Locally advanced lung cancer: an optimal setting for vaccines and other immunotherapies.
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ABSTRACT:
SUBMITTER: Iyengar P
PROVIDER: S-EPMC3689291 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:We aimed to determine the optimal pressure of continuous positive airway pressure (CPAP) for radiotherapy (RT) through changes in the dosimetric parameters and lung volume according to pressure. Patients with locally advanced lung cancer, who underwent CPAP during computed tomography (CT) simulation, were included. The air pressure was raised in five steps of 4, 7, 10, 14, and 17 cmH2O and a CT scan was performed at the baseline and at each pressure step, accompanied by contouring and RT planning. Paired t- and Wilcoxon signed rank tests were used to compare the volumetric and dosimetric parameters according to pressure and interpressure. A total of 29 patients were selected, and 158 CT datasets were obtained. The lung volume increased significantly at all pressures (p < 0.01). The Dmean of the lung decreased significantly from 7 cmH2O (p < 0.01), the V5, V10, V15, and V20 of the lung decreased significantly from 7 cmH2O with increasing pressure, and the Dmean and V5 of the heart decreased significantly from 14 cmH2O with increasing pressure. The V50 showed no significant differences at any pressure. We recommend the use of at least 7 cmH2O with 14 cmH2O as the optimal pressure to achieve the effect of heart preservation.
| S-EPMC9454671 | biostudies-literature
Project description:BackgroundThe relationship between time to surgery (TTS) and survival benefit is not sufficiently demonstrated by previous studies in locally advanced gastric cancer (LAGC). This study aims to assess the impact of TTS after neoadjuvant chemotherapy (NACT) on long-term and short-term outcomes in LAGC patients.MethodsData were collected from patients with LAGC who underwent NACT between January 2007 and January 2018 at our institution. Outcomes assessed were long-term survival, pathologic complete response (pCR) rate, and postoperative complications.ResultsThis cohort of 426 patients was divided into five groups by weeks of TTS. Under cox regression, compared to other groups, the 22-28 days and 29-35 days groups revealed a better OS (≤21 vs. 22-28 days: HR 1.54, 95% CI = 0.81-2.93, P = 0.185; 36-42 vs. 22-28 days: HR 2.20, 95% CI = 1.28-3.79, P = 0.004; 43-84 vs. 22-28 days: HR 1.83, 95% CI = 1.09-3.06, P = 0.022) and PFS (≤21 vs. 22-28 days: HR 1.54, 95% CI = 0.81-2.93, P = 0.256; 36-42 vs. 22-28 days: HR 2.20, 95% CI = 1.28-3.79, P = 0.111; 43-84 vs. 22-28 days: HR 1.83, 95% CI = 1.09-3.06, P = 0.047). Further analysis revealed a better prognosis in patients with TTS within 22-35 days (OS: HR 1.78 95% CI = 1.25-2.54, P = 0.001; PFS: HR 1.49, 95% CI = 1.07-2.08, P = 0.017). Postoperative stay was significantly higher in the ≤21 days group, while other parameters revealed no statistical significance (P > 0.05). Restricted cubic spline depicted the nonlinear relationship between TTS and OS/PFS.ConclusionPatients who received surgery within 3-5 weeks experienced the maximal survival benefit without an increase in postoperative complications or lowering the rate of pCR. Further investigations are warranted.
| S-EPMC7773852 | biostudies-literature
Project description:Locally advanced nonsmall cell lung cancer, due to its varying prognosis, is grouped according to TNM stage IIIA, IIIB and IIIC. Developments over the last 3 years have been focused on the integration of immunotherapy into the combination treatment of a locally definitive therapy (surgery or radiotherapy) and chemotherapy. For concurrent chemoradiotherapy, consolidation therapy with durvalumab was established. Adjuvant targeted therapy has again gained increasing interest. In order to adapt treatment to the specific stage subgroup and its prognosis, fluorodeoxyglucose positron emission tomography/computed tomography and pathological evaluation of the mediastinum are important. Tumours should be investigated for immunological features and driver mutations. Regarding toxicity, evaluation of pulmonary and cardiac function, as well as symptoms and quality of life, is of increasing importance. To improve the management and prognosis of this heterogeneous entity, clinical trials and registries should take these factors into account.
| S-EPMC9488500 | biostudies-literature
Project description:Abstract This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To evaluate the effectiveness and safety of therapeutic vaccines for people with advanced non‐small cell lung cancer (non‐irradiatable stage IIIB and stage IV NSCLC) who have either not received treatment, or have received treatment with chemotherapy, or radiotherapy, or both.
| S-EPMC6673723 | biostudies-literature
Project description:Radiation therapy is an essential component of treatment for locally advanced non-small cell lung cancer (NSCLC) but can be technically challenging because of the proximity of lung tumors to nearby critical organs or structures. The most effective strategy for reducing radiation-induced toxicity is to reduce unnecessary exposure of normal tissues by using advanced technology; examples from photon (X-ray) therapy have included three-dimensional conformal radiation therapy versus its predecessor, two-dimensional radiation therapy, and intensity-modulated photon radiation therapy versus its predecessor, three-dimensional conformal therapy. Using particle-beam therapy rather than photons offers the potential for further advantages because of the unique depth-dose characteristics of the particles, which can be exploited to allow still higher dose escalation to tumors with greater sparing of normal tissues, with the ultimate goal of improving local tumor control and survival while preserving quality of life by reducing treatment-related toxicity. However, the costs associated with particle therapy with protons are considerably higher than the current state of the art in photon technology, and evidence of clinical benefit from protons is increasingly being demanded to justify the higher financial burden on the healthcare system. Some such evidence is available from preclinical studies, from retrospective, single-institution clinical series, from analyses of national databases, and from single-arm prospective studies in addition to several ongoing randomized comparative trials. This review summarizes the rationale for and challenges of using proton therapy to treat thoracic cancers, reviews the current clinical experience, and suggests topics for future research.
| S-EPMC7066957 | biostudies-literature
Project description:Protons interact with human tissue differently than do photons and these differences can be exploited in an attempt to improve the care of lung cancer patients. This review examines proton beam therapy (PBT) as a component of a combined modality program for locally advanced lung cancers. It was specifically written for the non-radiation oncologist who desires greater understanding of this newer treatment modality. This review describes and compares photon (X-ray) radiotherapy (XRT) to PBT. The physical differences of these beams are described and the clinical literature is reviewed. Protons can be used to create treatment plans delivering significantly lower doses of radiation to the adjacent organs at risk (lungs, esophagus, and bone marrow) than photons. Clinically, PBT combined with chemotherapy has resulted in low rates of toxicity compared to XRT. Early results suggest a possible improvement in survival. The clinical results of proton therapy in lung cancer patients reveal relatively low rates of toxicity and possible survival benefits. One randomized study is being performed and another is planned to clarify the clinical differences in patient outcome for PBT compared to XRT. Along with the development of better systemic therapy, newer forms of radiotherapy such as PBT should positively impact the care of lung cancer patients. This review provides the reader with the current status of this new technology in treating locally advanced lung cancer.
| S-EPMC4129522 | biostudies-literature
Project description:Recent US Food and Drug Administration approvals of Provenge(®) (sipuleucel-T) as the first cell-based cancer therapeutic factor and ipilimumab (Yervoy(®)/anticytotoxic T-lymphocyte antigen-4) as the first "checkpoint blocker" highlight recent advances in cancer immunotherapy. Positive results of the clinical trials evaluating additional checkpoint blocking agents (blockade of programmed death [PD]-1, and its ligands, PD-1 ligand 1 and 2) and of several types of cancer vaccines suggest that cancer immunotherapy may soon enter the center stage of comprehensive cancer care, supplementing surgery, radiation, and chemotherapy. This review discusses the current status of the clinical evaluation of different classes of therapeutic cancer vaccines and possible avenues for future development, focusing on enhancing the magnitude and quality of cancer-specific immunity by either the functional reprogramming of patients' endogenous dendritic cells or the use of ex vivo-manipulated dendritic cells as autologous cellular transplants. This review further discusses the available strategies aimed at promoting the entry of vaccination-induced T-cells into tumor tissues and prolonging their local antitumor activity. Finally, the recent improvements to the above three modalities for cancer immunotherapy (inducing tumor-specific T-cells, prolonging their persistence and functionality, and enhancing tumor homing of effector T-cells) and rationale for their combined application in order to achieve clinically effective anticancer responses are addressed.
| S-EPMC4918241 | biostudies-literature
Project description:ObjectiveTo study the prognostic value of baseline leukocytosis or neutrophiliain two retrospective cohorts of stage III Non-Small Cell Lung Cancer (NSCLC) patients.Materials and methodsClinical records of consecutive previously untreated NSCLC patients in our Institution between June 2001 and September 2016 for stage III NSCLC were collected. The prognostic value of pretreatment leucocyte disorders was examined, with focus on patterns of relapse and survival. Leukocytosis and neutrophilia were defined as a leukocyte count or a neutrophil count exceeding 10 and 7 G/L, respectively.ResultsWe identified 238 patients, displaying baseline leukocytosis or neutrophilia in 39% and 40% respectively. Most were diagnosed with adenocarcinoma (48%), and stage IIIB NSCLC (58%). 3-year actuarial overall survival (OS) and progression-free survival (PFS) were 35% and 27% respectively. Local relapses were reported in 100 patients (42%), and distant metastases in 132 patients (55%). In multivariate analysis, leukocytosis, neutrophilia, and induction chemotherapy regimen based on carboplatin/paclitaxel were associated with worse OS and PFS (p<0.05). Neutrophilia independently decreased Locoregional Control (LRC) (HR = 2.5, p<0.001) and Distant Metastasis Control (DMC) (HR = 2.1, p<0.001). Neutrophilia was significantly associated with worse brain metastasis control (p = 0.004), mostly in adenocarcinoma patients (p<0.001).ConclusionIn stage III NSCLC patients, treated with concurrent cisplatin-based chemoradiation, baseline leukocytosis and neutrophilia were associated with worse OS, PFS, LRC, and DMC. In addition with previously available markers, this independent cost-effective biomarker could help to stratify stage III NSCLC population with more accuracy.
| S-EPMC6179235 | biostudies-literature
Project description:BackgroundWe have carried out a study to determine the scope for reducing heart doses in photon beam radiotherapy of locally advanced non-small cell lung cancer (LA-NSCLC).Materials and methodsBaseline VMAT plans were created for 20 LA-NSCLC patients following the IDEAL-CRT isotoxic protocol, and were re-optimized after adding an objective limiting heart mean dose (MDHeart). Reductions in MDHeart achievable without breaching limits on target coverage or normal tissue irradiation were determined. The process was repeated for objectives limiting the heart volume receiving ≥ 50 Gy (VHeart-50-Gy) and left atrial wall volume receiving ≥ 63 Gy (VLAwall-63-Gy).ResultsFollowing re-optimization, mean MDHeart, VHeart-50-Gy and VLAwall-63-Gy values fell by 4.8 Gy and 2.2% and 2.4% absolute respectively. On the basis of associations observed between survival and cardiac irradiation in an independent dataset, the purposefully-achieved reduction in MDHeart is expected to lead to the largest improvement in overall survival. It also led to useful knock-on reductions in many measures of cardiac irradiation including VHeart-50-Gy and VLAwall-63-Gy, providing some insurance against survival being more strongly related to these measures than to MDHeart. The predicted hazard ratio (HR) for death corresponding to the purposefully-achieved mean reduction in MDHeart was 0.806, according to which a randomized trial would require 1140 patients to test improved survival with 0.05 significance and 80% power. In patients whose baseline MDHeart values exceeded the median value in a published series, the average MDHeart reduction was particularly large, 8.8 Gy. The corresponding predicted HR is potentially testable in trials recruiting 359 patients enriched for greater MDHeart values.ConclusionsCardiac irradiation in RT of LA-NSCLC can be reduced substantially. Of the measures studied, reduction of MDHeart led to the greatest predicted increase in survival, and to useful knock-on reductions in other cardiac irradiation measures reported to be associated with survival. Potential improvements in survival can be trialled more efficiently in a population enriched for patients with greater baseline MDHeart levels, for whom larger reductions in heart doses can be achieved.
| S-EPMC8176693 | biostudies-literature
Project description:Radiation is the foundation of treatment for locally advanced non-small cell lung cancer (NSCLC), and as such, optimal radiation dose is essential for successful treatment. This article will briefly review biological considerations of radiation dose and their effect in the context of three-dimensional conformal radiation therapy (3D-CRT) including intensity modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT) for NSCLC. It will focus on literature review and discussions regarding radiation dose effect in locally advanced NSCLC including potential severe and lethal toxicities of high dose radiation given with concurrent chemotherapy. Potential new approaches for delivering safe and effective doses by individualizing treatment based on functional imaging are being applied in studies such as the PET boost trial and RTOG1106. The RTOG concept of delivering high dose radiation to the more resistant tumors with the use of isotoxic dose prescription and adaptive planning will also be discussed in detail.
| S-EPMC3968556 | biostudies-literature