The Christie NHS Foundation Trust, Manchester, UK.
The Christie NHS Foundation Trust, Manchester, UK ; The University of Manchester, Manchester, UK.
J Immunother Cancer. 2016 Oct 18;4:67. doi: 10.1186/s40425-016-0174-5. eCollection 2016.
VEGF-targeted therapy has become the mainstay of treatment for majority of mRCC patients. For most patients, benefit is short-lived and therefore treatment remains palliative in intent. HD IL2 is an effective immunotherapy treatment capable of durable remission in some patients but its unselected use has been difficult due to its modest response rate and considerable adverse effects. Using set pathology criteria as a selection tool in clinical practice, we have been able to show improved outcomes in our previous report. Here, we present an updated and extended report of this treatment and seek to explore any pathological, clinical and treatment variables likely to predict better outcomes.
This is an extension of a previously reported clinical audit, which includes mRCC cases treated with HD IL2 between 2003 and 2013. Since 2006, tumour specimens of potential candidates were routinely reviewed prospectively and stratified into or categories based on constitution of histological growth pattern, namely alveolar or solid versus papillary and/or sarcomatoid architecture; clear cell versus granular cell cytoplasmic morphology. HD IL2 was preferentially offered to patients with pathology. Outcome evaluation includes response rates, survival, and treatment tolerance. Multivariate analysis was performed to explore potential prognostic and predictive factors.
Among prospectively selected patients with pathology ( = 106), overall response rate was 48.1 % (51/106) with CR rate of 21.6 % (23/106). Median OS was 58.1 months. Factors associated with significantly better response and/or survival includes favourable pathology pattern, higher cycle 1 tolerance and lower number of metastatic organ sites (<3). CAIX (Carbonic anhydrase 9) has prognostic value but is not predictive of response. Toxicities were those expected of IL2 but were manageable on general medical wards, with no treatment-related death. Importantly most complete responses were durable with 76 % (23/30) cases remained relapse-free (median 39 months follow up) and 2 of the seven who relapsed had had long-term disease free survival after resection of oligometastatic relapse.
Our experience shows that HD IL2 remains an effective and safe treatment in well-selected cases of mRCC. The result in this single-institution patient series confirms similar outcomes to our previously reported retrospective series. Given the prospect of long-term remission, fit patients with histology and low disease burden should be considered for HD IL2 in an experienced centre. Better understanding has been gained from this in-depth analysis especially the examination of possible response predictors and strategies that can improve treatment outcome.
VEGF 靶向治疗已成为大多数 mRCC 患者的主要治疗方法。对于大多数患者，获益是短暂的，因此治疗仍然是姑息性的。HDIL2 是一种有效的免疫治疗方法，能够使一些患者获得持久缓解，但由于其反应率较低且不良反应较大，因此难以广泛应用。我们在之前的报告中使用设定的病理学标准作为临床实践中的选择工具，已经能够显示出更好的结果。在这里，我们报告了这项治疗的更新和扩展报告，并试图探讨任何可能预测更好结果的病理学、临床和治疗变量。
这是之前报道的临床审计的扩展，其中包括 2003 年至 2013 年间接受 HDIL2 治疗的 mRCC 病例。自 2006 年以来，对潜在候选者的肿瘤标本进行了前瞻性常规审查，并根据组织学生长模式的组成分为 或 类别，即肺泡或实体与乳头状和/或肉瘤样结构；透明细胞与颗粒细胞质形态。HDIL2 优先提供给具有 病理学的患者。结果评估包括反应率、生存率和治疗耐受性。进行了多变量分析以探讨潜在的预后和预测因素。
在具有前瞻性选择的 病理学患者中（ = 106），总缓解率为 48.1%（51/106），完全缓解率为 21.6%（23/106）。中位 OS 为 58.1 个月。与更好的反应和/或生存相关的因素包括有利的病理学模式、更高的第 1 周期耐受性和更少的转移器官部位（<3）。CAIX（碳酸酐酶 9）具有预后价值，但不能预测反应。毒性是 IL2 预期的毒性，但在普通医疗病房可以管理，没有治疗相关的死亡。重要的是，大多数完全缓解是持久的，76%（23/30）的病例无复发（中位随访 39 个月），7 例复发中有 2 例在寡转移复发后切除后长期无疾病生存。
我们的经验表明，HDIL2 仍然是一种有效和安全的治疗方法，适用于精心选择的 mRCC 病例。本机构患者系列的结果与我们之前报道的回顾性系列相似。鉴于长期缓解的前景，具有 组织学和低疾病负担的合适患者应在有经验的中心考虑接受 HDIL2 治疗。通过这种深入分析，我们获得了更好的理解，特别是对可能的反应预测因子的检查和可以改善治疗结果的策略。
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