Stereotactic radiosurgery of brain metastases: a retrospective study.

BACKGROUND: Single-fraction stereotactic radiosurgery (SRS) is an established standard for radiation therapy of brain metastases although recent developments indicate that multi-fractionated stereotactic radiotherapy (FSRT) results in lower radiation necrosis especially for larger metastases, and the same or even better local control in comparison to SRS. METHODS: Seventy-two patients with 111 brain metastases received SRS with a single dose of 18 Gy between September 2014 and December 2021. The dose prescription was either 18 Gy given to the enclosing 80% isodose with a normalization to Dmax = 100% of 22.5 Gy (part I) or 18 Gy = D98, while D0.03 cc of 21.6-22.5 Gy was accepted (part II). The study retrospectively evaluated local progression-free survival (LPFS), response on the first follow-up magnetic resonance imaging (MRI), and radiation necrosis. RESULTS: Melanoma brain metastases (n = 44) were the most frequent metastases. The median gross tumor volume (GTV) was 0.30 cm³ (IQR, 0.17-0.61). The median follow-up time of all patients was 50.8 months (IQR, 30.4-64.6). Median LPFS was 23.5 months (95%CI 17.2, 29.8). The overall LPFS rates at 12-, 18-, 24- and 30 months were 65.3%, 56.3%, 46.5%, and 38.8%. Brain metastases with radioresistant histology (melanoma, renal cell cancer, and sarcoma) showed a 12-month LPFS of 60.2%, whereas brain metastases with other histology had a 12-month LPFS of 70.1%. The response of brain metastases on first follow-up MRIs performed after a median time of 47 days (IQR, 40-63) was crucial for long-term local control and survival. Eight brain metastases (7.2%) developed radiation necrosis after a median time of 18.4 months (IQR, 9.4-26.5). In multivariate analyses, a GTV > 0.3 cm³ negatively affected LPFS (HR 2.229, 95%CI 1.172, 4.239). Melanoma, renal cell cancers, and sarcoma had a lower chance of LPFS in comparison to other cancer types (HR 2.330, 95%CI 1.155, 4.699). CONCLUSIONS: Our results indicate a reasonable 1-year local control of brain metastases with radiosensitive histology. Radioresistant metastases show a comparatively poor local control. Treatment refinements merit exploration to improve local control of brain metastases. TRIAL REGISTRATION: This study is retrospectively registered (ethics approval number 23-3451-104).

Fractionated stereotactic radiotherapy of brain metastases: results of a retrospective study.

BACKGROUND: Lasting local control of brain metastases following stereotactic radiotherapy is becoming increasingly relevant since systemic treatment constantly improves the prognosis of patients with extracranial metastases. METHODS: 73 patients with 103 brain metastases received hypofractionated stereotactic radiotherapy (FSRT) in 6 fractions of 5 Gy between January 2017 and December 2021 at the University Hospital Regensburg, Germany. The study retrospectively evaluated local progression free survival (LPFS), overall survival (OS) and distant brain progression free survival (DPFS) of patients without prior radiotherapy of the brain. Response rate and brain radiation necrosis were reported. Cox proportional hazard models evaluated prognostic factors of OS and LPFS. RESULTS: The median patient age was 61.0 years (Interquartile range, IQR 51.0, 67.5). The most common tumor types were malignant melanoma (34.2%) and non-small cell lung adenocarcinoma (26.0%). The median gross tumor volume (GTV) was 0.9 cm³ (IQR 0.4, 3.6). The median follow-up time of all patients was 36.3 months (95%CI 29.1, 43.4). The median OS was 17.4 months (95%CI 9.9, 24.9). Overall survival rates at 6-, 12-, 18-, 24-, and 30 months were 81.9%, 59.1%, 49.0%, 41.3%, and 37.2%, retrospectively. The mean LPFS was 38.1 months (95%CI 31.4, 44.9), while the median LPFS has not been reached. LPFS rates at 6-, 12-, 18-, 24- and 30 months were 78.9%, 68.7%, 64.3%, 61.6% and 58.7%, retrospectively. Median DPFS of all patients was 7.7 months (95%CI 6.1, 9.3). Six, 12-, 18-, 24- and 30 months DPFS rates were 62.1%, 36.3%, 31.1%, 24.8% and 21.7%. Five brain metastases (4.8%) developed brain radiation necrosis. In multivariate analysis, the number of brain metastases negatively affected LPFS. Non-melanoma and non-renal cell cancer was associated with a higher chance of LPFS in comparison to other cancer. A GTV > 1.5 cm³ translated into a higher risk of death compared to a GTV ≤ 1.5 cm³ and Karnofsky performance score was predictive of OS. CONCLUSIONS: FSRT in 6 fractions of 5 Gy seems to be an effective treatment with an acceptable local control for patients with brain metastases although melanoma and renal cell cancer seem to have a worse local control in comparison to other cancer. TRIAL REGISTRATION: This study is retrospectively registered.

Noninvasive treatment of two deeply invasive cutaneous squamous cell carcinomas of the midface located close to the orbits with intensity-modulated arc therapy: A case report.

Definitive radiotherapy is a curative and noninvasive treatment modality for cutaneous squamous cell carcinomas of the midface when surgery has an impact on function and cosmetics. Volumetric modulated arc therapy provides optimal dose coverage for complex-shaped tumors without compromising adjacent organs at risk.

Catalytic asymmetric synthesis of CF3-substituted tertiary propargylic alcohols via direct aldol reaction of α-N3 amide.

Organofluorine compounds are found in several important classes of chemicals, such as pharmaceuticals, agrochemicals, and functional materials. Chemists have been immensely interested in the development of methodologies for expeditious access to fluorine containing building blocks. In this study, we report a new method for the catalytic asymmetric synthesis of CF3-substituted tertiary propargylic alcohols with two contiguous stereogenic centers via the direct aldol reaction of an α-N3 amide to trifluoromethyl ketones. The key to the success of this method is the identification of a catalyst comprising Cu(ii)/chiral hydroxamic acid to promote the desired aldol reaction, constructing a tetrasubstituted carbon in a highly stereoselective fashion. Despite substantial prior advances in asymmetric catalysis, this class of catalysts has not been utilized for the formation of carbon-carbon bond-forming reactions. Our mechanistic study sheds light on the unique profile of this catalytic system, where the Cu(ii) complex plays a bifunctional role of serving as a Lewis acid and a Brønsted base. Furthermore, the densely functionalized aldol adducts undergo chemoselective transformations, affording a series of fluorine containing chiral building blocks with widespread application.

Direct Catalytic Asymmetric Mannich-Type Reaction of α-N3 Amide.

An α-N3 7-azaindoline amide serves as a latent enolate to directly engage in an asymmetric Mannich-type reaction with N-thiophosphinoyl imines by the action of a cooperative catalyst. The thus-obtained highly enantioenriched anti-adduct was transformed into ß-amino-α-azido acid in high yield by simple acidic treatment.

Direct Catalytic Asymmetric Aldol Reaction of an α-Azido Amide.

A direct aldol reaction of an α-azido 7-azaindolinylamide, promoted by a Cu-based cooperative catalyst, is documented. Aromatic aldehydes bearing an ortho substituent exhibited diastereodivergency depending on the nature of the chiral ligands used. Smooth reactions with ynals highlighted the broad substrate scope. A vicinal azido alcohol unit in the product allowed direct access to the corresponding aziridine and facile hydrolysis of the 7-azaindolinylamide moiety furnished enantioenriched ß-hydroxy-α-azido carboxylic acid derivatives.

A designed amide as an aldol donor in the direct catalytic asymmetric aldol reaction.

The direct catalytic asymmetric aldol reaction offers efficient access to ß-hydroxy carbonyl entities. Described is a robust direct catalytic asymmetric aldol reaction of α-sulfanyl 7-azaindolinylamide, thus affording both aromatic and aliphatic ß-hydroxy amides with high ee values. The design of this transformation features a cooperative interplay of a soft and a hard Lewis acid, which together facilitate the challenging chemoselective enolization by a hard Brønsted base.

Treatment of left sided breast cancer for a patient with funnel chest: volumetric-modulated arc therapy vs. 3D-CRT and intensity-modulated radiotherapy.

This case study presents a rare case of left-sided breast cancer in a patient with funnel chest, which is a technical challenge for radiation therapy planning. To identify the best treatment technique for this case, 3 techniques were compared: conventional tangential fields (3D conformal radiotherapy [3D-CRT]), intensity-modulated radiotherapy (IMRT), and volumetric-modulated arc therapy (VMAT). The plans were created for a SynergyS® (Elekta, Ltd, Crawley, UK) linear accelerator with a BeamModulator™ head and 6-MV photons. The planning system was Oncentra Masterplan® v3.3 SP1 (Nucletron BV, Veenendal, Netherlands). Calculations were performed with collapsed cone algorithm. Dose prescription was 50.4 Gy to the average of the planning target volume (PTV). PTV coverage and homogeneity was comparable for all techniques. VMAT allowed reducing dose to the ipsilateral organs at risk (OAR) and the contralateral breast compared with IMRT and 3D-CRT: The volume of the left lung receiving 20 Gy was 19.3% for VMAT, 26.1% for IMRT, and 32.4% for 3D-CRT. In the heart, a D(15%) of 9.7 Gy could be achieved with VMAT compared with 14 Gy for IMRT and 46 Gy for 3D-CRT. In the contralateral breast, D(15%) was 6.4 Gy for VMAT, 8.8 Gy for IMRT, and 10.2 Gy for 3D-CRT. In the contralateral lung, however, the lowest dose was achieved with 3D-CRT with D(10%) of 1.7 Gy for 3D-CRT, and 6.7 Gy for both IMRT and VMAT. The lowest number of monitor units (MU) per 1.8-Gy fraction was required by 3D-CRT (192 MU) followed by VMAT (518 MU) and IMRT (727 MU). Treatment time was similar for 3D-CRT (3 min) and VMAT (4 min) but substantially increased for IMRT (13 min). VMAT is considered the best treatment option for the presented case of a patient with funnel chest. It allows reducing dose in most OAR without compromising target coverage, keeping delivery time well below 5 minutes.

Commissioning of volumetric modulated arc therapy (VMAT) in a dual-vendor environment.

Methods and results for commissioning of the complete VMAT delivery chain are presented for the combination of Nucletron's Oncentra MasterPlan® v3.3 with Elekta's Mosaiq® v1.6 and SynergyS® linac. VMAT specific linac commissioning included determination of the size of the minimal dynamic leaf gap. Dosimetric validation of the complete treatment chain was performed using a 2D-ionization-chamber-array and showed excellent dosimetric results.

Efficient carboazidation of alkenes using a radical desulfonylative azide transfer process.

The radical-mediated carboazidation of terminal alkenes using electrophilic alkanesulfonyl azides is reported. A single reagent delivers the necessary electrophilic alkyl radical as well as the azido group, and good yields are obtained by using a moderate excess of the carboazidating reagent (1.5-2 equiv). Interestingly, in addition to the starting sulfonyl azide, this method requires only the use of a radical initiator, di-tert-butyldiazene. In terms of atom economy, this azide transfer reaction is close to ideal, as SO2 (1 equiv) is the only side product. The synthetic potential of this process has been demonstrated by a formal synthesis of the alkaloid lepadiformine C.

Application of volumetric modulated arc therapy (VMAT) in a dual-vendor environment.

BACKGROUND AND PURPOSE: The purpose of this study was to assess plan quality and treatment time achievable with the new VMAT optimization tool implemented in the treatment planning system Oncentra MasterPlan® as compared to IMRT for Elekta SynergyS® linear accelerators. MATERIALS AND METHODS: VMAT was implemented on a SynergyS® linear accelerator (Elekta Ltd., Crawley, UK) with Mosaiq® record and verify system (IMPAC Medical Systems, Sunnyvale, CA) and the treatment planning system Oncentra MasterPlan® (Nucletron BV, Veenendaal, the Netherlands). VMAT planning was conducted for three typical target types of prostate cancer, hypopharynx/larynx cancer and vertebral metastases, and compared to standard IMRT with respect to plan quality, number of monitor units (MU), and treatment time. RESULTS: For prostate cancer and vertebral metastases single arc VMAT led to similar plan quality as compared to IMRT. For treatment of the hypopharynx/larynx cancer, a second arc was necessary to achieve sufficient plan quality. Treatment time was reduced in all cases to 35% to 43% as compared to IMRT. Times required for optimization and dose calculation, however, increased by a factor of 5.0 to 6.8. CONCLUSION: Similar or improved plan quality can be achieved with VMAT as compared to IMRT at reduced treatment times but increased calculation times.