Clinical study on efficacy and safety of autologous gamma/delta T cell transfer therapy after pulmonary metastasectomy of colorectal cancer
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ABSTRACT:
DISEASE(S): Lung Metastasis Of Colorectal Cancer
PROVIDER: 2616356 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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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.
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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.
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Project description:Pulmonary oligo-metastases and oligo-recurrences are terms used to define a set of clinical conditions consisting of limited metastatic malignant disease characterized by an intermediate aggressive behavior compared to diffuse metastatic conditions. If the primary tumor has been controlled and extra-thoracic lesions are excluded, there is a suggestion in the medical literature that removal of such lesions could potentially prolong survival. The lungs are a common metastatic spreading site, especially from epithelial malignancies and sarcomas; pulmonary surgical or interventional metastasectomy have been proposed with curative intent in case of limited tumor load (usually less than 5 lesions). There are many series reporting data about colorectal, renal or breast lung metastasectomy, but the absence of multi centric prospective trials determines a lack of definitive evidence, especially for less common tumors such as metastatic germ cell and prostate cancer. They rarely present in the oligo-metastatic form and their management is often based on personal experience. The aim of our article is to review the latest evidence in the treatment of pulmonary metastatic germ cell and prostate tumors. We cover the full range of treatments: from surgery to ablative radiotherapy and combination of local and systemic therapy. Despite the absence of evidence based guidelines, it emerges that pulmonary metastasectomy should always be considered when general criteria for resection have been met. In germ cell tumors surgery should be mainly reserved for residual disease after chemotherapy, whereas in prostate cancer, pulmonary metastasectomy should be preferred to avoid or delay hormonal deprivation therapy and its side effects.
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Project description:Lung metastases are a common site of spread for many malignant tumours. Pulmonary metastasectomy has been practiced for many years for sarcomas and is now becoming increasingly frequently advocated for patients with many other tumours, especially colorectal cancer. In this article we argue that this procedure is one framed by therapeutic opportunity and not supported by strong evidence. It is potentially harmful and may not be effective. Our argument is based on several important issues: (I) the vagueness of the concept of "oligometastases" and its biological implausibility; (II) the flaws in the often-cited observational evidence, especially selection bias; (III) the lack of any reliable randomised trial evidence of improved survival but evidence of harm; (IV) the failure of strategies to detect metastases earlier to influence overall survival. The introduction of stereotactic radiotherapy and image-guided thermal ablation have made the urge to treat lung metastases stronger but without any good evidence to justify their use. We acknowledge the problems of carrying out randomised trials when there is a clear lack of equipoise in the clinical teams involved but believe that there is an ethical need to do so. Many patients are probably being given false hope of cure or prolonged survival but are at risk of harm from pulmonary metastasectomy or ablation. It is possible that a few patients may benefit but without better evidence we do not know which, if any, do.
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Project description:Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. It is estimated that 50% of all patients with CRC develop metastases, most commonly in the liver and the lung. Lung metastases are seen in approximately 10-15% of all patients with CRC. A large number of these patients with metastatic CRC can only receive palliative treatment due to invasion of other organs and disseminated disease. However, a subset of these patients present with potentially resectable metastases. Pulmonary metastasectomy is considered to be a potentially curative treatment for selected patients with resectable metastatic CRC. Current data suggest that patients that undergo pulmonary metastasectomy have 5-year survival rates of approximately 40%. However, the majority of data published regarding lung metastasectomy is based on small, retrospective case series. Due to this lack of prospective data, it is still unclear which subset of patients will benefit most from curative-intent surgery. Furthermore, there is also controversy regarding which prognostic and genetic factors are related to survival outcomes and whether there is a difference between open and thoracoscopic approaches in terms of overall and disease-free survival. In this review, we aim to summarize the latest data on prognostic factors and survival outcomes after pulmonary metastasectomy in patients with metastatic CRC.
| S-EPMC8107514 | biostudies-literature
Project description:Repeat surgical resection (redo) for pulmonary metastases is a questionable, albeit intriguing topic. We performed an extensive review of the literature, to specifically analyze results of redo pulmonary metastasectomies. We reviewed a total of 3,523 papers. Among these, 2,019 were excluded for redundancy and 1,105 because they were not completely retrievable. Out of 399 eligible papers, 183 had missing information or missing abstract, while 96 lacked data on survival. A total of 120 papers dated from 1991 onwards were finally included. Data regarding mortality, major morbidity, prognostic factors and long-term survivals of the first redo pulmonary metastasectomies were retrieved and analyzed. Homogeneity of data was affected by the lack of guidelines for redo pulmonary metastasectomy and the risks of bias when comparing different studies has to be considered. According to the histology sub-types, redo metastasectomies papers were grouped as: colorectal (n=42), sarcomas (n=36), others (n=20) and all histologies (n=22); the total number of patients was 3,015. Data about chemotherapy were reported in half of the papers, whereas targeted or immunotherapy in 9. None of these associated therapies, except chemotherapy in two records, did significantly modify outcomes. Disease-free interval before the redo procedure was the prevailing prognostic factor and nearly all papers showed a significant correlation between patients' comorbidities and prognosis. No perioperative mortality was reported, while perioperative major morbidity was overall quite low. Where available, overall survival after the first redo metastasectomy ranged from 10 to 72 months, with a 5-years survival of approximately 50%. The site of first recurrence after the redo procedure was mainly lung. Despite the data retrievable from literature are heterogeneous and confounding, we can state that redo lung metastasectomy is worthwhile when the lesions are resectable and the perioperative risk is low. At present, there are no "non-surgical" therapeutic options to replace redo pulmonary metastasectomies.
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Project description:Single-incision thoracoscopic surgery has increasingly attracted public interest and been applied in numerous thoracic procedures. However, single-incision thoracoscopic surgery is associated with requiring subsequent procedures, such as intercostal neuralgia. Herein, we extend the single-port technique of pulmonary metastasectomy through a single subxiphoid approach, and report the first two cases of this procedure to date.
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Project description:Breast carcinoma with pulmonary metastasis can be treated locally or systemically. Following primary tumour resection patients with isolated, completely resectable pulmonary nodules and definite functional operability can be offered lung metastasis resection. Following metastasectomy a median survival of 32 to 96.6 months can be achieved with corresponding five-year survival rates between 30.8 and 54.4%. The procedure is associated with a mortality rate of 0 to 3%. The most important independent prognostic factor for long-term survival is complete resection of all lung lesions. The configuration and pattern of metastasis as well as disease-free interval, hormone and HER2/neu receptor status also appear to influence prognosis, but are of lesser importance. Intrapulmonary recurrence of metastases may, after careful selection on a case-by-case basis, also be treated operatively. In some cases this is associated with a favourable long-term prognosis. Pulmonary metastasectomy should be the treatment of choice for selected patients with metastatic breast carcinoma.
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Project description:Pulmonary metastasectomy (PM) is an established treatment that can provide improved long-term survival for patients with metastatic tumor(s) in the lung. In the current era, where treatment options other than PM such as stereotactic body radiation therapy (SBRT), immunotherapy, and molecular-targeted therapy are available, thoracic surgeons should review the approach to the preoperative evaluation and the indications. Preoperative evaluation consists of history and physical examinations, physiological tests, and radiological examinations. Radiological examinations serve to identify the differential diagnosis of the pulmonary nodules, evaluate their precise number, location, and features, and search for extra thoracic metastases. The indication of PM should be considered from both physiological and oncological points of view. The general criteria for PM are as follows; (I) the patient has a good general condition, (II) the primary malignancy is controlled, (III) there is no other extrapulmonary metastases, and (IV) the pulmonary lesion(s) are thought to be completely resectable. In addition to the general eligibility criteria of PM, prognostic factors of each tumor type should be considered when deciding the indication for PM. When patients have multiple poor prognostic factors and/or a short disease-free interval (DFI), thoracic surgeons should not hesitate to observe the patient for a certain period before deciding on the indication for PM. A multidisciplinary discussion is needed in order to decide the indication for PM.
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