Previously, addition of isatuximab (Isa) to standard-of-care lenalidomide-bortezomib-dexamethasone (RVd) in transplant-eligible patients with newly diagnosed multiple myeloma in the GMMG-HD7 trial (ClinicalTrials.gov identifier: NCT03617731) resulted in a significant increase of minimal residual disease negativity (MRD-) rates after induction therapy. A total of 662 patients were randomly assigned to receive induction therapy with Isa-RVd (n = 331) or RVd (n = 329), followed by single or tandem autologous stem-cell transplant and second random assignment to maintenance with lenalidomide alone or Isa-lenalidomide. We report updated results for part 1 from first random assignment to post-transplant. As of January 31, 2024, MRD- rates continued to deepen after transplant (66% Isa-RVd v 48% RVd). Isa-RVd induction therapy significantly prolonged progression-free survival (PFS) compared with RVd regardless of maintenance therapy (hazard ratio, 0.70 [95% CI, 0.52 to 0.95]; P = .0184). Weighted risk set estimator analysis accounting for second random assignment followed by maintenance with only lenalidomide confirmed a statistically significant benefit for Isa-RVd followed by lenalidomide maintenance versus RVd followed by lenalidomide maintenance (stratified weighted log-rank test P = .016). In conclusion, after 18-week induction therapy followed by transplant without consolidation therapy, adding Isa to RVd resulted in a significant PFS benefit, regardless of maintenance strategy.
CARTITUDE-1 evaluated ciltacabtagene autoleucel (cilta-cel) in patients with heavily pretreated relapsed/refractory multiple myeloma (RRMM). We describe overall survival (OS), ≥5-year progression-free outcomes, associated biomarkers, and safety, with a median study follow-up of 61.3 months. For the 97 treated patients, median OS was 60.7 months (95% CI, 41.9 to not estimable). One third (32/97) of patients remain alive and progression-free for ≥5 years after a single cilta-cel infusion, without maintenance treatment. Twelve of these patients treated at a single center underwent serial minimal residual disease (MRD) and positron emission tomography-computed tomography assessments, and all (100%) were MRD-negative (at least 10−5 threshold) and imaging-negative at year 5 or later after cilta-cel. Baseline characteristics, including the presence of high-risk cytogenetics and extramedullary disease, were generally comparable for the 32 patients who were progression-free for ≥5 years versus patients who had progressive disease by year 5. A trend of lower baseline tumor burden, higher fraction of naïve T-cells in the cilta-cel drug product, higher T cell-to-neutrophil ratio, higher hemoglobin and platelets at baseline, and higher effector-to-target ratio were associated with ≥5-year progression-free status. The safety profile of cilta-cel remained consistent with previous reports. To our knowledge, our data provide the first evidence that cilta-cel is potentially curative in patients with RRMM.
Die MIDAS-Studie untersuchte bei neu diagnostiziertem, transplantationsfähigem Multiplen Myelom, ob eine an der messbaren Resterkrankung (MRD) orientierte Konsolidierungstherapie Vorteile bringt. Nach einer Induktionstherapie mit Isatuximab, Carfilzomib, Lenalidomid und Dexamethason (Isa-KRd) wurden die Patient*innen je nach MRD-Status (Sensitivität 10–⁵) randomisiert weiterbehandelt. MRD-negative Patient*innen erhielten entweder eine autologe Stammzelltransplantation (ASCT) plus zwei Zyklen Isa-KRd oder sechs Zyklen Isa-KRd ohne Transplantation. MRD-positive Patient*innen wurden entweder einer Tandem-ASCT oder einer einfachen ASCT plus zwei Zyklen Isa-KRd zugewiesen. Primärer Endpunkt war der Anteil an Patient*innen mit MRD-Negativität bei höherer Sensitivität (10–⁶) vor Beginn der Erhaltungstherapie. Bei MRD-negativen Patient*innen zeigte sich kein signifikanter Unterschied zwischen ASCT (86 %) und Isa-KRd (84 %). Auch bei MRD-positiven Patient*innen war der Unterschied zwischen Tandem-ASCT (32 %) und einfacher ASCT (40 %) nicht signifikant. Die Sicherheit war in allen Gruppen akzeptabel, ohne neue Signale.
Das multiple Myelom (MM) ist eine hämatologische Krebserkrankung, die durch die klonale Vermehrung von Plasmazellen im Knochenmark charakterisiert ist. Die derzeitige Behandlungslandschaft für das multiple Myelom umfasst eine Kombination aus Proteasom-Inhibitoren, Immunmodulatoren, monoklonalen Antikörpern und autologer Stammzelltransplantation. Diese hat in den letzten Jahren zu einer deutlichen Verbesserung der Überlebensraten geführt. Dennoch bleibt die Erkrankung – insbesondere in rezidivierenden und refraktären Fällen – eine klinische Herausforderung. In laufenden klinischen Studien werden neue Therapieoptionen evaluiert, darunter die Chimären-Antigenrezeptor-T-Zelltherapie, bispezifische Antikörper, Antikörper-Wirkstoff-Konjugate und neuartige Wirkstoffe wie Cereblon-E3-Ligase-Modulatoren. Diese Übersichtsarbeit fasst die wichtigsten diagnostischen Kriterien, prognostischen Merkmale und die Beurteilung des Ansprechens für MM zusammen und gibt einen Überblick über die aktuelle Behandlungssituation.
Einleitung: Myelomatöser Pleuraerguss (MPE) und Perikardbefall sind seltene Manifestationen des multiplen Myeloms (MM). Sie treten in weniger als 1 % der Fälle auf und waren historisch mit einer schlechten Prognose verbunden. Wir stellen einen einzigartigen Fall vor, bei dem beide dieser seltenen Manifestationen nacheinander in serösen Höhlen bei derselben Patientin auftraten. Dies verdeutlicht die sich weiterentwickelnde Behandlungslandschaft mit neuartigen, zielgerichteten Therapien. Falldarstellung: Eine 42-jährige asiatische Frau stellte sich mit Schmerzen und Schwellungen in der linken Schulter vor. Dies führte zur Diagnose eines IgG-Lambda-MM mit ausgedehnter extramedullärer Erkrankung. Nach einer anfänglichen partiellen Remission unter D-VRD-Therapie entwickelte sie einen MPE mit vollständigem Kollaps der linken Lunge. Nachdem eine Zweitlinientherapie mit KPD-PACE versagt hatte, erhielt sie Teclistamab und erreichte eine vollständige metabolische und morphologische Remission, die durch ein PET-CT dokumentiert wurde. Nach einer Remissionsdauer von zehn Monaten erlitt die Patientin einen Rückfall mit Perikardbeteiligung, der sich als Herztamponade manifestierte.
Background: Up to 65% of patients with chronic myeloid leukemia (CML) who are treated with imatinib do not achieve sustained deep molecular response, which is required to attempt treatment-free remission. Asciminib is the only approved BCR::ABL1 inhibitor that Specifically Targets the ABL Myristoyl Pocket. This unique mechanism of action allows asciminib to be combined with adenosine triphosphate-competitive tyrosine kinase inhibitors to prevent resistance and enhance efficacy. The phase II ASC4MORE trial investigated the strategy of adding asciminib to imatinib in patients who have not achieved deep molecular response with imatinib. Methods: In ASC4MORE, 84 patients with CML in chronic phase not achieving deep molecular response after ≥ 1 year of imatinib therapy were randomized to asciminib 40 or 60 mg once daily (QD) add-on to imatinib 400 mg QD, continued imatinib 400 mg QD, or switch to nilotinib 300 mg twice daily. Results: More patients in the asciminib 40- and 60-mg QD add-on arms (19.0% and 28.6%, respectively) achieved MR4.5 (BCR::ABL1 ≤ 0.0032% on the International Scale) at week 48 (primary endpoint) than patients in the continued imatinib (0.0%) and switch to nilotinib (4.8%) arms. Fewer patients discontinued asciminib 40- and 60-mg QD add-on treatment (14.3% and 23.8%, respectively) than imatinib (76.2%, including crossover patients) and nilotinib (47.6%). Asciminib add-on was tolerable, with rates of AEs and AEs leading to discontinuation less than those with nilotinib, although higher than those with continued imatinib (as expected in these patients who had already been tolerating imatinib for ≥ 1 year). No new or worsening safety signals were observed with asciminib add-on vs the known asciminib monotherapy safety profile. Overall, these results support asciminib add-on as a treatment strategy to help patients with CML in chronic phase stay on therapy to safely achieve rapid and deep response, although further investigation is needed before this strategy is incorporated into clinical practice.
In dieser Phase-3-Studie untersuchen Brown et al., ob eine zeitlich begrenzte Kombinationstherapie mit Acalabrutinib und Venetoclax – mit oder ohne Obinutuzumab – bei bisher unbehandelten, fitten Patientinnen und Patienten mit chronischer lymphatischer Leukämie (CLL) wirksamer ist als eine herkömmliche Chemoimmuntherapie. Eingeschlossen wurden 867 Personen ohne TP53-Mutation oder 17p-Deletion, die zufällig einer von drei Behandlungsgruppen zugeteilt wurden: Acalabrutinib–Venetoclax, Acalabrutinib–Venetoclax–Obinutuzumab oder Chemoimmuntherapie mit Fludarabin–Cyclophosphamid–Rituximab bzw. Bendamustin–Rituximab. Nach einer mittleren Nachbeobachtungszeit von knapp 41 Monaten zeigte sich, dass die progressionsfreie Überlebensrate nach drei Jahren in den beiden Acalabrutinib-basierten Gruppen deutlich höher war als unter Chemoimmuntherapie. Besonders ausgeprägt war der Vorteil bei zusätzlicher Gabe von Obinutuzumab. Auch das Gesamtüberleben war in der Acalabrutinib–Venetoclax-Gruppe am höchsten. Neutropenien traten unter der Dreifachkombination am häufigsten auf. Todesfälle im Zusammenhang mit COVID-19 wurden in allen Gruppen beobachtet. Insgesamt belegt die Studie, dass die Kombination aus Acalabrutinib und Venetoclax – mit oder ohne Obinutuzumab – das krankheitsfreie Überleben im Vergleich zur Standardtherapie signifikant verlängert.
The number of primary cutaneous lymphoma patients receiving low-dose radiotherapy is increasing, though controlled clinical trials defining the standard radiation dose for each specific entity have not yet been completed. Radiation oncologists are left with making highly individualized decisions that would be better enriched by additional clinical evidence. In this expert opinion, we aim to provide a clear recommendation to improve the current practice of radiation oncology. In addition, existing literature has been reviewed to develop recommendations for all types of primary cutaneous lymphoma. A prospective trial is urgently needed to identify the factors influencing patient outcomes following different radiation doses.
Bei Patienten mit muskelinvasivem Blasenkrebs, die für eine Cisplatin-Behandlung geeignet sind, ist die Standardtherapie eine neoadjuvante Chemotherapie gefolgt von einer radikalen Zystektomie. Es wird untersucht, ob die zusätzliche perioperative Immuntherapie die Behandlungsergebnisse verbessern kann. In dieser Phase-3-Studie wurden Patienten zufällig in zwei Gruppen eingeteilt. Die erste Gruppe erhielt eine Kombination aus Durvalumab und Gemcitabin-Cisplatin vor der Operation und anschließend Durvalumab als Nachbehandlung. Die zweite Gruppe erhielt nur Gemcitabin-Cisplatin vor der Operation. Die Hauptziele der Studie waren das ereignisfreie Überleben und das Gesamtüberleben. Die Studie umfasste insgesamt 1063 Patienten. Nach zwei Jahren lag das ereignisfreie Überleben in der Durvalumab-Gruppe bei etwa 68%, während es in der Vergleichsgruppe bei etwa 60% lag. Das Gesamtüberleben nach zwei Jahren betrug in der Durvalumab-Gruppe etwa 82% und in der Vergleichsgruppe etwa 75%. Schwere Nebenwirkungen traten in beiden Gruppen ähnlich häufig auf. Die Operation wurde bei den meisten Patienten in beiden Gruppen durchgeführt. Die Kombination aus Durvalumab und neoadjuvanter Chemotherapie führte zu besseren Überlebensraten im Vergleich zur alleinigen neoadjuvanten Chemotherapie.
Background: An accurate method of assessing the response of muscle-invasive bladder cancer (MIBC) to neoadjuvant treatment is needed for selecting candidates for bladder-sparing strategies. Purpose: To evaluate the diagnostic accuracy and reproducibility of neoadjuvant chemotherapy Vesical Imaging Reporting and Data System (nacVI-RADS) scores and posttreatment Vesical Imaging Reporting and Data System (VI-RADS) scores when assessing MIBC response to neoadjuvant immunotherapy with multiparametric MRI (mpMRI). Materials and Methods: A retrospective analysis of MRI scans was conducted in patients enrolled in the PURE-01 study (NCT02736266) from February 2017 to December 2019 who underwent pre- and postimmunotherapy mpMRI before radical cystectomy. Five readers independently reviewed the scans using VI-RADS and nacVI-RADS criteria. Diagnostic accuracy was evaluated for each reader, and the final histopathologic diagnosis served as the reference standard. Interreader agreement was assessed with the percentage of agreement, Conger κ, and Gwet agreement coefficient AC1. Results: A total of 110 patients (median age, 67 years [IQR: 61–74]; 96 male) with 220 MRI scans were included; 80 (73%) patients had pure urothelial carcinoma. A total of 46 of 110 (42%) patients achieved a complete pathologic response. The sensitivity, specificity, and negative predictive value of nacVI-RADS 3 or higher for detecting residual disease (higher than stage ypT0) at radical cystectomy were 67%–84%, 63%–96%, and 63%–75%, respectively; for residual muscle-invasive disease (higher than stage ypT1), these values were 91%–98%, 55%–94%, and 93%–98%, respectively. The accuracy of nacVI-RADS was 72%–81% for stage ypT0 or higher disease and 71%–95% for stage ypT1 or higher disease. The accuracy of VI-RADS 3 or higher was 80%–95% for stage ypT1 or higher disease. The percentage of agreement for nacVI-RADS scores was 82% (κ = 0.62–0.65; AC1 = 0.65). Conclusion: The nacVI-RADS scores showed good accuracy and reproducibility when assessing MIBC response to neoadjuvant immunotherapy. Used with permission of RSNA, from Brembilla G, Basile G, Cosenza M, et al. Neoadjuvant Chemotherapy VI-RADS Scores for Assessing Muscle-invasive Bladder Cancer Response to Neoadjuvant Immunotherapy with Multiparametric MRI. Radiology. 2024;313(3):e233020; permission conveyed through Copyright Clearance Center, Inc.
Ziel: Bacillus Calmette-Guérin (BCG) ist seit langem die Standardbehandlung zur Verhinderung von Rezidiven und einer Progression nach Resektion von nicht muskelinvasivem Hochrisiko-Blasenkrebs (NMIBC). Leider treten Rezidive oder eine Progression trotz BCG-Induktions- und Erhaltungstherapie mit einer signifikanten Prävalenz auf – ein anhaltendes Problem in der urologischen Onkologie. Bemerkenswerte Fortschritte bei der Entwicklung alternativer Therapiemöglichkeiten sind verfügbar und befinden sich in der Pipeline. Diese Übersichtsarbeit soll einen Überblick über die aktuelle Behandlungslandschaft für Patienten mit NMIBC und fehlendem BCG-Ansprechen geben und sowohl bestehende als auch neue Therapien vorstellen, die voraussichtlich in Zukunft breiter verfügbar sein werden. Methoden: Eine Übersichtsarbeit auf der Grundlage von bis Ende 2024 erhobenen Daten. Ergebnisse: Neben der radikalen Zystektomie (RC) sind derzeit mehrere Behandlungsoptionen verfügbar oder befinden sich in vielversprechenden Phasen klinischer Studien. Viele dieser Behandlungsmodalitäten erhielten aufgrund ihres anfänglichen Erfolgs den Status «Fast Track» und «Breakthrough Therapy». Dazu gehören neuartige Chemotherapien, Immuncheckpoint-Inhibitoren, gerätegestützte Therapien und neue intravesikale und systemische Wirkstoffe. Es wurden Kombinationstherapien untersucht, bei denen traditionelle Behandlungsformen mit neueren Ansätzen kombiniert werden.
Hintergrund: Die leptomeningeale Karzinomatose ist ein außergewöhnlich seltenes Metastasenmuster bei Urogenitaltumoren, das in weniger als 0,1% der Fälle beschrieben wird. Wir berichten über 2 Fälle von Patienten mit metastasiertem Urothelkarzinom, die zunächst auf Enfortumab Vedotin (EV) ansprachen, bevor sie leptomeningeale Metastasen entwickelten. Falldarstellung: Fall 1: Bei einem 55-jährigen Mann wurde ein metastasiertes Urothelkarzinom diagnostiziert. Er wurde zunächst mit einer Chemotherapie mit Cisplatin/Gemcitabin behandelt, gefolgt von Pembrolizumab als Zweitlinientherapie, wobei unter beiden Therapien eine Progression eintrat. Es wurde bei ihm mit einer EV-Therapie begonnen und er sprach partiell anhaltend auf sie an. Nach 12 Behandlungszyklen entwickelte er neurologische Symptome, wobei sich in der Bildgebung umfangreiche leptomeningeale Metastasen zeigten. Eine Lumbalpunktion wurde durchgeführt, wobei die Zytologie positiv auf ein metastasierendes Karzinom ausfiel. Fall 2: Bei einem 63-jährigen Mann wurde ein metastasiertes Urothelkarzinom diagnostiziert. Er erhielt 6 Zyklen Chemotherapie mit Platin/Gemcitabin, gefolgt von einer Avelumab-Erhaltungstherapie, woraufhin sich bei ihm radiologisch eine Progression entwickelte. Bei ihm wurde mit einer EV-Therapie begonnen, auf die er radiologisch komplett ansprach. Nach 13 Behandlungszyklen entwickelte er neurologische Symptome und in der Bildgebung zeigte sich eine ausgedehnte leptomeningeale Erkrankung. Die Zytologie bestätigte ein metastasiertes Urothelkarzinom. Schlussfolgerung: Dieses ungewöhnliche Ausbreitungsmuster, das bei 2 Patienten beobachtet wurde, die kurz hintereinander mit EV behandelt wurden, stellt ein potenziell signifikantes und neues Progressionsmuster innerhalb dieser Population dar.
Background: Locally advanced cervical cancer is treated with chemoradiotherapy (standard of care), but many patients still relapse and die from metastatic disease. We investigated chemoradiotherapy with or without induction chemotherapy to determine whether induction chemotherapy improves both progression-free survival and overall survival. Methods: The INTERLACE trial was a multicentre, randomised phase 3 trial done at 32 medical centres in Brazil, India, Italy, Mexico, and the UK. Adults (aged ≥18 years) with locally advanced cervical cancer (FIGO 2008 stage IB1 disease with nodal involvement, or stage IB2, IIA, IIB, IIIB, or IVA disease) were randomly assigned (1:1), by minimisation, using a central electronic system, to standard cisplatin-based chemoradiotherapy (once-a-week intravenous cisplatin 40 mg/m2 for 5 weeks with 45·0-50·4 Gy external beam radiotherapy delivered in 20-28 fractions plus brachytherapy to achieve a minimum total 2 Gy equivalent dose of 78-86 Gy) alone or induction chemotherapy (once-a-week intravenous carboplatin area under the receiver operator curve 2 and paclitaxel 80 mg/m2 for 6 weeks) followed by standard cisplatin-based chemoradiotherapy. Stratification factors were recruiting site, stage, nodal status, three-dimensional conformal radiotherapy or intensity modulated radiotherapy, age, tumour size, and histology (squamous vs non-squamous). Primary endpoints were progression-free survival and overall survival within the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT01566240, and EUDRACT, 2011-001300-35. Findings: Between Nov 8, 2012, and Nov 17, 2022, 500 eligible patients were enrolled and randomly assigned to the chemoradiotherapy alone group (n=250) or the induction chemotherapy with chemoradiotherapy group. Of 500 patients, 354 (70%) had stage IIB disease and 56 (11%) stage IIIB disease. Pelvic lymph nodes were positive in 215 (43%) patients. 230 (92%) patients who received induction chemotherapy had at least five cycles. Median interval between induction chemotherapy and chemoradiotherapy was 7 days. Four or more cycles of cisplatin were given to 212 (85%) participants in the induction chemotherapy with chemoradiotherapy group and to 224 (90%) of participants in the chemoradiotherapy alone group. 462 (92%) participants received external beam radiotherapy and brachytherapy with a median overall treatment time of 45 days. After a median follow-up of 67 months, 5-year progression-free survival rates were 72% in the induction chemotherapy with chemoradiotherapy group and 64% in the chemoradiotherapy alone group with a hazard ratio (HR) of 0·65 (95% CI 0·46-0·91, p=0·013). 5-year overall survival rates were 80% in the induction chemotherapy with chemoradiotherapy group and 72% in the chemoradiotherapy alone group, with an HR of 0·60 (95% CI 0·40-0·91, p=0·015). Grade 3 or greater adverse events were reported in 147 (59%) of 250 individuals in the induction chemotherapy with chemoradiotherapy group versus 120 (48%) of 250 individuals in the chemoradiotherapy alone group. Interpretation: Short-course induction chemotherapy followed by chemoradiotherapy significantly improves survival of patients with locally advanced cervical cancer.
Introduction: Bladder cancer, with a greater incidence in males than in females, requires frequent cystoscopies. We aimed to evaluate the effect of music played through noise-canceling headphones on male bladder cancer patients during follow-up cystoscopy. Methods: A total of 160 male bladder cancer patients undergoing follow-up flexible cystoscopy were randomly divided into the noise-canceling headphones without music group and the noise-canceling headphones with music group (groups 1 and 2, respectively; n = 80 per group). The patients' clinical characteristics were examined, and objective and subjective measurements were compared before and after cystoscopy. The primary outcomes that were evaluated included the visual analog scale (VAS, 0-10) and the state-trait anxiety inventory (STAI, 20-80). Other outcomes, including vital signs and scores for assessing satisfaction and the willingness to repeat the procedure, were also examined. Results: The characteristics of the patients in groups 1 and 2, and their pre-cystoscopy status, did not differ significantly. Although post-cystoscopy vital signs for the objective parameters and VAS pain scores were similar between the groups, subjective parameters were not. When compared with group 1, post-cystoscopy STAI-state scores were significantly lower in group 2, whereas patients' satisfaction scores and the willingness to repeat the procedure were significantly higher in group 2 (p = 0.002, 0.001, and 0.001, respectively). Additionally, in group 2, STAI-state scores changed significantly after the procedure when compared with before the procedure (p = 0.002).
Background: The potential benefits of robotic-assisted compared with laparoscopic surgery for locally advanced cancer have not been sufficiently proven by prospective studies. One factor is speculated to be the lack of strict surgeon criteria. The aim of this study was to assess outcomes for robotic surgery in patients with locally advanced rectal cancer with strict surgeon experience criteria. Methods: A criterion was set requiring surgeons to have performed more than 40 robotically assisted operations for rectal cancer. Between March 2020 and May 2022, patients with rectal cancer (distance from the anal verge of 12 cm or less, cT2-T4a, cN0-N3, cM0, or cT1-T4a, cN1-N3, cM0) were registered. The primary endpoint was the rate positive circumferential resection margin (CRM) from the pathological specimen. Secondary endpoints were surgical outcomes, pathological results, postoperative complications, and longterm outcomes. Results: Of the 321 registered patients, 303 were analysed, excluding 18 that were ineligible. At diagnosis: stage I (n = 68), stage II (n = 84) and stage III (n = 151). Neoadjuvant therapy was used in 56 patients. There were no conversions to open surgery. The median console time to rectal resection was 170 min, and the median blood loss was 5 ml. Fourteen patients had a positive CRM (4.6%). Grade III-IV postoperative complications were observed in 13 patients (4.3%).
BACKGROUND: Glioblastoma represents a brain tumor with a notoriously poor prognosis. First-line therapy may include adjunctive Tumor Treating Fields (TTFields) which are electric fields that are continuously delivered to the brain through non-invasive arrays. On a different note, CUSP9v3 represents a drug repurposing strategy that includes 9 repurposed drugs plus metronomic temozolomide. Here, the authors examined whether TTFields enhance the antineoplastic activity of CUSP9v3 against this disease. METHODS: The authors performed preclinical testing of a multimodal approach of TTFields and CUSP9v3 in different glioblastoma models. RESULTS: TTFields had predominantly synergistic inhibitory effects on the cell viability of glioblastoma cells and non-directed movement was significantly impaired when combined with CUSP9v3. TTFields plus CUSP9v3 significantly enhanced apoptosis, which was associated with a decreased mitochondrial outer membrane potential (MOMP), enhanced cleavage of effector caspase 3 and reduced expression of Bcl-2 and Mcl-1. Moreover, oxidative phosphorylation and expression of respiratory chain complexes I, III and IV was markedly reduced. CONCLUSION: TTFields strongly enhance the CUSP9v3-mediated anti-glioblastoma activity. TTFields are currently widely used for the treatment of glioblastoma patients and CUSP9v3 was shown to have a favorable safety profile in a phase Ib/IIa trial (NCT02770378) which facilitates transition of this multimodal approach to the clinical setting.
Background: In Western countries, the current standard of care for resectable gastric cancer is perioperative chemotherapy. Preoperative chemoradiotherapy has been considered, but data are limited regarding this treatment as compared with perioperative chemotherapy alone. Methods: We conducted an international, phase 3 trial in which patients with resectable adenocarcinoma of the stomach or gastroesophageal junction were randomly assigned to receive preoperative chemoradiotherapy plus perioperative chemotherapy or perioperative chemotherapy alone (control). In both groups, patients received either epirubicin, cisplatin, and fluorouracil or fluorouracil, leucovorin, oxaliplatin, and docetaxel both before and after surgery; the preoperative-chemoradiotherapy group also received chemoradiotherapy (45 Gy in 25 fractions of radiation, plus fluorouracil infusion). The primary end point was overall survival, and secondary end points included progression-free survival, pathological complete response, toxic effects, and quality of life. Results: A total of 574 patients underwent randomization at 70 sites in Australasia, Canada, and Europe: 286 to the preoperative-chemoradiotherapy group and 288 to the perioperative-chemotherapy group. A higher percentage of patients in the preoperative-chemoradiotherapy group than in the perioperative-chemotherapy group had a pathological complete response (17% vs. 8%) and greater tumor downstaging after resection. At a median follow-up of 67 months, no significant between-group differences in overall survival or progression-free survival were noted. The median overall survival was 46 months with preoperative chemoradiotherapy and 49 months with perioperative chemotherapy (hazard ratio for death, 1.05; 95% confidence interval, 0.83 to 1.31), and the median progression-free survival was 31 months and 32 months, respectively. Treatment-related toxic effects were similar in the two groups.
