Colorectal Pulmonary Metastases: Pulmonary Metastasectomy Versus Stereotactic Ablative Radiotherapy
Ontology highlight
ABSTRACT:
DISEASE(S): Neoplasm Metastasis,Lung Metastases,Neoplasms, Second Primary,Colorectal Neoplasms,Colorectal Cancer Metastatic
PROVIDER: 14547 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
Similar Datasets
Project description: Not available
| S-EPMC6560524 | biostudies-literature
Project description:BACKGROUND:We compared the treatment outcomes of stereotactic body radiotherapy (SBRT) and metastasectomy in patients with pulmonary metastases. METHODS:Twenty-one patients received SBRT (total radiation doses 60 Gy in 3 fractions or 48 Gy in 4 fractions) and 30 underwent metastasectomy, most (93.3%) with wedge resection. The patients were followed for a median of 13.7 months. The tumor size in the SBRT group was larger than in the metastasectomy group (median 2.5 vs. 1.25 cm; P = 0.015). Patients with synchronous metastases were more likely to be treated with SBRT than with metastasectomy (P = 0.006). RESULTS:There was no significant difference in the local control rates of the treatment groups (P = 0.163). Progression-free survival (PFS) was longer in the metastasectomy than in the SBRT group (P = 0.02), with one and two-year PFS rates of 51.1% and 46% versus 23.8% and 11.9%, respectively. The one and two-year overall survival (OS) rates were 95% and 81.8% in the metastasectomy group and 79.5% and 68.2%, in the SBRT group, respectively. In multivariate analysis, synchronous metastasis was related to poor PFS, and tumor size was the most significant factor affecting OS. There were no significant differences in PFS and OS between treatment groups after dividing patients according to the presence or absence of synchronous metastases. CONCLUSIONS:SBRT is considered a suitable local modality against pulmonary metastases; however, patients with synchronous metastases are only likely to obtain a small benefit from local treatment with either SBRT or surgery.
| S-EPMC6275814 | biostudies-literature
Project description:To study whether or not total mediastinal lymph node dissection in conjunction with pulmonary metastasectomy from colorectal cancer is associated with improved survival compared to pulmonary metastasectomy only.
| 2241319 | ecrin-mdr-crc
Project description:Rationale:
SABR (Stereotactic ablative radiotherapy) is one of the standard treatment options besides surgical resection for limited lung metastases (oligometastases) from colorectal cancer. High efficacy in terms of local control of metastatic lesions treated has been shown. Nevertheless, the precise effect of SABR upon progression-free- and overall survival in these patients is unknown. To further evaluate and develop local treatment options in metastatic disease, more information is necessary regarding the impact upon - and the pattern of - disease progression of local treatment options such as SABR.
Objective:
To determine the effect upon progression free survival and upon tumorload relative to baseline, both at one year after randomisation of immediate SABR versus delayed SABR (a scan-and-personalise policy). Secondarily, patterns of progression, patient-reported symptoms and quality of life will be monitored.
| 2187734 | ecrin-mdr-crc
Project description:Although it is usually described as an immunosuppressive modality and not thought of as immunotherapy, there are new preclinical evidences suggesting that high-dose ionizing irradiation (IR) results in direct tumour cell death and augments tumour-specific immunity, which enhances tumour control both locally and distantly. Importantly, IR effects exceed the classical cytocidal properties by also causing phenotypic changes in the fraction of surviving cells, markedly enhancing their susceptibility to T cell-mediated elimination. However, not all IR-induced modifications of the tumour and its microenvironment favor immune rejection. The tumour microenvironment is populated by various types of inhibitory immune cells including Tregs, alternatively activated macrophages, and myeloid-derived suppression cells (MDSCs), which suppress T cell activation and promote tumour outgrowth. Chiang et al. showed the accumulation of pro-tumourigenic M2 macrophages in areas of hypoxia present in irradiated tumours. IR then may also induced responses that are inadequate to maintain antitumuor immunity.
Close interaction between IR, T cells, and the PD-L1/PD-1 axis exsit and provide a basis for the rational design of combination therapy with immune modulators and radiotherapy. Deng et al. demonstrate that PD-L1 was upregulated in the tumour microenvironment after IR. Moreover, administration of anti-PD-L1 enhanced the efficacy of IR through a cytotoxic T cell-dependent mechanism. Concomitant with IR-mediated tumour regression, IR and anti-PD-L1 synergistically reduced the local accumulation of tumour-infiltrating MDSCs, which suppress T cells and alter the tumour immune microenvironment. Finally, activation of cytotoxic T cells with combination therapy mediated the reduction of MDSCs in tumours through the cytotoxic actions of TNF. Sagiv-Barfi et al, also demonstrated in 5 patients receiving atezolizumab and radiation therapy, at least stabilization of systemic progression in all patients and a RECIST partial response at systemic sites in 1 patient. Transient, grade 1-2 inflammatory adverse events (fevers, flu-like symptoms) occurred with no serious immune-related toxicities. Abscopal out-field effects of irradiation has also been described in addition to a reduction in circulating MDSCs in a melanoma patient treated with the anti CTLA-4 ipilimumab and radiotherapy.
Lastly, recent evidence demonstrates that loco-regional curative treatment with stereotactic ablative radiotherapy (SABR) is a good alternative as compared with conventional 3D RT for patients with solid tumour, with durable remissions and a low toxicity profile. Many non-randomised studies have shown that SBRT for oligometastases is safe and effective, with local control rates of about 80%. Importantly, these studies also suggest that the natural history of the disease is changing, with 2-5 year progression-free survival of about 20%. For colorectal, non-small cell, and renal cell cancers, 1-year metastasis control rates ranged from 67 to 91%. Moreover, abscopal reponses in the setting of immune checkpoints inhibitors and radiotherapy combinations have been made in the setting of metastatic disease event in patients with extensive tumor burden. The goal of SABR is to deliver appropriate metastasis directed radiotherapy while minimizing exposure of surrounding normal tissues. Interestingly, the dose and fractionation employed modulate RT ability to synergize with immunotherapy. Vanpouille-Box et al, showed that immune response genes were differentially expressed in irradiated tumours by 8Gyx3 but not 20Gyx1. This highlight the interest of hypofractionated SABR acting as a "in situ tumour vaccine".
As hypofractionated SABR may, in addition to its good local control, increase the effectiveness of anti PD-L1, investigators aimed to investigate the efficacy and the tolerability of the combination of anti-PD-L1 antibody with SABR.
| 2232071 | ecrin-mdr-crc
Project description:BackgroundFor the local management of pulmonary malignancies, surgical resection and stereotactic body radiation therapy (SBRT) are mutually exclusive treatments. This study aims to assess the effectiveness of SBRT on reducing tumor viability at a histologic level in the context of pulmonary metastases.MethodsThis protocol describes an open-label unblinded single-arm prospective Phase 2 trial to determine the effects of dual treatment of pulmonary metastasis amenable to curative resection using neoadjuvant SBRT followed by surgical resection, the Post SBRT Pulmonary Metastasectomy (PSPM) trial. Sample size require 39 patients, with an anticipated study duration of 30-36 months. Following completion of SBRT, eligible patients will be assessed at the 4-6-week mark by the treating radiation oncologist and thoracic surgeon with a post-treatment computed tomography (CT) of the chest. Patients with no disease progression will undergo scheduled surgical resection of all metastatic tumors at 8-12 weeks post SBRT. Patients will then be evaluated postoperatively at 30 days, and every 6 months for a total of 36 months with surveillance CT scans. Patients will also undergo sequential serologic evaluation of circulating tumor DNA (ctDNA) levels throughout their respective treatment pathway. The primary outcome of this study is the rate of complete pathologic response (pCR) following SBRT, assess using the International Association for the Study of Lung Cancer (IASLC) multidisciplinary recommendations for pathologic assessment of lung cancer resection specimens after neoadjuvant therapy. Secondary outcomes include overall survival (OS), disease free survival (DFS), local recurrence rates, cancer histology effects on pCR and treatment related complications, and treatment effect on ctDNA levels. Primary and secondary outcomes will be analyzed using Fisher's Exact test and Student's t-test based on data type. Cox-proportional hazard ratios will be used to evaluate OS and DFS, using the log rank test.DiscussionIn evaluating the effect of SBRT on pulmonary metastasis at a histologic level, this trial may increase the use of this modality in selected patients who would otherwise only undergo surgery for disease that has already metastasized. Also, the trial provides secondary benefits of evaluating the abscopal effects of radiation on pulmonary metastatic disease, and serves as a platform for more comprehensive large-scale research in this field.Trial registrationClinicalTrials.gov identifier: NCT04160143 (HiREB: 7925).
| S-EPMC9091013 | biostudies-literature
Project description:Metastasectomy is the most frequent surgical resection undertaken by thoracic surgeons, being the lung the second common site of metastases. The present oncological criteria for pulmonary metastasectomy are: (I) the primary cancer need to be controlled or controllable; (II) no extrathoracic metastasis-that is not controlled or controllable-exists; (III) all of the tumor must be resectable, with adequate pulmonary reserve; (IV) there are no alternative medical treatment options with lower morbidity. General favourable prognostic features in patients with pulmonary metastases are: (I) one or few metastases; (II) long disease free interval; (III) normal CEA levels in colorectal cancers. Negative predictive features in patients candidate to pulmonary metastasectomies are: (I) active primary cancer; (II) extrathoracic metastases; (III) inability to obtain surgical radicality; (IV) mediastinal lymphatic spread. The lack of controlled trials and studies limited by short follow-up and small cohorts did not allow to overcome some skepticism; moreover, the heterogeneity of these patients in terms of demographic, biologic and histologic characteristics represents a clear limit even in the largest series. On the basis of present knowledge, without results coming from on-going randomized trials, radical resection, histology, and disease free interval seem to be independent prognostic factors identifying a cohort of patients maximally benefitting from lung metastasectomy.
| S-EPMC5653506 | biostudies-other
Project description:Lymph node (LN) removal during pulmonary metastasectomy is a prerequisite to achieve complete resection or at least collect prognostic information, but is not yet generally accepted. On average, the rate of unexpected lymph node involvement (LNI) is less than 10% in sarcoma, 20% in colorectal cancer (CRC) and 30% in renal cell carcinoma (RCC) when radical LN dissection is performed. LNI is a negative prognostic factor and presence of preoperative mediastinal disease usually leads to exclusion of the patient from metastasis surgery. Nonetheless, some authors found excellent prognoses even with mediastinal LNI in colorectal and RCC metastases when radical LN dissection was performed (median survival of 37 and 36 months, respectively). Multiple metastases, central location of the lesion followed by anatomical resections are associated with a higher LNI rate. The real prognostic influence of systematic LN dissection remains unclear. Two positive effects were described after radical lymphadenectomy: a trend for improved survival in RCC patients and a reduction of mediastinal recurrences from 23% to 0% in CRC patients. Unfortunately, there is a great number of studies that do not demonstrate any positive effect of lymphadenectomy during pulmonary metastasectomy except a pseudo stage migration effect. Future studies should not only focus on survival, but also on local and LN recurrence.
| S-EPMC8107571 | biostudies-literature
Project description:Background The abscopal effect was described as early as the 1950s, when untreated tumors demonstrated a response after radiation therapy was delivered to an untreated, distant site. The mechanisms underlying this global response to otherwise localized therapy remain unknown, though there is increasing evidence that increased antigen expression following ablative radiotherapy may play a role. Case presentation We report a case of a 69-year-old African American woman with a history of metastatic typical pulmonary carcinoid with multiple lung nodules who had a significant decrease in size of an untreated left upper lobe nodule after stereotactic body radiation therapy to an oligoprogressive left lower lobe lesion. Conclusions To our knowledge, this report describes the first case of an abscopal effect in a typical pulmonary carcinoid. Further research is needed regarding the mechanisms responsible for this finding and the role of combining radiation therapy and cancer immunotherapy in patients with pulmonary carcinoid tumors.
| S-EPMC7532944 | biostudies-literature
Project description:Stereotactic ablative radiotherapy (SABR) may improve survival in patients with inoperable pulmonary oligometastases. However, the impact of pulmonary oligometastatic status after systemic therapy on SABR outcomes remains unclear. Hence, we investigated the outcomes of SABR in 45 patients with 77 lung tumors and the prognostic value of pulmonary oligoprogression. Eligibility criteria were pulmonary oligometastases (defined as ≤5 metastatic lung tumors), controlled extrapulmonary disease (EPD) after front-line systemic therapy, SABR as primary local treatment for inoperable pulmonary metastases, and consecutive imaging follow-up. Oligometastatic lung tumor was classified into controlled or oligoprogressive status. Overall survival (OS), in-field progression-free survival (IFPFS), out-field progression-free survival (OFPFS), and prognostic variables were evaluated. With 21.8 months median follow-up, the median OS, IFPFS, and OFPFS were 28.3, not reached, and 6.5 months, respectively. Two-year OS, IFPFS, and OFPFS rates were 56.0%, 74.2%, and 17.3%, respectively. Oligoprogressive status (p = 0.003), disease-free interval < 24 months (p = 0.041), and biologically effective dose (BED10) < 100 Gy (p = 0.006) were independently associated with inferior OS. BED10 ≥ 100 Gy (p = 0.029) was independently correlated with longer IFPFS. Oligoprogressive status (p = 0.017) and EPD (p = 0.019) were significantly associated with inferior OFPFS. Grade ≥ 2 radiation pneumonitis occurred in four (8.9%) patients. Conclusively, SABR with BED10 ≥ 100 Gy could provide substantial in-field tumor control and longer OS for systemic therapy respondents with inoperable pulmonary oligometastases. Oligoprogressive lung tumors exhibited a higher risk of out-field treatment failure and shorter OS. Hence, systemic therapy should be tailored for patients with oligoprogression to reduce the risk of out-field treatment failure. However, in the absence of effective systemic therapy, SABR is a reasonable alternative to reduce resistant tumor burden.
| S-EPMC10177978 | biostudies-literature