anatomical changes that transpire in patients who have undergone surgery or radiation therapy (RT), disrupt perceptions of body image. Here we will discuss and also review the contemporary literature to determine effective management and treatment of sexual dysfunction.