Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma.

Glioblastoma is the most common primary malignant brain tumor in adults and is associated with poor survival. The Ivy Foundation Early Phase Clinical Trials Consortium conducted a randomized, multi-institution clinical trial to evaluate immune responses and survival following neoadjuvant and/or adjuvant therapy with pembrolizumab in 35 patients with recurrent, surgically resectable glioblastoma. Patients who were randomized to receive neoadjuvant pembrolizumab, with continued adjuvant therapy following surgery, had significantly extended overall survival compared to patients that were randomized to receive adjuvant, post-surgical programmed cell death protein 1 (PD-1) blockade alone. Neoadjuvant PD-1 blockade was associated with upregulation of T cell- and interferon-γ-related gene expression, but downregulation of cell-cycle-related gene expression within the tumor, which was not seen in patients that received adjuvant therapy alone. Focal induction of programmed death-ligand 1 in the tumor microenvironment, enhanced clonal expansion of T cells, decreased PD-1 expression on peripheral blood T cells and a decreasing monocytic population was observed more frequently in the neoadjuvant group than in patients treated only in the adjuvant setting. These findings suggest that the neoadjuvant administration of PD-1 blockade enhances both the local and systemic antitumor immune response and may represent a more efficacious approach to the treatment of this uniformly lethal brain tumor

Neoadjuvant chemotherapy and trastuzumab versus neoadjuvant chemotherapy followed by post-operative trastuzumab for patients with HER2-positive breast cancer

Neoadjuvant chemotherapy plus trastuzumab (NCT) increases the rate of pathological complete response (pCR) and event-free survival (EFS) compared to neoadjuvant chemotherapy (NC) alone in women with HER2 positive breast cancer (BC). pCR in this setting is associated with improved EFS. Whether NCT preferentially improves EFS in comparison to NC followed by adjuvant trastuzumab initiated postoperatively (NCAT) has not been addressed. Using clinical data from women with HER2 positive BC treated at 7 European institutions between 2007 and 2010 we sought to investigate the impact on breast cancer outcomes of concomitant (NCT) versus sequential (NCAT) treatment in HER2 positive early BC. The unadjusted hazard ratio (HR) for event free survival with NCT compared with NCAT was 0.63 (95% CI 0.37–1.08; p = 0.091). Multivariable analysis revealed that treatment group, tumour size and ER status were significantly associated with EFS from diagnosis. In the whole group NCT was associated with a reduced risk of an event relative to NCAT, an effect that was confined to ER negative (HR: 0.25; 95% CI, 0.10–0.62; p = 0.003) as opposed to ER positive tumours (HR: 1.07; 95% CI, 0.46–2.52; p = 0.869). HER2 positive/ER negative BC treated with NC gain greatest survival benefit when trastuzumab is administered in both the neoadjuvant and adjuvant period rather than in the adjuvant period alone. These data support the early introduction of targeted combination therapy in HER2 positive/ER negative BC

Neoadjuvant therapy for breast cancer

Objective: To evaluate the frequency of neoadjuvant therapy (NT) in women with stage I–III breast cancer in Italy and whether it is influenced by biological characteristics, screening history, and geographic area. Methods: Data from the High Resolution Study conducted in 7 Italian cancer registries were used; they are a representative sample of incident cancers in the study period (2009–2013). Included were 3546 women aged <85 years (groups <50, 50–69, 70–64, and 75+) with stage I–III breast cancer at diagnosis who underwent surgery. Women were classified as receiving NT if they received chemotherapy, target therapy, and/or hormone therapy before the first surgical treatment. Logistic models were built to test the association with biological and contextual variables. Results: Only 8.2% of women (290 cases) underwent NT; the treatment decreases with increasing age (14.5% in age <50 and 2.2% in age 75+), is more frequent in women with negative receptors (14.8%), HER2-positive (15.7%), and triple-negative (15.6%). The multivariable analysis showed the probability of receiving NT is higher in stage III (odds ratio [OR] 3.83; 95% confidence interval [CI] 2.83–5.18), luminal B (OR 1.87; 95% CI 1.27–2.76), triple-negatives (OR 1.88; 95% CI 1.15–3.08), and in symptomatic cancers (OR 1.98; 95% CI 1.13–3.48). Use of NT varied among geographic areas: Reggio Emilia had the highest rates (OR 2.29; 95% CI 1.37–3.82) while Palermo had the lowest (OR 0.41; 95% CI 0.24–0.68). Conclusions: The use of NT in Italy is limited and variable. There are no signs of greater use in hospitals with more advanced care

Breast cancer: Monitoring response to neoadjuvant chemotherapy using Tc-99m sestamibi scintimammography

Background: Aim of the study was to assess the value of scintimammography using Tc-99m sestamibi in the evaluation of tumor response to neoadjuvant chemotherapy. Material and Methods: Results were calculated for 9 patients undergoing neoadjuvant chemotherapy. Scintimammography using 740 MBq Tc-99m sestamibi was performed before, during and after chemotherapy, and sestamibi uptake was scored visually and semiquantitatively to evaluate tumor response. Results: In the case of complete response (n = 3) sestamibi uptake decreased 8 days after beginning neoadjuvant chemotherapy and normalized in the following course. Focal uptake decreased more slowly in patients with partial response (n = 3), who showed clear, persisting tracer accumulation after therapy. The patients without response (n = 3) showed a persisting high tumor activity even after chemotherapy was completed. Conclusions: The preliminary data suggest that in contrast to other imaging modalities scintimammography appears to yield early information regarding tumor response to neoadjuvant chemotherapy

Neoadjuvant endocrine therapy for luminal breast cancer treatment: a first-choice alternative in times of crisis such as the COVID-19 pandemic

The epidemiological emergency caused by CoV-2 (COVID-19) has changed priorities in breast cancer management. In those places where the pandemic has had the greatest effect, it is of paramount importance for most patients to be at home, reducing or postponing their attendance at clinics, as well as avoiding surgeries. In this scenario, neoadjuvant endocrine treatment could be an appropriate alternative treatment for hormone receptor positive breast cancer (luminal-like tumours) in order to minimise hospital admissions and to delay elective surgeries. Accordingly, we present a simple protocol that can be applied to most cases of luminal-like breast cancer and is appropriate for the majority of secondary or tertiary medical centres, or even primary car

Current Oncological Treatment of Patients with Pancreatic Cancer in Germany: Results from a National Survey on behalf of the Arbeitsgemeinschaft Internistische Onkologie and the Chirurgische Arbeitsgemeinschaft Onkologie of the Germany Cancer Society

Background: No data have previously been available regarding the current treatment of patients with pancreatic cancer (PC) in German hospitals and medical practices. Methods: Between February 2007 and March 2008 we conducted a national survey {[}on behalf of the Arbeitsgemeinschaft Internistische Onkologie (AIO) and the Chirurgische Arbeitsgemeinschaft Onkologie (CAO)] regarding the current surgical and oncological treatment of PC in Germany. Standardized questionnaires were sent via mailing lists to members of the AIO and CAO (n = 1,130). The data were analyzed using SPSS software (version 16.0). Pre-defined subgroup analysis was performed by grouping the results of each question with regard to the professional site of the responding physician and to the number of patients treated in their institution by year. Results: 181 (16%) of the oncological questionnaires were sent back. For 61% of the participating centers, a histological confirmation of PC diagnosis is obligatory. 21% of physicians offer neoadjuvant therapy to patients with potentially resectable PC. In the adjuvant treatment after curative-intent surgery, gemcitabine (Gem) is regarded as standard of care by 71% after R0 resection and 62% after R1 resection. For patients with locally advanced PC, 52% of the participating centers recommend systemic chemotherapy, 17% prefer combined primary chemoradiotherapy. Most centers (59%) base their decision of combination regimens for metastatic disease on the performance status of their patients. In patients with a good status, 28% apply single-agent Gem, 3% use Gem + capecitabine, 12% Gem + erlotinib, 16% Gem + oxaliplatin, and 8% Gem + cisplatin. Only 28% of the survey doctors offer second-line treatment to the majority of their patients with advanced PC. Conclusion: Not every PC patient in Germany is treated according to the present S3 guidelines. Diagnosis and treatment of PC in Germany still need to be improved. Copyright (C) 2009 S. Karger AG, Base

Evaluation of the Systemic and Regional Antibiotic Therapy Effectiveness as Part of Complex Therapy in Patients with Locally Spread Breast Cancer

In recent years, breast cancer is the most common oncologic pathology and the most common cause of disability among women in developed countries.The aim of the study. To improve direct and long-term results of treatment in patients with locally spread forms of breast cancer (LSBC) by accelerated regression of perifocal inflammatory changes using selective intraarterial application of antibiotics; improving patients' quality of life.Materials and methods. The main sample consisted of 109 patients.The control group included 65 (61 %) clinical cases of LSBC who were performed series of courses of intravenous systemic polychemotherapy (SPHT) as neoadjuvant therapy accompanied by systemic intravenous antibiotic therapy. The study group consisted of 42 (39 %) patients who were performed selective intraarterial neoadjuvant polychemotherapy course with simultaneous regional use of antibiotic therapy in the intraarterial administration.Results. The regional administration of antibiotics as a part of the complex neoadjuvant therapy, along with the method of selective intraarterial polychemotherapy, has a positive effect on the linear and chronometric regression of perifocal inflammatory changes around the focus of the primary inoperable LSBC, which positively affects the somatic and psychological patient's state and increases the quality of his life.Conclusions. The complex regional impact on the affected organ has a statistically confirmed better effect with bright holistic features, demonstrating the additive synergism of selective techniques.The selective intraarterial antibiotic therapy does not require additional time and material costs while increasing the efficiency of the method. The versatile advanced approach positively affects the somatic and psychological state of the patient

Chemotherapy-Response Monitoring of Breast Cancer Patients Using Quantitative Ultrasound-Based Intra-Tumour Heterogeneities

© 2017 The Author(s). Anti-cancer therapies including chemotherapy aim to induce tumour cell death. Cell death introduces alterations in cell morphology and tissue micro-structures that cause measurable changes in tissue echogenicity. This study investigated the effectiveness of quantitative ultrasound (QUS) parametric imaging to characterize intra-tumour heterogeneity and monitor the pathological response of breast cancer to chemotherapy in a large cohort of patients (n = 100). Results demonstrated that QUS imaging can non-invasively monitor pathological response and outcome of breast cancer patients to chemotherapy early following treatment initiation. Specifically, QUS biomarkers quantifying spatial heterogeneities in size, concentration and spacing of acoustic scatterers could predict treatment responses of patients with cross-validated accuracies of 82 ± 0.7%, 86 ± 0.7% and 85 ± 0.9% and areas under the receiver operating characteristic (ROC) curve of 0.75 ± 0.1, 0.80 ± 0.1 and 0.89 ± 0.1 at 1, 4 and 8 weeks after the start of treatment, respectively. The patients classified as responders and non-responders using QUS biomarkers demonstrated significantly different survivals, in good agreement with clinical and pathological endpoints. The results form a basis for using early predictive information on survival-linked patient response to facilitate adapting standard anti-cancer treatments on an individual patient basis

Increased lymph node yield in colorectal cancer is not necessarily associated with a greater number of lymph node positive cancers

Peer reviewedPublisher PD

Prospective, open, multi-centre phase I/II trial to assess safety and efficacy of neoadjuvant radiochemotherapy with docetaxel and oxaliplatin in patients with adenocarcinoma of the oesophagogastric junction

Background: This phase I/II-trial assessed the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of neoadjuvant radiochemotherapy (RCT) with docetaxel and oxaliplatin in patients with locally advanced adenocarcinoma of the oesophagogastric junction. Methods: Patients received neoadjuvant radiotherapy (50.4 Gy) together with weekly docetaxel (20 mg/m2 at dose level (DL) 1 and 2, 25 mg/m2 at DL 3) and oxaliplatin (40 mg/m2 at DL 1, 50 mg/m2 at DL 2 and 3) over 5 weeks. The primary endpoint was the DLT and the MTD of the RCT regimen. Secondary endpoints included overall response rate (ORR) and progression-free survival (PFS). Results: A total of 24 patients were included. Four patients were treated at DL 1, 13 patients at DL 2 and 7 patients at DL 3. The MTD of the RCT was considered DL 2 with docetaxel 20 mg/m2 and oxaliplatin 50 mg/m2. Objective response (CR/PR) was observed in 32% (7/22) of patients. Eighteen patients (75%) underwent surgery after RCT. The median PFS for all patients (n = 24) was 6.5 months. The median overall survival for all patients (n = 24) was 16.3 months. Patients treated at DL 2 had a median overall survival of 29.5 months. Conclusion: Neoadjuvant RCT with docetaxel 20 mg/m2 and oxaliplatin 50 mg/m2 was effective and showed a good toxicity profile. Future studies should consider the addition of targeted therapies to current neoadjuvant therapy regimens to further improve the outcome of patients with advanced cancer of the oesophagogastric junction. Trial Registration: NCT0037498