Nivolumab Switch Maintenance Therapy After Tyrosine Kinase Inhibitor Induction in Metastatic Renal Cell Carcinoma: A Randomized Clinical Trial by the Interdisciplinary Working Group on Renal Tumors of the German Cancer Society (NIVOSWITCH; AIO-NZK-0116ass).

BACKGROUND: The role of immune checkpoint inhibitor (ICI) maintenance therapy in metastatic renal cell carcinoma (mRCC) is undefined. OBJECTIVE: To determine whether switch maintenance therapy with nivolumab improves clinical outcomes in patients with mRCC with tyrosine kinase inhibitor (TKI) sensitivity. DESIGN, SETTING, AND PARTICIPANTS: This open-label phase 2 trial randomized patients with a partial response or stable disease after 10-12-wk TKI induction therapy to either TKI or nivolumab maintenance. Key inclusion criteria were measurable disease, clear cell histology, Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2, and adequate organ function. INTERVENTION: Intravenous nivolumab 8 × 240 mg every 2 wk, followed by 480 mg every 4 wk or sunitinib 50 mg (4-2 regimen) or pazopanib 800 mg once daily orally. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: The primary endpoint was overall survival (OS). Secondary endpoints were the objective response rate (ORR; Response Evaluation Criteria in Solid Tumors v1.1), progression-free survival (PFS), safety (Common Terminology Criteria for Adverse Events v4.03), and patient-reported outcomes (Functional Assessment of Cancer Therapy Kidney Symptom Index). The Kaplan-Meier method, two-sided log-rank tests, and Cox regression models were used for statistical analysis. RESULTS AND LIMITATIONS: Maintenance therapy was nivolumab for 25 patients (51.0%) and TKI for 24 (48.9%). The median age was 65 yr (range 35-79). Nine patients (18.4%) were female, 31 (63.3%) had ECOG PS of 0, and 15 (30.6%) had favorable risk. OS data are immature (17 deaths, 34.7%). The ORR was 20.0% (n = 5) for nivolumab and 52.2% (n = 12) for TKI. PFS was worse with nivolumab (hazard ratio 2.57, 95% confidence interval 1.36-4.89; p = 0.003). Grade ≥3 adverse events occurred in 14 patients (56.0%) with nivolumab and 17 (70.8%) with TKI. A major limitation is early termination of our study. CONCLUSIONS: TKI treatment achieved superior ORR and PFS in comparison to nivolumab maintenance therapy. Our data do not indicate a role for nivolumab switch maintenance in mRCC. PATIENT SUMMARY: Patients with metastatic kidney cancer who experienced a tumor response or disease stabilization after a short period of targeted treatment with a tyrosine kinase inhibitor did not benefit from a switch to the immunotherapy drug nivolumab. Patients who continued their original treatment achieved better responses and a longer time without disease progression. This trial is registered on EudraCT as 2016-002170-13 and on ClinicalTrials.gov as NCT02959554.

Patient, nurse, and physician preferences: final results of the CONVENIENCE study evaluating pegfilgrastim prophylaxis via pre-filled syringe or on-body injector in cancer patients.

PURPOSE: The on-body injector (OBI) automatically delivers pegfilgrastim the day after chemotherapy (CTx), thus eliminating the need of return visits to the medical office for guideline-compliant pegfilgrastim administration. The CONVENIENCE study aimed to evaluate patient, nurse, and physician preferences as well as health economics for pegfilgrastim administration either with OBI or manually using a pre-filled syringe (PS). METHODS: Patients with early breast cancer, receiving two or three weekly anthracycline/cyclophosphamide or three weekly taxane-based CTx, and patients with Non-Hodgkin lymphoma (NHL) receiving first-line R-CHOP-14 or -21 were randomized 1:1 to receive both pegfilgrastim application forms for four consecutive CTx cycles in an alternating sequence starting either with OBI or PS. Primary endpoint was patient preference, assessed by questionnaires. RESULTS: A total of 308 patients were evaluable in the per-protocol analysis. Patients slightly preferred OBI over PS (OBI, n = 133, 43.2%; vs. PS, n = 111, 36.0%; p-value = 0.159), while study nurses slightly preferred PS (n = 19, 46.3%) over OBI (n = 18, 43.9%) and physicians clearly preferred PS (n = 24, 58.8%) over OBI (n = 15, 36.6%). Among patients with preference for OBI, saving of time was their major reason for preference (53.4%). Pegfilgrastim was administered 24-72 h after each CTx cycle in 97.6% of OBI and 63.1% of PS applications. CONCLUSION: The OBI was slightly preferred by patients and saving time was the major reason for their preference. PS was physicians' most preferable choice and slightly preferred by nurses. Using OBI, pegfilgrastim was almost always administered within the time period recommended by current guidelines, while it was often not applied as specified using PS. TRIAL REGISTRATION: No: ClinicalTrials.gov No. NCT03619993. Registered on June 25, 2018.

What is adolescent polycystic ovary syndrome?

The diagnostic criteria for adolescent polycystic ovary syndrome (PCOS) has been derived from adult criteria, which makes diagnosis challenging as criteria include normal physiological events that occur during puberty such as acne, hirsutism, menstrual irregularities, high androgen levels and polycystic ovarian morphology on pelvic ultrasound. The only criteria that applies from the adult criteria is exclusion of other conditions that mimic PCOS. Clinical findings consistent with hyperandrogenaemia during adolescence include inflammatory acne, hirsutism, alopecia and/or menstrual irregularities, which are severe and present 2 years after menarche. The measurement of androgen levels during adolescence should take into account age, puberty, type of androgen measured, assay used and diurnal rhythm. Multiple measurements are useful to demonstrate hyperandrogenaemia. The combination, severity and persistence of the hyperandrogenic symptoms and hyperandrogenaemia in girls 2 years or more post-menarche support the diagnosis of adolescent PCOS. Adolescent girls with these findings should be followed up into adulthood.

Laboratory performance of sweat conductivity for the screening of cystic fibrosis.

BACKGROUND: There are several complementary English-language guidelines for the performance of the sweat chloride test. These guidelines also incorporate information for the collection of conductivity samples. However, recommendations for the measurement and reporting of sweat conductivity are less clear than for sweat chloride. The aim of the study was to develop an understanding of the testing and reporting practices of sweat conductivity in Australasian laboratories. METHODS: A survey specifically directed at conductivity testing was sent to the 12 laboratories registered with the Royal College of Pathologists of Australasia Quality Assurance Programs. RESULTS: Nine (75%) laboratories participated in the survey, seven of whom used Wescor Macroduct® for collecting sweat and the Wescor SWEAT·CHEK™ for conductivity testing, and the remaining two used the Wescor Nanoduct®. There was considerable variation in frequency and staffing for this test. Likewise, criteria about which patients it was inappropriate to test, definitions of adequate collection sweat rate, cutoffs and actions recommended on the basis of the result showed variations between laboratories. CONCLUSIONS: Variations in sweat conductivity testing and reporting reflect many of the same issues that were revealed in sweat chloride test audits and have the potential to lead to uncertainty about the result and the proper action in response to the result. We recommend that sweat testing guidelines should include clearer statements about the use of sweat conductivity.

Molecular cytogenetic monitoring from CD34+ peripheral blood cells in myelodysplastic syndromes: first results from a prospective multicenter German diagnostic study.

The gold standard of cytogenetic analysis in myelodysplastic syndromes (MDS) is conventional chromosome banding (CCB) analysis of bone marrow (BM) metaphases. Most aberrations can also be detected by fluorescence-in situ-hybridization (FISH). For this prospective multicenter German diagnostic study (www.clinicaltrials.gov: #NCT01355913) 360 patients, as yet, were followed up to 3 years by sequential FISH analyses of immunomagnetically enriched CD34+ peripheral blood (PB) cells using comprehensive FISH probe panels, resulting in a total number of 19,516 FISH analyses. We demonstrate that CD34+ PB FISH correlates significantly with CCB analysis and represents a feasible method for a reliable non-invasive cytogenetic monitoring from PB.

The delineation of target volumes for radiotherapy of lung cancer patients.

PURPOSE: Differences in the delineation of the gross target volume (GTV) and planning target volume (PTV) in patients with non-small-cell lung cancer are considerable. The focus of this work is on the analysis of observer-related reasons while controlling for other variables. METHODS: In three consecutive patients, eighteen physicians from fourteen different departments delineated the GTV and PTV in CT-slices using a detailed instruction for target delineation. Differences in the volumes, the delineated anatomic lymph node compartments and differences in every delineated pixel of the contoured volumes in the CT-slices (pixel-by-pixel-analysis) were evaluated for different groups: ten radiation oncologists from ten departments (ROs), four haematologic oncologists and chest physicians from four departments (HOs) and five radiation oncologists from one department (RO1D). RESULTS: Agreement (overlap > or = 70% of the contoured pixels) for the GTV and PTV delineation was found in 16.3% and 23.7% (ROs), 30.4% and 38.6% (HOs) and 32.8% and 35.9% (RO1D), respectively. CONCLUSION: A large interobserver variability in the PTV and much more in the GTV delineation were observed in spite of a detailed instruction for delineation. The variability was smallest for group ROID where due to repeated discussions and uniform teaching a better agreement was achieved.

Secondary leukaemia after cure for locally advanced NSCLC: alkylating type secondary leukaemia after induction therapy with docetaxel and carboplatin for NSCLC IIIB.

Specific cytogenetic alterations in t-MDS and t-AML are associated with different chemotherapeutic agents, such as loss of chromosomal material from #5 and #7 with alkylators. No data have been published on secondary leukemias following the taxane docetaxel. We report a patient, who being in long-term remission after docetaxel-based induction chemotherapy with docetaxel and carboplatin, surgery and adjuvant radiotherapy for non-small cell lung cancer stage IIIB, developed a t-MDS and subsequently a t-AML 40 months after start of therapy. The t-MDS was characterised by a complex aberrant karyotype including monosomy #13 and partial monosomies of #5 and #7. This is the first report in the literature of t-MDS after docetaxel chemo-radiotherapy, implicating a possible association of docetaxel with alkylator type t-MDS and t-AML. The case will be discussed in the context of a review of the current literature.