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Critical Reviews in Oncology/hematology Oct 2020Surgery and chemoradiotherapy can potentially cure esophageal and gastric cancer patients, although they may impact health-related quality of life (HRQoL). We aim to... (Meta-Analysis)
Meta-Analysis
Surgery and chemoradiotherapy can potentially cure esophageal and gastric cancer patients, although they may impact health-related quality of life (HRQoL). We aim to systemically review and meta-analyze literature to determine the effect of curative treatments on HRQoL in esophageal and gastric cancer.- A systematic search was performed identifying studies assessing HRQoL. Meta-analyses were performed on baseline and subsequent time-points.- From the 6067 articles retrieved, 49 studies were included (61 % low quality). Meta-analyses showed short-term HRQoL differences between esophageal cancer patients receiving definitive chemoradiotherapy (dCRT), neoadjuvant chemo(radio)therapy (nC(R)T), or surgery alone (p < 0.001), with better HRQoL with nC(R)T and surgery compared to dCRT. Over the course of 12 months, no HRQoL difference was identified between treatments in esophageal cancer (p = 0.633). Esophagectomy, but not gastrectomy, resulted in a clinically relevant decline in HRQoL. No long-term HRQoL differences were identified between curative treatments in esophageal and gastric cancer. More high-quality HRQoL studies are warranted.
Topics: Chemoradiotherapy; Esophageal Neoplasms; Esophagectomy; Humans; Quality of Life; Stomach Neoplasms
PubMed: 32818901
DOI: 10.1016/j.critrevonc.2020.103069 -
International Journal of Radiation... Mar 2023The Lyman model is one of the most used radiobiological models for calculation of normal-tissue complication probability (NTCP). Since its introduction in 1985, many...
PURPOSE
The Lyman model is one of the most used radiobiological models for calculation of normal-tissue complication probability (NTCP). Since its introduction in 1985, many authors have published parameter values for the model based on clinical data of different radiotherapeutic situations. This study attempted to collect the entirety of radiobiological parameter sets published to date and provide an overview of the data basis for different variations of the model. Furthermore, it sought to compare the parameter values and calculated NTCPs for selected endpoints with sufficient data available.
METHODS AND MATERIALS
A systematic literature analysis was performed, searching for publications that provided parameters for the different variations of the Lyman model in the Medline database using PubMed. Parameter sets were grouped into 13 toxicity-related endpoint groups. For 3 selected endpoint groups (≤25% reduction of saliva 12 months after irradiation of the parotid, symptomatic pneumonitis after irradiation of the lung, and bleeding of grade 2 or less after irradiation of the rectum), parameter values were compared and differences in calculated NTCP values were analyzed.
RESULTS
A total of 509 parameter sets from 130 publications were identified. Considerable heterogeneities were detected regarding the number of parameters available for different radio-oncological situations. Furthermore, for the 3 selected endpoints, large differences in published parameter values were found. These translated into great variations of calculated NTCPs, with maximum ranges of 35.2% to 93.4% for the saliva endpoint, of 39.4% to 90.4% for the pneumonitis endpoint, and of 5.4% to 99.3% for the rectal bleeding endpoint.
CONCLUSIONS
The detected heterogeneity of the data as well as the large variations of published radiobiological parameters underline the necessity for careful interpretation when using such parameters for NTCP calculations. Appropriate selection of parameters and validation of values are essential when using the Lyman model.
Topics: Humans; Probability; Radiotherapy Planning, Computer-Assisted; Rectum; Radiobiology
PubMed: 36029911
DOI: 10.1016/j.ijrobp.2022.08.039 -
Cancer Treatment Reviews Sep 2021Despite multimodality treatment for curatively-treated gastroesophageal adenocarcinoma (GEA), prognosis remains dismal. The benefit of adding trastuzumab to chemotherapy...
INTRODUCTION
Despite multimodality treatment for curatively-treated gastroesophageal adenocarcinoma (GEA), prognosis remains dismal. The benefit of adding trastuzumab to chemotherapy for advanced Human Epidermal Growth Factor 2 (HER2) positive GEA has been established in the ToGA trial. However, it remains unclear if HER2 inhibition might also be beneficial in the curative setting. Therefore, we conducted a systematic review to investigate the role of HER2 inhibitors for the curative treatment of GEA.
METHODS
A systematic literature search was performed in PubMed, EMBASE, CENTRAL, and clinicaltrials.gov to identify clinical trials investigating HER2 inhibition for the curative treatment of GEA. Study quality was assessed using the GRADE methodology.
RESULTS
From the 1825 studies retrieved, 17 were included (seven published articles; three published conference abstracts; seven ongoing studies). From the published studies, eight studies investigated single-agent HER2 inhibition. Four studies had a nonrandomized design, and two were randomized controlled trials. Two published studies were assessed as high-quality. The addition of single-agent HER2 inhibition to chemo(radio)therapy showed a pathological complete response rate (pCR) of 22.2% (range, 9.6-25%) and dual HER2 inhibition of 34.5% (34-35%). Two-year disease-free survival (DFS) was 51.0% (40-71%) with single-agent and 70.0% (70-70%) with dual HER2 therapy.
DISCUSSION
Dual-agent HER2 inhibition showed promising pCR rates and DFS. Given the limited additional toxicity of the addition of HER2 targeting agents and the potential benefit of dual-targeting, further investigation is required in a phase III randomized clinical trial. Next steps include combining checkpoint inhibitors and HER2 blockade given the suggested synergism, as well as investigating new anti-HER2 agents.
Topics: Antineoplastic Combined Chemotherapy Protocols; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Esophageal Neoplasms; Humans; Protein Kinase Inhibitors; Randomized Controlled Trials as Topic; Receptor, ErbB-2; Stomach Neoplasms; Trastuzumab
PubMed: 34171733
DOI: 10.1016/j.ctrv.2021.102249 -
Biochimica Et Biophysica Acta. Reviews... Aug 2020Chemotherapy (CT), radiotherapy (RT), and chemoradiotherapy (CRT) are able to alter the composition of the tumor immune microenvironment (TIME). Understanding the effect...
BACKGROUND
Chemotherapy (CT), radiotherapy (RT), and chemoradiotherapy (CRT) are able to alter the composition of the tumor immune microenvironment (TIME). Understanding the effect of these modalities on the TIME could aid in the development of improved treatment strategies. Our aim was to systematically review studies investigating the influence of CT, RT or CRT on different TIME markers.
METHODS
The EMBASE (Ovid) and PubMed databases were searched until January 2019 for prospective or retrospective studies investigating the dynamics of the local TIME in cancer patients (pts) treated with CT, RT or CRT, with or without targeted agents. Studies could either compare baseline and follow-up specimens - before and after treatment - or a treated versus an untreated cohort. Studies were included if they used immunohistochemistry and/or flow cytometry to assess the TIME.
RESULTS
In total we included 110 studies (n = 8850 pts), of which n = 89 (n = 6295 pts) compared pre-treatment to post-treatment specimens and n = 25 (n = 2555 pts) a treated versus an untreated cohort (4 studies conducted both comparisons). For several tumor types (among others; breast, cervical, esophageal, ovarian, rectal, lung mesothelioma and pancreatic cancer) remodeling of the TIME was observed, leading to a potentially more immunologically active microenvironment, including one or more of the following: an increase in CD3 or CD8 lymphocytes, a decrease in FOXP3 Tregs and increased PD-L1 expression. Both CT and CRT were able to immunologically alter the TIME.
CONCLUSION
The TIME of several tumor types is significantly altered after conventional therapy creating opportunities for concurrent or sequential immunotherapy.
Topics: Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Biopsy; Chemoradiotherapy, Adjuvant; Clinical Trials as Topic; Flow Cytometry; Humans; Immunohistochemistry; Immunotherapy; Molecular Targeted Therapy; Neoadjuvant Therapy; Neoplasms; Treatment Outcome; Tumor Microenvironment
PubMed: 32540465
DOI: 10.1016/j.bbcan.2020.188386 -
Oral Oncology Dec 2020The incidence of head and neck squamous cell carcinoma (HNSCC) is increasing worldwide, with over three quarters of cases now diagnosed in low and middle-income...
The incidence of head and neck squamous cell carcinoma (HNSCC) is increasing worldwide, with over three quarters of cases now diagnosed in low and middle-income countries (LMICs) with resource-constraints. Loco-regional recurrence remains the predominant pattern of failure mandating adequate local therapy for acceptable loco-regional control and survival. There is high-quality evidence that intensification of treatment by either by adding concurrent chemotherapy or by altering radiotherapy (RT) fractionation improves outcomes in the curative-intent management of loco-regionally advanced HNSCC. Even conservative estimates indicate that >50% of patients in LMIC are unlikely to get access to timely RT, which will only get compounded with the coronavirus disease (COVID)-19 pandemic. The radiation oncology community has been systematically testing altered fractionation schedules in several solid cancers (breast, lung, and head-neck), given the cost-effectiveness, convenience, and compliance to short-course RT regimens. Radiobiological modelling suggests that standard fractionation of 6-7 weeks in HNSCC can be compressed safely into a 4-week schedule to counter accelerated repopulation by increasing the dose per fraction and delivering 5 fractions per week which is currently being tested in the ongoing multicentric trial of hypo- vs normo-fractionated accelerated RT (HYPNO study). Herein, we discuss the radiobiological basis of curative-intent hypofractionated-accelerated RT schedule delivering 55 Gy in 20 fractions over 4 weeks in HNSCC followed by critical appraisal of the published literature on such regimens with concurrent systemic therapy and its inherent resource-sparing potential applicable across large parts of the world particularly in the context of the ongoing COVID-19 pandemic.
Topics: Clinical Trials, Phase III as Topic; Humans; Models, Biological; Radiation Dose Hypofractionation; Squamous Cell Carcinoma of Head and Neck; Time Factors; Treatment Outcome
PubMed: 33091846
DOI: 10.1016/j.oraloncology.2020.105045