腹腔溫熱化學療法 存活率達8成

[jesuischinoise]

http://tw.news.yahoo.com/article/url/d/ ... 1as5j.html

更新日期:2008/12/08 10:48 【中時健康 黃曼瑩／台北報導】
全台每年約有2474人死於胃癌，胃癌高居國人癌症死亡人數第4名，癌細胞的轉移往往令癌症病患對治療感到沮喪，尤其是胃腸癌病患。目前已經有醫院成功將「腹腔溫熱化學治療」應用在控制胃癌，5年存活率卻可達到83%以上，讓胃癌病患獲得有效控制，重新面對未來的人生。

由於胃腸有豐富淋巴引流系統，加上癌細胞浸潤胃壁的程度與轉移速度成正比，當癌症穿透胃腸壁時，更多了一種腹腔內轉移的方式，在傳統手術上，五年內病患的存活率不到30%。

正值中年的王小姐，從來不覺得胃有什麼不舒服，頂多就是覺得胃悶悶的，直到來萬芳醫院檢查，才發現自己竟然罹患胃癌(三期)，原先採用傳統的開刀方式切除癌細胞，但為了可以有效預防與控制住癌細胞的轉移，在萬芳醫院外科主任謝茂志醫師建議下，王小姐決定採用「腹腔溫熱化學療法」。王小姐於民國九十三年八月在萬芳醫院接受胃癌手術，術中發現胃腫瘤侵犯到胃漿膜外面為第3期，因為病人先生知道溫熱療法可以預防腹腔內轉移，所以主動要求在手術後十天立即再接受此手術，至今無轉移跡象。

「腹腔溫熱化學治療」方式已經發展二十餘年了，但是，國內仍不普遍的原因在於手術的時間長、危險性高，再加上知道如何施行的醫師寥寥可數，有設備的醫院更少，並且也沒有健保給付項目。甚至很多醫師都不知道國內可以施行。不過現在世界各國已有越來越多的國家投入這種治療。

　謝茂志醫師表示，腹腔內溫熱化學治療必須在手術中施行，在切除癌腫瘤後，於腹腔內灌注約攝氏42-43度的熱水，加上化學治療藥物，於腹腔內均勻分布維持一至二個小時，利用癌細胞對高溫的不耐性，以及高溫之下可以加強某些化學治療藥物的效果，藉以有效殺死癌細胞，並大大的提高病患存活率。治療中病患被全身麻醉，不會感覺到任何痛苦與不適。

中時健康：http://health.chinatimes.com/contents.a ... 15&id=3811

[blind faith]

J Clin Oncol. 2003 Oct 15;21(20):3737-43.

Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer

PURPOSE:
To confirm the findings from uncontrolled studies that aggressive cytoreduction in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) is superior to standard treatment in patients with peritoneal carcinomatosis of colorectal cancer origin.

PATIENTS AND METHODS:
Between February 1998 and August 2001, 105 patients were randomly assigned to receive either standard treatment consisting of systemic chemotherapy (fluorouracil-leucovorin) with or without palliative surgery, or experimental therapy consisting of aggressive cytoreduction with HIPEC, followed by the same systemic chemotherapy regime. The primary end point was survival.

RESULTS:
After a median follow-up period of 21.6 months, the median survival was 12.6 months in the standard therapy arm and 22.3 months in the experimental therapy arm (log-rank test, P =.032). The treatment-related mortality in the aggressive therapy group was 8%. Most complications from HIPEC were related to bowel leakage. Subgroup analysis of the HIPEC group showed that patients with 0 to 5 of the 7 regions of the abdominal cavity involved by tumor at the time of the cytoreduction had a significantly better survival than patients with 6 or 7 affected regions (log-rank test, P <.0001). If the cytoreduction was macroscopically complete (R-1), the median survival was also significantly better than in patients with limited (R-2a), or extensive residual disease (R-2b; log-rank test, P <.0001).

CONCLUSION:
Cytoreduction followed by HIPEC improves survival in patients with peritoneal carcinomatosis of colorectal origin. However, patients with involvement of six or more regions of the abdominal cavity, or grossly incomplete cytoreduction, had still a grave prognosis.

[blind faith]

後續的追蹤( 8 years) 報告:

Ann Surg Oncol. 2008 Sep;15(9):2426-32. Epub 2008 Jun 3.

8-year follow-up of randomized trial: cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy in patients with peritoneal carcinomatosis of colorectal cancer.

INTRODUCTION:
The treatment of peritoneal carcinomatosis is based on cytoreduction followed by hyperthermic intraperitoneal chemotherapy and combined with adjuvant chemotherapy. In 2003, a randomized trial was finished comparing systemic chemotherapy alone with cytoreduction followed by hyperthermic intraperitoneal chemotherapy and systemic chemotherapy. This trial showed a positive result favoring the studied treatment. This trial has now been updated to a minimal follow-up of 6 years to show long-term results.

PATIENTS AND METHODS:
For all patients still alive, the follow-up was updated until 2007. In the original study, four patients were excluded-two because of no eligible histology/pathology and two because of major protocol violations. After randomization, four patients in the HIPEC arm and six in the control arm were not treated using the intended therapy, one patient because of withdrawal, one because of a life-threatening other malignant disease and the others because of progressive disease before initiation of the treatment. During the follow-up, one patient was crossed over from the control arm and underwent cytoreduction and HIPEC for recurrent disease, after the assigned treatment was completed. The data from these patients were censored at the moment of the cross-over. Progression-free and disease-specific survival were analyzed using the Kaplan Meyer test and compared using the log rank method. The long-term results were studied in more detail to evaluate efficacy and toxicity.

RESULTS:
At the time of this update, the median follow-up was almost 8 years (range 72-115 months). In the standard arm, 4 patients were still alive, 2 with and 2 without disease; in the "HIPEC' arm, 5 patients were still alive, 2 with and 3 without disease. The median progression-free survival was 7.7 months in the control arm and 12.6 months in the HIPEC arm (P = 0.020). The median disease-specific survival was 12.6 months in the control arm and 22.2 months in the HIPEC arm (P = 0.028). The 5-year survival was 45% for those patients in whom a R1 resection was achieved.

CONCLUSION:
With 90% of all events having taken place up to this time, this randomized trial shows that cytoreduction followed by HIPEC does significantly add survival time to patients affected by peritoneal carcinomatosis of colorectal origin. For a selected group, there is a possibility of long-term survival.

[blind faith]

Eur J Surg Oncol. 2008 Nov;34(11):1246-52. Epub 2008 Jan 28.

Advanced gastric cancer with or without peritoneal carcinomatosis treated with hyperthermic intraperitoneal chemotherapy: a single western center experience.

INTRODUCTION: The aim of this article was to evaluate the role of hyperthermic intraperitoneal chemotherapy (HIPEC), associated or not to cytoreductive surgery (CS) in the treatment of different stages of advanced gastric cancer (AGC).

PATIENTS AND METHODS:
Thirty seven patients with AGC who underwent 43 HIPEC from June 1992 to February 2007 were included. HIPEC used Mitomycin-C and Cisplatin for 60-90 min at 41-43 degrees C intra-abdominal temperature. The main endpoints were long-term survivals, morbidity and mortality rates.

RESULTS:
Eleven patients had no demonstrable sign of PC and constituted the Prophylactic-group, while 26 patients had macroscopic PC (PC-group). Five patients were Gilly 1 or 2 (nodules <0.5 cm) and 21 Gilly 3 or 4 (nodules >or=0.5 cm). In the PC-group a complete curative CS was achieved before HIPEC in 8 (PC-curative subgroup) and a palliative HIPEC in 18 patients (PC-palliative subgroup). The overall 30-days mortality was 5% (2 patients). Two patients in the Prophylactic group died within 6 months after hospital discharge (overall mortality 11%). The estimated risk of death per procedure was 9%.Ten patients (27%) presented one or more complications. The median survival was 23.4 months in the Prophylactic group, and 6.6 months in the PC-group (p<0.05). The median survival in the PC-curative subgroup was 15 vs 3.9 months in the PC-palliative subgroup (p=0.007). The median survival according to Gilly classification was significantly different (Gilly 1&2 vs Gilly 3&4, 15 vs 4 months respectively, p=0.014). The global recurrence rates between the Prophylactic group and the PC-curative subgroup at 2years were 36% vs 50% respectively. The median delay to recurrence was 18.5 vs 9.7 months respectively.

CONCLUSION:
HIPEC might be useful to improve the survival in selected patients with ACG only when a complete cytoreduction can be achieved. Despite encouraging data, prospective studies, based on larger cohorts of patients are required to assess the role of this procedure as a prophylactic treatment in patients with AGC.

[blind faith]

Ann Surg Oncol. 2007 Oct;14(10):2702-13.

A systematic review and meta-analysis of the randomized controlled trials on adjuvant intraperitoneal chemotherapy for resectable gastric cancer.

BACKGROUND:
The purpose of this systematic review and meta-analysis was to determine the effectiveness and safety of adjuvant intraperitoneal chemotherapy for patients with locally advanced resectable gastric cancer.

METHODS:
Studies eligible for this systematic review included those in which patients with gastric cancer were randomly assigned to receive surgery combined with intraperitoneal chemotherapy versus surgery without intraperitoneal chemotherapy. There were no language restrictions. After independent quality assessment and data extraction, data were pooled for meta-analysis.

RESULTS:
Thirteen reports of randomized controlled trials (RCTs) were included for quality appraisal and data extraction. Ten reports were judged to be of fair quality and subjected to meta-analysis. A significant improvement in survival was associated with hyperthermic intraoperative intraperitoneal chemotherapy (HIIC) alone (hazard ratio [HR] = 0.60; 95% CI = 0.43 to 0.83; p = 0.002) or HIIC combined with early postoperative intraperitoneal chemotherapy (EPIC) (HR = 0.45; 95% CI = 0.29 to 0.68; p = 0.0002). There was a trend towards survival improvement with normothermic intraoperative intraperitoneal chemotherapy (p = 0.06), but this was not significant with either EPIC alone or delayed postoperative intraperitoneal chemotherapy. Intraperitoneal chemotherapy was also found to be associated with higher risks of intra-abdominal abscess (RR = 2.37; 95% CI = 1.32 to 4.26; p = 0.003) and neutropenia (RR = 4.33; 95% CI = 1.49 to 12.61; p = 0.007).

CONCLUSIONS:
The present meta-analysis indicates that HIIC with or without EPIC after resection of advanced gastric primary cancer is associated with improved overall survival. However, increased risk of intra-abdominal abscess and neutropenia are also demonstrated.

[blind faith]

1. survival time 並不等同治癒率 (cure rate) !
2. 大腸癌併單純只有腹膜轉移的, 相關 HIPC (Hyperthemic intra-peritoneal chemotherapy) 研究比較多.
(其實目前單用 systemic chemotherapy, survival time ~22 months 也差
不多)
3. 胃癌的post-operative intraperitoneal chemotherapy 在 meta-analysis 看
來有效, HIPC 看來有效一些.
但是也增加 2.37倍的 abscess 機會, 4.26倍的 neutropenia.
4. 重要的其實是需要把腫瘤清乾淨, 所以最少要R1 resection (microscopic
residual tumors)! 其中有些報告指出存活期也沒有比單用化學治療好多少!
反而以有腹膜轉移而開不乾淨的,作 HIPC的 survival time 更短!
要清乾淨,反而增加手術死者風險 ~10% mortality!!
5. 這樣鼓吹治癒率而沒說明相關風險, 又沒有健保給付條文 --- 難道是自費?
八成存活率? 這是那來的data ??
外國比較經驗豐富都有一成死亡率了, 真是藝高人膽大........

[梅花鹿]

經過7-8年，不知這方面進展如何?
有在做的大醫院很少?
不知是否成效不夠理想?

[chen0923]

http://www.daikinbio.com/
請參考 Whole-body Hyperthermia 可能更安全,更有效!!

[min]

(咦)

[blind faith]

https://www.facebook.com/groups/1190601040980105/