Effect of Treatment of Residual Disease After Immunotherapy-Based Combinations on Complete Response Rate of Patients With Metastatic Renal Cell Carcinomas.

INTRODUCTION: Immune checkpoint inhibitor (ICI)-based combinations have revolutionized the management of first-line metastatic renal cell carcinoma (mRCC) by improving patient survival. Large phase 3 randomized trials assessing ICI-based combinations have reported complete response (CR) rates of 10% to 18% in the first-line setting. However, there is a scarcity of data about the effect of treatment of residual disease regarding CR rates improvement. MATERIALS AND METHODS: We included retrospectively all consecutive mRCC patients treated in first-line setting at the Institut de Cancérologie Strasbourg Europe with an ICI-based combination involving ICI or TKI, either alone or with added local treatment of residual disease. Patients were characterized according to IMDC risk. Radiologic response was defined according to RECIST v1.1. RESULTS: We enrolled 80 mRCC patients treated with ICI-based combinations between May 2015 and May 2022. The median age was 63 years. Regarding IMDC risk, there were 12 favourable (15%), 50 intermediate (63%), and 18 poor-risk (22%) patients. Forty-seven patients (59%) received ICI + ICI, 24 (30%) received ICI + TKI, and 9 (11%) received another ICI-based therapy. In total, 8 achieved CR (10%), 36 patients (45%) achieved partial response, 23 (29%) achieved stable disease and 12 achieved progressive disease (15%) as the best response with systemic therapy alone. By adding local treatment of residual disease, 11 additional patients (14%) achieved radiological NED. Residual disease resected sites included kidney (n = 6), lymph nodes (n = 5), lung metastases (n = 2) and liver metastases (n = 1). CONCLUSIONS: The resection of residual disease after first-line ICI-based therapy is associated with improved CR rate (CR + NED) in patients with mRCC. These results need to be validated in prospective trial. PATIENT SUMMARY: In recent years, the advent of immunotherapy has radically changed the management of patients with metastatic kidney cancer. Approximately 10% to 18% of these patients using immune checkpoint inhibitor (ICI)-based combinations no longer have detectable disease on CT scans (complete response). There are currently few data on the use of treatment of residual disease to increase the number of patients in complete response. In this retrospective study, the complete response rate with ICI-based treatment was 10%. When local treatment was added, the number of patients with a complete response increased to 24%. This strategy could increase the number of patients with a prolonged complete response in the future.

[Percutaneous MR-guided prostate cancer cryoablation: Predictive factors and oncologic outcomes]. / Cryothérapie totale de la prostate sous IRM par voie périnéale : résultats carcinologiques et facteurs prédictifs.

OBJECTIVE: To determine the pejorative predictive factors on oncologic outcomes of percutaneous MR-guided whole gland prostate cancer cryoablation (CA). METHODS: Medical records of patients treated from 2009 to 2012, to assess medium-term oncologic outcomes, were reviewed. Prostate biopsies were performed in local recurrence suspicion (biochemical failure, MR follow-up failure). RESULTS: Among 18 patients, mean age of 72.6 (61-78), 2 (11 %) and 7 (38.9 %) biological and reported biopsy-proven local recurrence respectively with our initial technic of CA. Mean follow-up and recurrence were 56.3 (±21.7) and 20.7 (±13.9) months respectively. A previous treatment of prostate cancer (P=0.5), pre-treatment PSA (P=0.2), pre-treatment Gleason/ISUP score (P=0.4), nadir PSA post-CA (P=0.22) were not associated with recurrence. Bilateral positive cores appears as a pejorative predictive factor (P=0.04). However mean pre-treatment positive cores percentage, 25 (±16.5) in responding patients versus 40.7 (±25.2) in case of recurrence, and maximum percentage of cancer extent in each positive core, 10.6 (±9.3) in responding patients versus 18.7 (±16.5) in case of recurrence, seemed associated with local recurrence after prostate CA but our analysis wasn't able to find a difference (P=0.09 and P=0.3 respectively) due to a lack of power. CONCLUSION: Bilateral positive cores appears as a pejorative predictive factor. In our experience, important tumor volume seem to be a pejorative predictive factor for oncologic outcomes after PCA whereas treatment, PSA, Gleason/ISUP score, nadir PSA are not. LEVEL OF EVIDENCE: 4.

[Temporary urethral stents changes as an alternative treatment for neurological bladder]. / Les changements itératifs de prothèse urétrale trans-sphinctérienne chez le patient neurologique : une alternative à la sphinctérotomie ?

BACKGROUND: Patients with detrusor-sphincter dysynergia (DSD) who are unable to perform self-catheterisation can benefit from an endoscopic treatment. We chose regular urethral stent changes as an alternative to sphincterotomy in this kind of patients. The purpose of this study is to show that temporary urethral stents changes represent a treatment option with a reasonable morbidity for patients with DSD. METHODS: We retrospectively reviewed patients in our center who had been treated with urethral stents from April 2005 to September 2017. The stent changes were performed every 12 to 18 months depending on urethrovesical fibroscopy findings. The primary endpoint was treatment continuation. RESULTS: A total of 44 patients were enrolled in our study and the average follow-up duration was 46 months [18.5-53.25]. Primary treatment failure was seen in 14 (32%) patients mainly due to problems related to equipment (n=3) and urinary retention (n=2). Four patients died before their first stent change. The treatment was successful in 30 (68%) patients, of whom 10 (33%) subsequently adopted a voiding mode change. We lost sight of 5 patients (11%) during follow-up. The main complications were urinary retention (29%), urinary tract infections (27%) and stent migration (18%). Fifteen (34%) experienced grade III-IV complications. CONCLUSIONS: Regular urethral stent changes represent an alternative treatment option for patients with DSD but with a significant morbidity. LEVEL OF EVIDENCE: 4.

Signal processing and calibration procedures for in situ diode-laser absorption spectroscopy.

Gas analyzers based on tunable diode-laser spectroscopy (TDLS) provide high sensitivity, fast response and highly specific in situ measurements of several atmospheric trace gases simultaneously. Under optimum conditions even a shot noise limited performance can be obtained. For field applications outside the laboratory practical limitations are important. At ambient mixing ratios below a few parts-per-billion spectrometers become more and more sensitive towards noise, interference, drift effects and background changes associated with low level signals. It is the purpose of this review to address some of the problems which are encountered at these low levels and to describe a signal processing strategy for trace gas monitoring and a concept for in situ system calibration applicable for tunable diode-laser spectroscopy. To meet the requirement of quality assurance for field measurements and monitoring applications, procedures to check the linearity according to International Standard Organization regulations are described and some measurements of calibration functions are presented and discussed.

Spectroscopic gas analyzers based on indium-phosphide, antimonide and lead-salt diode-lasers.

Currently available semiconductor lasers for spectroscopy in the near- and mid-infrared region based on direct band-to-band transitions as gallium-arsenide, indium-phosphide, antimonides and lead-salt containing compounds will be discussed together with the main features of different tunable diode-laser absorption spectrometers for trace gas analysis. Measurements of atmospheric carbon dioxide with a room-temperature 2 microm indium-phosphide laser, applications of antimonide lasers for methane and formaldehyde sensing in the 3-4 microm range and a fast chemical sensor for methane flux measurements based on lead-salt diode-lasers operating near 7.8 microm will be presented.

Fast chemical sensor for eddy-correlation measurements of methane emissions from rice paddy fields.

A high-frequency-modulation spectrometer with a lead-salt diode laser operating in the nu(4) band of CH(4) at 7.8 mum was used as a fast chemical sensor to measure ambient methane concentrations of 2 ppmv (parts in 10(6) volume-mixing ratio) with a time resolution of 10 Hz for micrometeorological flux measurements. To assess the quality of the data on methane emissions from rice paddy fields, we compared eddy-correlation measurements with simultaneously recorded emission data from the state-of-the-art closed-chamber technique and showed that the closed-chamber measurements were 60%-90% higher than were the eddy-correlation measurements during the campaign. This outcome demonstrates that diode-laser spectroscopy is a valuable tool for quality assurance.

Application of antimonide lasers for gas sensing in the 3-4-microm range.

Antimonide semiconductor laser devices designed for continuous-wave emission in the 3-4-microm spectral range have been investigated with respect to spectroscopic applications. Representative data on the mode structure, output power, noise characteristics, far-field pattern, and modulation response are presented. Selected laser devices have been applied for methane (CH(4)) and formaldehyde (HCHO) measurements by use of a high-frequency modulated diode laser spectrometer. From an Allan variance analysis of experimental data a detection limit for HCHO of 120 pptv (where 1 pptv = 10(-12) volume mixing ratio) with a 40-s integration time and for CH(4) of 2 ppbv (where 1 ppbv = 10(-9) volume mixing ratio) with 20-s integration time were determined. The results show that, for selected gases, InAsSb lasers can be an alternative to lead-salt diode lasers.

Signal-to-noise ratio analysis in laser absorption spectrometers using optical multipass cells.

In high resolution absorption spectrometers with conventional light sources, the signal-to-noise ratio (SNR) is usually limited by the thermal noise level of the detector-preamplifier combination, which is independent of the light source power. However, the noise in many laser absorption spectrometers is dominated by the excess or shot noise which is dependent on the transmitted laser power, and which in turn is dependent on the number of reflections in a multipass cell. The optimum absorption path length for a high frequency modulated (FM) and a conventional wavelength modulated (WM) diode laser absorption spectrometer is investigated in this paper. The major result is that, due to the power attenuation by the multipass cell, the best SNR of a shot noise limited FM spectrometer is achieved at substantially shorter absorption paths, when compared with the excess noise limited WM spectrometer. This finding implies that the implementation of the FM technique in absorption spectrometers with multipasscells can improve the SNR only by 1 order of magnitude. Although desirable, this is substantially less than the improvement of 2 orders of magnitude expected in quantum limited conditions with a single pass cell.

Wideband noise characteristics of a lead-salt diode laser: possibility of quantum noise limited TDLAS performance.

The wideband noise characteristics of a PbEuSe molecular beam epitaxy diode laser have been measured up to 500 MHz. The cutoff of the frequency dependent (1/f type) laser noise contribution was found to be 170 MHz for this particular laser. Above this cutoff frequency the photon shot noise dominates, as was demonstrated. A noise reduction of more than 2 orders of magnitude was observed in the shot noise limited domain when compared with the 1/f noise dominated region below 1 MHz. This finding indicates that a similar 2 orders of magnitude sensitivity improvement can be achieved in tunable diode laser absorption spectroscopy when frequency modulation techniques are applied instead of the more conventional derivative modulation below 1 MHz.

[Perinatal mortality and asphyxia in premature babies (author's transl)]. / Perinatale Mortalität und Atemnotsyndrom bei "Frühgeborenen"

The aim of the present investigation was to study the influence of O2-ventilation, blind buffer therapy with Na-bicarbonate, late cord clamping and infusion of low molculare weight dextran on morbidity of Respiratory-Distress-Syndrom (RDS) and mortality during the first week in infants with a birthweight of 2500 g and less. The charts of 536 infants were studied. There were 481 life birth and 55 stillbirth (10.2%). In 185 infants the pH and Base-excess in the umbilical arterial blood was meassured. The infants born in 1969--1971 were compaired with them born in 1972--1973. In 52% of the "premature infants" the pH was 7.25 U and lower and in 90% of the Base-Excess was --4.5 meq/l and more. The perinatal mortality (PM) was 30% and 13% (P less than 0.01) resp. There was a correlation to the birthweight. The decrease of the PM was related to the fall in mortality of infant during the first week: 21% and 4% resp. Here too, there was a correlation to birthweight and gestational age. The morbidity in RDS: 20.6% and 10.0% (P less than 0.01) and mortality following RDS: 79.3% and 35.0% resp. (P less than 0.01) was also low in 1972--1973. The results permit us to conclude that it is of great importance to correct fetal acidosis immediately after birth to prevent irreversible alterations in the lung. It could also be of value to encrease cardiac output and lungperfusion by late cord clamping and injection of dextran 40. The other procedures belong to standard managment in handling an asphyxiated fetus.