Outcomes of FIGO Stage Ib-IVa Cervical Cancer With or Without Nodal Metastases After Radical Radiotherapy or Chemoirradiation
FMY Lim, KY Wong, ACK Cheng, CC Yau
Hong Kong J Radiol 2014;17:87-97
DOI: 10.12809/hkjr1413222
Objectives: Radical radiotherapy or chemoirradiation is the standard of care for International Federation of Gynecology and Obstetrics (FIGO) stage Ib-IVa cervical cancer. However, patients with pelvic or para-aortic nodal metastases have increased chance of recurrence and poor survival compared with those patients with no lymph node involvement. Their optimal management remains unclear. This study aimed at retrospectively evaluating the treatment outcomes of these patients in our unit to identify potential ways of improvement.
Methods: From May 2007 to December 2012, 137 consecutive patients with FIGO stage Ib-IVa cervical cancers were treated with radical radiotherapy or chemoirradiation. Radical radiotherapy consisted of whole-pelvic external radiotherapy (ERT) with a median dose of 50 Gy in 2 Gy per fraction (median shield after 40 Gy), high-dose-rate intracavitary brachytherapy (6.5 Gy/application for four or 7.7 Gy/application for three at Manchester point A, 2 applications/week) followed by additional external beam parametrial boost of 6 to 8 Gy, if indicated. Involved pelvic lymph nodes were boosted with a total dose of 60 to 64 Gy. Para-aortic nodal metastases were treated upfront by extended anteroposterior-posteroanterior field ERT covering both the para-aortic regions and the whole pelvis with a dose of 30 Gy in 2 Gy per fraction, followed by split-field 3-dimensional conformal boost of 20 Gy. Routine intracavitary brachytherapy, parametrial boost, and pelvic nodal boost were then given, when appropriate. Concurrent chemotherapy, when given, consisted of weekly cisplatin (40 mg/m2). Treatment outcome parameters including overall survival (OS), cancer-specific survival (CSS), relapse-free survival (RFS), and patterns of failure were evaluated in all patients. Survival data were compared with the log-rank test and prognostic factors were analysed with the Cox proportional hazards regression model.
Results: Of the 137 patients, 99 (72%) received chemoirradiation; 37 (27%) had either pelvic and / or para-aortic nodal metastases on radiological or pathological examination. After a median follow-up of 31 (range, 2-72) months, a significantly higher proportion of patients in group A (those with lymph node metastasis, 35%) had disease recurrence than in group B (those without lymph node metastasis, 19%; p = 0.047). Patients in group A had poorer 3-year OS (60%) and CSS (64%) compared with those in group B (OS, 75%, p = 0.08; CSS, 81%, p = 0.051) but the difference did not reach statistical significance. Patients in group A had significantly poorer 3-year RFS (50%) compared with those in group B (RFS, 73%; p = 0.009). FIGO stage III-IVa, presence of nodal metastases, and overall treatment time of more than 56 days were significant poor prognostic factors for both OS and RFS in multivariate analysis. Among patients with relapse, the majority (77% in group A and 84% in group B) developed first recurrence at distant sites with or without local relapse at a median time of 9.6 (range, 1.3-39.6) months. Only four (11%) patients in group A and five (5%) patients in group B developed first recurrence within the pelvis (pelvic control, 89% and 95%, respectively). Both radical radiotherapy and chemoirradiation were well-tolerated with no grade 3-4 acute toxicities. Only 4% (6/137) of patients developed grade 3-4 chronic toxicities (enterovaginal fistula, n=3; proctitis requiring surgery, n=2; cystitis with frequent haematuria, n=1). All four patients with para-aortic nodal metastases received extended-field chemoirradiation. Half died from distant metastases and the other half remained alive without recurrence. None of them developed grade 3 or 4 acute or chronic toxicities.
Conclusion: Radical radiotherapy and chemoirradiation were associated with high pelvic control rates (89-95%). However, distant recurrence remained the main reason of treatment failure, especially for those with advanced-stage disease (FIGO III-IVa) or nodal metastases. More effective treatment targeted at early systemic eradication of distant microscopic disease is a potential way to improve survival. Careful scheduling of systemic treatment into the radiotherapy course is also important in order not to jeopardise the highly effective pelvic control offered by radiotherapy.
中文摘要
FIGO分期Ib-IVa子宮頸癌（有或無淋巴結轉移）根治性放射治療或放射化學治療結果
林美瑩、黃家仁、鄭志堅、邱振中
目的： 按國際婦產科協會（FIGO）指南，根治性放射治療或放射化學治療是醫治分期Ib-IVa子宮頸癌的標準方案。然而，有盆腔或腹主動脈旁淋巴結轉移的患者復發機率增高，生存率較低，最佳治療方案不明確。本研究旨在回顧性評估這些患者在本院的治療結果，從而找出潛在的改善方法。
方法： 2007年5月至2012年12月期間，FIGO分期Ib-IVa子宮頸癌而接受根治性放射治療或放射化學治療的共有137例。根治性放療包括全盆腔外照射（ERT），每次2 Gy，總劑量中位數50 Gy（40 Gy後中央屏蔽），高劑量率腔內近距離放療（在曼徹斯特A點，每次應用6.5 Gy，共4次；或每次應用7.7 Gy，共3次；每週兩次）續以6-8 Gy的子宮旁外照射促進療效（如有指徵）。盆腔淋巴結轉移的病例總劑量升至60至64 Gy。主動脈旁淋巴結轉移病例則預先採用覆蓋主動脈旁區和整個盆腔的擴大範圍的前後-後前野ERT，每次2 Gy，總劑量30 Gy；續以20 Gy的分割三維適形放療強化。之後適當給予常規腔內近距離放療、子宮旁加強照射和盆腔淋巴結加強照射。如聯合化療，再包括每週一次的順鉑（40 mg/m2）。評估的療效參數包括總存活率、癌症特異性存活率、無復發存活率和失效模式。用log-rank檢驗比較生存數據，並用Cox比例風險回歸模型分析其預後因素。
結果：137名患者中，99名患者（72%）接受放射化學治療；根據放射或病理學結果，37名患者（27%）有盆腔和/或腹主動脈旁淋巴結轉移。在31個月（介乎2至72個月）的中位隨訪期之後，A組有淋巴結轉移患者的復發率（35%）明顯高出B組無淋巴結轉移的患者（19%，p = 0.047）。A組的三年總存活率（60%）和癌症特異性存活率（64%）均比B組差（三年總存活率75%，p = 0.080；癌症特異性存活率81%，p = 0.051），但差異未達到統計學意義。A組三年無復發存活率（50%）比B組（73%）顯著較差（p = 0.009）。在多變量分析中發現，FIGO分期III-Ⅳa、淋巴結轉移的存在、總治療期超過56天均為總存活率和無復發存活率的顯著預後不良因素。復發患者當中，大部分（A組的77%和B組的84%）出現首次遠處轉移的中位數時間為9.6個月（介乎1.3-39.6個月）。只有A組4名患者（11%）和B組5名患者（5%）盆腔內首次復發（盆腔復發控制率，分別為89%和95%）。兩組均對根治性放療和放射化學治療耐受性良好，沒有3-4級急性毒性反應。只有4%（137中的6名患者）出現3-4級的慢性毒性反應（腸陰道瘻管3例、直腸炎而需進行手術2例、膀胱炎而引發頻繁血尿1例）。有腹主動脈旁淋巴結轉移的全部4名患者均接受擴大範圍的放射化學治療。一半患者因遠處轉移死亡，另一半仍存活而沒有復發。沒有患者出現3級或4級的急性或慢性毒性反應。
結論：根治性放射治療和放射化學治療均與高盆腔控制率有關（89-95%）。然而，遠處復發仍然是治療失敗的主要原因，特別是對那些晚期疾病（FIGO分期Ⅲ-Ⅳa）或淋巴結轉移的患者。更有效地早期全身性根治遠處鏡下病灶是提高存活率的潛在方式。為了不降低放射治療對盆腔病變的高效控制，將全身性治療的精心計劃引入放射治療相當重要。