Predictive factors for severe toxicity of sunitinib in unselected patients with advanced renal cell cancer

Sunitinib has been registered for the treatment of advanced renal cell cancer (RCC). As patient inclusion was highly selective in previous studies, experience with sunitinib in general oncological practice remains to be reported. We determined the efficacy and safety of sunitinib in patients with advanced RCC included in an expanded access programme. ECOG performance status >1, histology other than clear cell and presence of brain metastases were no exclusion criteria. Eighty-two patients were treated: 23% reached a partial response, 50% had stable disease, 20% progressed and six patients were not evaluable. Median progression-free survival (PFS) was 9 months and median overall survival (OS) was 15 months. Importantly, 47 patients (57%) needed a dose reduction, 35 (43%) because of treatment-related adverse events, 10 (12%) because of continuous dosing, and two because of both. Stomatitis, fatigue, hand–foot syndrome and a combination of grade 1–2 adverse events were the most frequent reasons for dose reduction. In 40 patients (49%), there was severe toxicity, defined as dose reduction or permanent discontinuation, which was highly correlated with low body surface area, high age and female gender. On the basis of age and gender, a model was developed that could predict the probability of severe toxicity

Symmetry breaking in crossed magnetic and electric fields

We present the first observations of cylindrical symmetry breaking in highly excited diamagnetic hydrogen with a small crossed electric field, and we give a semiclassical interpretation of this effect. As the small perpendicular electric field is added, the recurrence strengths of closed orbits decrease smoothly to a minimum, and revive again. This phenomenon, caused by interference among the electron waves that return to the nucleus, can be computed from the azimuthal dependence of the classical closed orbits.Comment: 4 page REVTeX file including 5 postscript files (using psfig) Accepted for publication in Physical Review Letters. Difference from earlier preprint: we have discovered the cause of the earlier apparent discrepancy between experiment and theory and now achieve excellent agreemen

Clinical evaluation of the clinicopathologic and gene expression profile (CP-GEP) in patients with melanoma eligible for sentinel lymph node biopsy:A multicenter prospective Dutch study

Sentinel lymph node biopsy (SLNB) is recommended for patients with &gt;pT1b cutaneous melanoma, and should be considered and discussed with patients diagnosed with pT1b cutaneous melanoma for the purpose of staging, prognostication and determining eligibility for adjuvant therapy. Previously, the clinicopathologic and gene expression profile (CP-GEP, Merlin Assay®) model was developed to identify patients who can forgo SLNB because of a low risk for sentinel node metastasis. The aim of this study was to evaluate the clinical use and implementation of the CP-GEP model in a prospective multicenter study in the Netherlands. Both test performance and feasibility for clinical implementation were assessed in 260 patients with T1-T4 melanoma. The CP-GEP model demonstrated an overall negative predictive value of 96.7% and positive predictive value of 23.7%, with a potential SLNB reduction rate of 42.2% in patients with T1-T3 melanoma. With a median time of 16 days from initiation to return of test results, there was sufficient time left before the SLNB was performed. Based on these outcomes, the model may support clinical decision-making to identify patients who can forgo SLNB in clinical practice.</p

From decision to reflection:understanding the experiences and unmet care needs of patients treated with immunotherapy for melanoma in the adjuvant or metastatic setting

BACKGROUND: Despite increased use of immune checkpoint inhibitors (ICIs) in patients with advanced melanoma, little is known about patient experiences during this treatment. This study aimed to gain an in-depth understanding of experiences and unmet care needs of patients treated in the adjuvant or metastatic setting for advanced melanoma regarding their ICI treatment trajectory.METHODS:Interviews and focus groups were conducted among 35 patients treated with ICIs in the adjuvant setting for completely resected stage III (n = 14), or in the metastatic setting for irresectable stage IV (n = 21) melanoma. A thorough thematic content analysis was conducted.RESULTS: Three main themes were identified. When (1) dealing with uncertainty in the decision-making process, adjuvant patients explored the pros and cons, whereas metastatic patients considered immunotherapy their only viable option. Both groups expressed the need for additional guidance. In (2) navigating the immunotherapy course, both perceived the trajectory as intense, experienced a major impact on their and their (close) relatives' lives, and felt the need to (re)gain control. When (3) looking back on the immunotherapy experience, metastatic patients generally felt relieved, while among adjuvant patients, feelings of doubt regarding their choice for ICIs were also reported.CONCLUSIONS: ICI treatment is perceived as intensive for both patient groups, facing both comparable and distinct challenges throughout the treatment trajectory, underscoring the need for stage-specific, individualised guidance. Options regarding flexible follow-ups, low-threshold contact and psychosocial support throughout the treatment trajectory should be explored.</p

From decision to reflection:understanding the experiences and unmet care needs of patients treated with immunotherapy for melanoma in the adjuvant or metastatic setting

BACKGROUND: Despite increased use of immune checkpoint inhibitors (ICIs) in patients with advanced melanoma, little is known about patient experiences during this treatment. This study aimed to gain an in-depth understanding of experiences and unmet care needs of patients treated in the adjuvant or metastatic setting for advanced melanoma regarding their ICI treatment trajectory.METHODS:Interviews and focus groups were conducted among 35 patients treated with ICIs in the adjuvant setting for completely resected stage III (n = 14), or in the metastatic setting for irresectable stage IV (n = 21) melanoma. A thorough thematic content analysis was conducted.RESULTS: Three main themes were identified. When (1) dealing with uncertainty in the decision-making process, adjuvant patients explored the pros and cons, whereas metastatic patients considered immunotherapy their only viable option. Both groups expressed the need for additional guidance. In (2) navigating the immunotherapy course, both perceived the trajectory as intense, experienced a major impact on their and their (close) relatives' lives, and felt the need to (re)gain control. When (3) looking back on the immunotherapy experience, metastatic patients generally felt relieved, while among adjuvant patients, feelings of doubt regarding their choice for ICIs were also reported.CONCLUSIONS: ICI treatment is perceived as intensive for both patient groups, facing both comparable and distinct challenges throughout the treatment trajectory, underscoring the need for stage-specific, individualised guidance. Options regarding flexible follow-ups, low-threshold contact and psychosocial support throughout the treatment trajectory should be explored.</p

Bichromatic electromagnetically induced transparency in cold rubidium atoms

In a three-level atomic system coupled by two equal-amplitude laser fields with a frequency separation 2$\delta$, a weak probe field exhibits a multiple-peaked absorption spectrum with a constant peak separation $\delta$. The corresponding probe dispersion exhibits steep normal dispersion near the minimum absorption between the multiple absorption peaks, which leads to simultaneous slow group velocities for probe photons at multiple frequencies separated by $\delta$. We report an experimental study in such a bichromatically coupled three-level $\Lambda$ system in cold $^{87}$Rb atoms. The multiple-peaked probe absorption spectra under various experimental conditions have been observed and compared with the theoretical calculations.Comment: RevTex, 4 pages, 6 figures, Email address: [email protected]

Cyber Security: China and Russia\u27s Erosion of 21st Century United States\u27 Hegemony

With Russia and China emerging as challengers to U.S. hegemony, the use of cyber warfare could tilt the current balance of power in either of their favors. Using various methods, hackers can acquire sensitive information and destroy online infrastructures. In the development of cyber warfare, China has become a seasoned veteran with computer virus operations dating back to 199714. Russia has emerged as a cyber aggressor, as seen in Russia’s cyber attacks on several countries in the last decade. This paper argues that, with the growth of foreign cyber technology, the probability of cyberspace being used as a military front by state or non-state actors against the United States increases