scholarly journals Establishment and Initial Experience of Clinical FLASH Radiotherapy in Canine Cancer Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
Elise Konradsson ◽  
Maja L. Arendt ◽  
Kristine Bastholm Jensen ◽  
Betina Børresen ◽  
Anders E. Hansen ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Residual Disease ◽  
Complete Response ◽  
Initial Study ◽  
Treatment Technique ◽  
Specific Patient ◽  
Ion Chamber ◽  
Depth Dose ◽  
Custom Made ◽  
Canine Cancer

FLASH radiotherapy has emerged as a treatment technique with great potential to increase the differential effect between normal tissue toxicity and tumor response compared to conventional radiotherapy. To evaluate the feasibility of FLASH radiotherapy in a relevant clinical setting, we have commenced a feasibility and safety study of FLASH radiotherapy in canine cancer patients with spontaneous superficial solid tumors or microscopic residual disease, using the electron beam of our modified clinical linear accelerator. The setup for FLASH radiotherapy was established using a short electron applicator with a nominal source-to-surface distance of 70 cm and custom-made Cerrobend blocks for collimation. The beam was characterized by measuring dose profiles and depth dose curves for various field sizes. Ten canine cancer patients were included in this initial study; seven patients with nine solid superficial tumors and three patients with microscopic disease. The administered dose ranged from 15 to 35 Gy. To ensure correct delivery of the prescribed dose, film measurements were performed prior to and during treatment, and a Farmer-type ion-chamber was used for monitoring. Treatments were found to be feasible, with partial response, complete response or stable disease recorded in 11/13 irradiated tumors. Adverse events observed at follow-up ranging from 3-6 months were mild and consisted of local alopecia, leukotricia, dry desquamation, mild erythema or swelling. One patient receiving a 35 Gy dose to the nasal planum, had a grade 3 skin adverse event. Dosimetric procedures, safety and an efficient clincal workflow for FLASH radiotherapy was established. The experience from this initial study will be used as a basis for a veterinary phase I/II clinical trial with more specific patient inclusion selection, and subsequently for human trials.

scholarly journals Differential Gene -Based Predictors of Neoadjuvant Chemotherapy Efficacy in Breast Cancer

2021 ◽  
Author(s):  
Mei Lu ◽  
JieYa Zou ◽  
Rong Guo ◽  
XiaoJuan Yang ◽  
Ji Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Prediction Model ◽  
Cancer Patients ◽  
Residual Disease ◽  
Area Under The Curve ◽  
Complete Response ◽  
Rna Seq ◽  
Breast Cancer Patients ◽  
Expression Levels

Abstract Background and objectiveChemotherapy is the most common treatment in breast cancer , and neoadjuvant chemotherapy (NAC) is wildly used because of it’s efficiency and safety. To identify significantly differentially expressed genes and select the most suitable breast cancer patients for neoadjuvant chemotherapy (NAC) before treatment. MethodsWe collected a total of 60 breast cancer patient samples before and after NAC. All the samples were subjected to high-throughput RNA sequencing (RNA-seq). Then , we identified AHNAK, CIDEA, ADIPOQ, and AKAP12 as candidate genes related to tumour chemotherapeutic resistance. Next, we analysed the expression levels of AHNAK, CIDEA, ADIPOQ, and AKAP12 by logistic regression and based on the result, we constructed a predictive model visualized by a nomogram. ResultsThe RNA-seq results show that AHNAK, CIDEA, ADIPOQ and AKAP12 are upregulated in residual disease after NAC (P<0.05), and compared with the pathological complete response (pCR) group, the non-pCR group presented high AHNAK, CIDEA, ADIPOQ and AKAP12 expression levels (P<0.05). Logistic analysis showed that high AHNAK, CIDEA, ADIPOQ and AKAP12 expression levels significantly reduced the pCR rate of NAC for breast cancer (P<0.05). In addition, our prediction model , which included AHNAK, CIDEA, ADIPOQ and AKAP12 , showed a good fitting effect with the H1 test (χ2=6.3967, P=0.4945) and the receiver operating characteristic (ROC) curve (area under the curve (AUC) 0.8249, 95% CI 0.722–0.9271). ConclusionHigh expression of AHNAK, CIDEA, ADIPOQ and AKAP12 indicates poor treatment response in breast cancer patients treated with NAC . The efficacy prediction model based on these results is expected to be a new method to select the optimal population of breast cancer patients for NAC.

scholarly journals Relationship Between Time Interval From Primary Surgery to the Start of Taxane- Plus Platinum-Based Chemotherapy and Clinical Outcome of Patients With Advanced Epithelial Ovarian Cancer: Results of a Multicenter Retrospective Italian Study

2005 ◽  
Vol 23 (4) ◽  
pp. 751-758 ◽  
Author(s):  
Angiolo Gadducci ◽  
Enrico Sartori ◽  
Fabio Landoni ◽  
Paolo Zola ◽  
Tiziano Maggino ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Outcome ◽  
Cancer Patients ◽  
Residual Disease ◽  
Advanced Ovarian Cancer ◽  
Complete Response ◽  
Time Interval ◽  
Primary Surgery ◽  
Second Look ◽  
Platinum Based Chemotherapy

Purpose To assess whether the interval from primary surgery to the start of taxane- plus platinum-based chemotherapy has any impact on the clinical outcome of advanced ovarian cancer patients. Patients and Methods The study was conducted on 313 patients who underwent surgery followed by taxane- plus platinum-based chemotherapy. The median follow-up of survivors was 30.7 months (range, 6 to 109 months). Results The 25%, 50%, and 75% quantiles of intervals from surgery to the start of chemotherapy were 11, 21, and 31 days, respectively. After the sixth cycle, 102 patients achieved a pathologic complete response at second-look surgery and 98 obtained a clinical complete response but were not submitted to second-look surgery. Taking into consideration the best assessed response, a complete (either clinical or pathologic) response was found in 200 patients. Residual disease (≤ 1 v > 1 cm; P < .0001) and ascites (absent v present; P = .003) were independent predictive factors for achieving a complete response, whereas residual disease (P = .001) and stage (IIc to III v IV; P = .04) were independent prognostic variables for survival. Conversely, statistical analyses failed to detect significant differences in complete response rates and survival among patients with an interval from surgery to chemotherapy shorter than 11 days, 12 to 21 days, 22 to 31 days, and longer than 31 days. Conclusion The interval from surgery to the start of taxane- plus platinum-based chemotherapy seems to have neither a predictive value for response to treatment nor a prognostic relevance for survival of advanced ovarian cancer patients.

Combined high-dose carboplatin and cisplatin, and ifosfamide in previously untreated ovarian cancer patients with residual disease.

1990 ◽  
Vol 8 (7) ◽  
pp. 1226-1230 ◽  
Author(s):  
B Lund ◽  
M Hansen ◽  
O P Hansen ◽  
H H Hansen
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Residual Disease ◽  
Pathologic Complete Response ◽  
Residual Tumor ◽  
Complete Response ◽  
Observation Time ◽  
World Health ◽  
High Dose ◽  
Hematologic Toxicity

Carboplatin 200 mg/m2 day 1, cisplatin 50 mg/m2 days 2 and 3, ifosfamide 1,500 mg/m2 days 1 to 3, and mesna 900 mg/m2 days 1 to 3 every 4 weeks for six cycles were given to 37 previously untreated ovarian cancer patients with residual disease after the primary laparotomy. The median observation time was 17+ months (range, 9+ to 24+ months). Of all the patients, 81% had primary residual disease larger than 2 cm. The overall pathologic response rate (pathologic complete response [PCR] plus partial response [PPR]) in 36 assessable patients was 58%, PCR was 42%. Of the PCR patients, 53% had primary residual tumor larger than 5 cm. The substantial hematologic toxicity was manageable, but also the main reason for dose modifications. During treatment, 92% and 100% of the patients developed WBC and platelet nadir values corresponding to World Health Organization (WHO) grades 3 to 4. Dose-limiting encephalopathy, nephro- and neurotoxicity each occurred in 6% of the patients. The high PCR rate warrants further investigations of combined high-dose platinum and ifosfamide.

Selecting a PRO-CTCAE based subset for patient reported symptom monitoring during lung cancer treatment (Preprint)

2020 ◽  
Author(s):  
Evalien Veldhuijzen ◽  
Iris Walraven ◽  
Jose Belderbos
Keyword(s):  
Lung Cancer ◽  
Clinical Practice ◽  
Cancer Patients ◽  
Treatment Modalities ◽  
European Organization ◽  
Specific Patient ◽  
Symptom Monitoring ◽  
Lung Cancer Patients ◽  
Wide Range ◽  
Patient Reported

BACKGROUND The Patient Reported Outcomes Version of the Common Terminology Criteria of Adverse Events (PRO-CTCAE) item library covers a wide range of symptoms relevant for oncology care. To enable implementation of PRO-CTCAE-based symptom monitoring in clinical practice, there is a need to select a subset of items relevant for specific patient populations. OBJECTIVE The aim of this study was to develop a PRO-CTCAE subset relevant for patients with lung cancer. METHODS The PRO-CTCAE-based subset for lung cancer patients was generated using a mixed methods approach based on the European Organization for Research and Treatment of Cancer (EORTC) guidelines for developing questionnaires, consisting of a literature review and semi-structured interviews with both lung cancer patients and health care practitioners (HCPs). Both patients and HCPs were queried on the relevance and impact of all PRO-CTCAE items. Results were summarized and, after a final round of expert review, a selection of clinically relevant items for lung cancer patients was made. RESULTS A heterogeneous group of lung cancer patients (n=25) from different treatment modalities and HCPs (n=22) participated in the study. A final list of eight relevant PRO-CTCAE items was created: decreased appetite, cough, shortness of breath, fatigue, constipation, nausea, sadness, and pain (general). CONCLUSIONS Based on literature and both professional and patient input, a subset of PRO-CTCAE items has been identified for use in lung cancer patients in clinical practice. Future work is needed to confirm the validity and effectiveness of this PRO-CTCAE lung cancer subset internationally, and in the real-world clinical practice setting.

scholarly journals Boosting Immunity against Multiple Myeloma

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1221
Author(s):  
Raquel Lopes ◽  
Bruna Velosa Ferreira ◽  
Joana Caetano ◽  
Filipa Barahona ◽  
Emilie Arnault Carneiro ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Residual Disease ◽  
Proteasome Inhibitors ◽  
Treatment Strategies ◽  
Complete Response ◽  
Drug Conjugates ◽  
Incurable Disease ◽  
Car T ◽  
Patient’S Outcome ◽  
The Impact

Despite the improvement of patient’s outcome obtained by the current use of immunomodulatory drugs, proteasome inhibitors or anti-CD38 monoclonal antibodies, multiple myeloma (MM) remains an incurable disease. More recently, the testing in clinical trials of novel drugs such as anti-BCMA CAR-T cells, antibody–drug conjugates or bispecific antibodies broadened the possibility of improving patients’ survival. However, thus far, these treatment strategies have not been able to steadily eliminate all malignant cells, and the aim has been to induce a long-term complete response with minimal residual disease (MRD)-negative status. In this sense, approaches that target not only myeloma cells but also the surrounding microenvironment are promising strategies to achieve a sustained MRD negativity with prolonged survival. This review provides an overview of current and future strategies used for immunomodulation of MM focusing on the impact on bone marrow (BM) immunome.

scholarly journals Cost-effectiveness of paclitaxel, doxorubicin, cyclophosphamide and trastuzumab versus docetaxel, cisplatin and trastuzumab in new adjuvant therapy of breast cancer in china

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Qiaoping Xu ◽  
Li Yuanyuan ◽  
Zhu Jiejing ◽  
Liu Jian ◽  
Li Qingyu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cost Effectiveness ◽  
Partial Response ◽  
Cancer Patients ◽  
Transition Probabilities ◽  
Complete Response ◽  
Sensitivity Analyses ◽  
Half Cycle ◽  
Breast Cancer Patients ◽  
Grade 3

Abstract Background Breast cancer is the most common cancer among women in China. Amplification of the Human epidermal growth factor receptor type 2 (HER2) gene is present and overexpressed in 18–20% of breast cancers and historically has been associated with inferior disease-related outcomes. There has been increasing interest in de-escalation of therapy for low-risk disease. This study analyzes the cost-effectiveness of Doxorubicin/ Cyclophosphamide/ Paclitaxel/ Trastuzumab (AC-TH) and Docetaxel/Carboplatin/Trastuzumab(TCH) from payer perspective over a 5 year time horizon. Methods A half-cycle corrected Markov model was built to simulate the process of breast cancer events and death occurred in both AC-TH and TCH armed patients. Cost data came from studies based on a Chinese hospital. One-way sensitivity analyses as well as second-order Monte Carlo and probabilistic sensitivity analyses were performed.The transition probabilities and utilities were extracted from published literature, and deterministic sensitivity analyses were conducted. Results We identified 41 breast cancer patients at Hangzhou First People’s Hospital, among whom 15 (60%) had a partial response for AC-TH treatment and 13 (81.25%) had a partial response for TCH treatment.No cardiac toxicity was observed. Hematologic grade 3 or 4 toxicities were observed in 1 of 28 patients.Nonhematologic grade 3 or 4 toxicities with a reverse pattern were observed in 6 of 29 patients. The mean QALY gain per patient compared with TCH was 0.25 with AC-TH, while the incremental costs were $US13,142. The incremental cost-effectiveness ratio (ICER) of AC-TH versus TCH was $US 52,565 per QALY gained. Conclusions This study concluded that TCH neoadjuvant chemotherapy was feasible and active in HER2-overexpressing breast cancer patients in terms of the pathological complete response, complete response, and partial response rates and manageable toxicities.

scholarly journals PD-L1 Expression after Neoadjuvant Chemotherapy in Triple-Negative Breast Cancers Is Associated with Aggressive Residual Disease, Suggesting a Potential for Immunotherapy

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 746
Author(s):  
Beatriz Grandal ◽  
Manon Mangiardi-Veltin ◽  
Enora Laas ◽  
Marick Laé ◽  
Didier Meseure ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Triple Negative ◽  
Residual Disease ◽  
Checkpoint Inhibitors ◽  
Rapid Development ◽  
Complete Response ◽  
Tumor Burden ◽  
Small Subset ◽  
Breast Cancers ◽  
Residual Cancer Burden

The consequences of neoadjuvant chemotherapy (NAC) for PD-L1 activity in triple-negative breast cancers (TNBC) are not well-understood. This is an important issue as PD-LI might act as a biomarker for immune checkpoint inhibitors’ (ICI) efficacy, at a time where ICI are undergoing rapid development and could be beneficial in patients who do not achieve a pathological complete response. We used immunohistochemistry to assess PD-L1 expression in surgical specimens (E1L3N clone, cutoff for positivity: ≥1%) on both tumor (PD-L1-TC) and immune cells (PD-L1-IC) from a cohort of T1-T3NxM0 TNBCs treated with NAC. PD-L1-TC was detected in 17 cases (19.1%) and PD-L1-IC in 14 cases (15.7%). None of the baseline characteristics of the tumor or the patient were associated with PD-L1 positivity, except for pre-NAC stromal TIL levels, which were higher in post-NAC PD-L1-TC-positive than in negative tumors. PD-L1-TC were significantly associated with a higher residual cancer burden (p = 0.035) and aggressive post-NAC tumor characteristics, whereas PD-L1-IC were not. PD-L1 expression was not associated with relapse-free survival (RFS) (PD-L1-TC, p = 0.25, and PD-L1-IC, p = 0.95) or overall survival (OS) (PD-L1-TC, p = 0.48, and PD-L1-IC, p = 0.58), but high Ki67 levels after NAC were strongly associated with a poor prognosis (RFS, p = 0.0014, and OS, p = 0.001). A small subset of TNBC patients displaying PD-L1 expression in the context of an extensive post-NAC tumor burden could benefit from ICI treatment after standard NAC.

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