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Erschienen in: International Journal of Clinical Oncology 2/2018

13.11.2017 | Original Article

Selecting patients for hyperthermia combined with preoperative chemoradiotherapy for locally advanced rectal cancer

verfasst von: Sang-Won Kim, Ji Woon Yea, Jae Hwang Kim, Mi Jin Gu, Min Kyu Kang

Erschienen in: International Journal of Clinical Oncology | Ausgabe 2/2018

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Abstract

Background

This study investigated the role of hyperthermia combined with preoperative concurrent chemoradiotherapy (CCRT) for locally advanced rectal cancer (LARC) according to hypoxic marker expression.

Methods

One hundred and nine LARC patients with tissue blocks available for immunohistochemical assessment of carbonic anhydrase 9 (CA9) expression were reviewed. CA9 expression was considered positive when the staining percentage of tumor cells was >25% (n = 31). Pelvic radiotherapy with a total dose of 39.6–45 Gy was delivered concurrently with fluorouracil-based chemotherapy. Hyperthermia was administered to 52 patients twice a week during CCRT. Treatment response and outcomes were compared between hyperthermochemoradiotherapy (HCRT) and CCRT groups.

Results

In patients with positive CA9 expression, the rates of downstaging (p = 0.060) and pathologic complete response (p = 0.064) tended to be higher in the HCRT group than in the CCRT group. Distant metastasis-free survival (p = 0.029) and cancer-specific survival (p = 0.020) were significantly worse in tumors with both positive CA9 expression and poor tumor response. Negative CA9 expression, presence of major tumor response, and the use of hyperthermia were significant favorable prognostic factors for cancer-specific survival after the first recurrence in multivariate analysis.

Conclusions

Hyperthermia might selectively enhance the preoperative treatment response in LARC with positive CA9 expression and offset the negative effect of hypoxia on prognosis. Pretreatment evaluation of hypoxia could aid in the selection of patients who might benefit from hyperthermia.
Literatur
1.
Zurück zum Zitat Hildebrandt B, Wust P, Ahlers O et al (2002) The cellular and molecular basis of hyperthermia. Crit Rev Oncol Hematol 43:33–56CrossRefPubMed Hildebrandt B, Wust P, Ahlers O et al (2002) The cellular and molecular basis of hyperthermia. Crit Rev Oncol Hematol 43:33–56CrossRefPubMed
3.
Zurück zum Zitat Valentini V, Beets-Tan R, Borras JM et al (2008) Evidence and research in rectal cancer. Radiother Oncol 87:449–474CrossRefPubMed Valentini V, Beets-Tan R, Borras JM et al (2008) Evidence and research in rectal cancer. Radiother Oncol 87:449–474CrossRefPubMed
4.
Zurück zum Zitat Gunderson LL, Sargent DJ, Tepper JE et al (2004) Impact of T and N stage and treatment on survival and relapse in adjuvant rectal cancer: a pooled analysis. J Clin Oncol 22:1785–1796CrossRefPubMed Gunderson LL, Sargent DJ, Tepper JE et al (2004) Impact of T and N stage and treatment on survival and relapse in adjuvant rectal cancer: a pooled analysis. J Clin Oncol 22:1785–1796CrossRefPubMed
5.
Zurück zum Zitat Das P, Skibber JM, Rodriguez-Bigas MA et al (2006) Clinical and pathologic predictors of locoregional recurrence, distant metastasis, and overall survival in patients treated with chemoradiation and mesorectal excision for rectal cancer. Am J Clin Oncol 29:219–224CrossRefPubMed Das P, Skibber JM, Rodriguez-Bigas MA et al (2006) Clinical and pathologic predictors of locoregional recurrence, distant metastasis, and overall survival in patients treated with chemoradiation and mesorectal excision for rectal cancer. Am J Clin Oncol 29:219–224CrossRefPubMed
6.
Zurück zum Zitat Aschele C, Cionini L, Lonardi S et al (2011) Primary tumor response to preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer: pathologic results of the STAR-01 randomized phase III trial. J Clin Oncol 29:2773–2780CrossRefPubMed Aschele C, Cionini L, Lonardi S et al (2011) Primary tumor response to preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer: pathologic results of the STAR-01 randomized phase III trial. J Clin Oncol 29:2773–2780CrossRefPubMed
7.
Zurück zum Zitat Gerard JP, Azria D, Gourgou-Bourgade S et al (2012) Clinical outcome of the ACCORD 12/0405 PRODIGE 2 randomized trial in rectal cancer. J Clin Oncol 30:4558–4565CrossRefPubMed Gerard JP, Azria D, Gourgou-Bourgade S et al (2012) Clinical outcome of the ACCORD 12/0405 PRODIGE 2 randomized trial in rectal cancer. J Clin Oncol 30:4558–4565CrossRefPubMed
8.
Zurück zum Zitat Rodel C, Graeven U, Fietkau R et al (2015) Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 16:979–989CrossRefPubMed Rodel C, Graeven U, Fietkau R et al (2015) Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 16:979–989CrossRefPubMed
9.
Zurück zum Zitat Muthana M, Multhoff G, Pockley AG (2010) Tumour infiltrating host cells and their significance for hyperthermia. Int J Hyperthermia 26:247–255CrossRefPubMed Muthana M, Multhoff G, Pockley AG (2010) Tumour infiltrating host cells and their significance for hyperthermia. Int J Hyperthermia 26:247–255CrossRefPubMed
10.
Zurück zum Zitat Kang MK, Kim MS, Kim JH (2011) Clinical outcomes of mild hyperthermia for locally advanced rectal cancer treated with preoperative radiochemotherapy. Int J Hyperthermia 27:482–490CrossRefPubMed Kang MK, Kim MS, Kim JH (2011) Clinical outcomes of mild hyperthermia for locally advanced rectal cancer treated with preoperative radiochemotherapy. Int J Hyperthermia 27:482–490CrossRefPubMed
11.
Zurück zum Zitat van der Zee J, Gonzalez Gonzalez D, van Rhoon GC et al (2000) Comparison of radiotherapy alone with radiotherapy plus hyperthermia in locally advanced pelvic tumours: a prospective, randomised, multicentre trial. Dutch Deep Hyperthermia Group. Lancet 355:1119–1125CrossRefPubMed van der Zee J, Gonzalez Gonzalez D, van Rhoon GC et al (2000) Comparison of radiotherapy alone with radiotherapy plus hyperthermia in locally advanced pelvic tumours: a prospective, randomised, multicentre trial. Dutch Deep Hyperthermia Group. Lancet 355:1119–1125CrossRefPubMed
12.
Zurück zum Zitat Maluta S, Romano M, Dall’oglio S et al (2010) Regional hyperthermia added to intensified preoperative chemo-radiation in locally advanced adenocarcinoma of middle and lower rectum. Int J Hyperthermia 26:108–117CrossRefPubMed Maluta S, Romano M, Dall’oglio S et al (2010) Regional hyperthermia added to intensified preoperative chemo-radiation in locally advanced adenocarcinoma of middle and lower rectum. Int J Hyperthermia 26:108–117CrossRefPubMed
13.
Zurück zum Zitat Yea JW (2014) Postoperative complications after preoperative chemoradiotherapy combined with hyperthermia in locally advanced rectal cancer. Prog Med Phys 25:89–94CrossRef Yea JW (2014) Postoperative complications after preoperative chemoradiotherapy combined with hyperthermia in locally advanced rectal cancer. Prog Med Phys 25:89–94CrossRef
14.
Zurück zum Zitat Korkeila E, Talvinen K, Jaakkola PM et al (2009) Expression of carbonic anhydrase IX suggests poor outcome in rectal cancer. Br J Cancer 100:874–880CrossRefPubMedPubMedCentral Korkeila E, Talvinen K, Jaakkola PM et al (2009) Expression of carbonic anhydrase IX suggests poor outcome in rectal cancer. Br J Cancer 100:874–880CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat Guedj N, Bretagnol F, Rautou PE et al (2011) Predictors of tumor response after preoperative chemoradiotherapy for rectal adenocarcinomas. Hum Pathol 42:1702–1709CrossRefPubMed Guedj N, Bretagnol F, Rautou PE et al (2011) Predictors of tumor response after preoperative chemoradiotherapy for rectal adenocarcinomas. Hum Pathol 42:1702–1709CrossRefPubMed
16.
Zurück zum Zitat Nordsmark M, Overgaard M, Overgaard J (1996) Pretreatment oxygenation predicts radiation response in advanced squamous cell carcinoma of the head and neck. Radiother Oncol 41:31–39CrossRefPubMed Nordsmark M, Overgaard M, Overgaard J (1996) Pretreatment oxygenation predicts radiation response in advanced squamous cell carcinoma of the head and neck. Radiother Oncol 41:31–39CrossRefPubMed
17.
Zurück zum Zitat Ji RC (2014) Hypoxia and lymphangiogenesis in tumor microenvironment and metastasis. Cancer Lett 346:6–16CrossRefPubMed Ji RC (2014) Hypoxia and lymphangiogenesis in tumor microenvironment and metastasis. Cancer Lett 346:6–16CrossRefPubMed
18.
Zurück zum Zitat Sugihara K, Kusunoki M, Watanabe T et al (2009) Japanese classification of colorectal carcinoma. Japanese Society for Cancer of the Colon and Rectum, Kanehara Sugihara K, Kusunoki M, Watanabe T et al (2009) Japanese classification of colorectal carcinoma. Japanese Society for Cancer of the Colon and Rectum, Kanehara
19.
Zurück zum Zitat Datta NR, Ordonez SG, Gaipl US et al (2015) Local hyperthermia combined with radiotherapy and-/or chemotherapy: recent advances and promises for the future. Cancer Treat Rev 41:742–753CrossRefPubMed Datta NR, Ordonez SG, Gaipl US et al (2015) Local hyperthermia combined with radiotherapy and-/or chemotherapy: recent advances and promises for the future. Cancer Treat Rev 41:742–753CrossRefPubMed
20.
Zurück zum Zitat Kido Y, Kuwano H, Maehara Y et al (1991) Increased cytotoxicity of low-dose, long-duration exposure to 5-fluorouracil of V-79 cells with hyperthermia. Cancer Chemother Pharmacol 28:251–254PubMed Kido Y, Kuwano H, Maehara Y et al (1991) Increased cytotoxicity of low-dose, long-duration exposure to 5-fluorouracil of V-79 cells with hyperthermia. Cancer Chemother Pharmacol 28:251–254PubMed
21.
Zurück zum Zitat Maeta M, Sawata T, Kaibara N (1993) Effects of hyperthermia on the metabolism of 5-fluorouracil in vitro. Int J Hyperthermia 9:105–113CrossRefPubMed Maeta M, Sawata T, Kaibara N (1993) Effects of hyperthermia on the metabolism of 5-fluorouracil in vitro. Int J Hyperthermia 9:105–113CrossRefPubMed
22.
Zurück zum Zitat Rau B, Wust P, Hohenberger P et al (1998) Preoperative hyperthermia combined with radiochemotherapy in locally advanced rectal cancer: a phase II clinical trial. Ann Surg 227:380–389CrossRefPubMedPubMedCentral Rau B, Wust P, Hohenberger P et al (1998) Preoperative hyperthermia combined with radiochemotherapy in locally advanced rectal cancer: a phase II clinical trial. Ann Surg 227:380–389CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Asao T, Sakurai H, Harashima K et al (2006) The synchronization of chemotherapy to circadian rhythms and irradiation in pre-operative chemoradiation therapy with hyperthermia for local advanced rectal cancer. Int J Hyperthermia 22:399–406CrossRefPubMed Asao T, Sakurai H, Harashima K et al (2006) The synchronization of chemotherapy to circadian rhythms and irradiation in pre-operative chemoradiation therapy with hyperthermia for local advanced rectal cancer. Int J Hyperthermia 22:399–406CrossRefPubMed
24.
Zurück zum Zitat Shioya M, Takahashi T, Ishikawa H et al (2011) Expression of hypoxia-inducible factor 1alpha predicts clinical outcome after preoperative hyperthermo-chemoradiotherapy for locally advanced rectal cancer. J Radiat Res 52:821–827CrossRefPubMed Shioya M, Takahashi T, Ishikawa H et al (2011) Expression of hypoxia-inducible factor 1alpha predicts clinical outcome after preoperative hyperthermo-chemoradiotherapy for locally advanced rectal cancer. J Radiat Res 52:821–827CrossRefPubMed
25.
Zurück zum Zitat Schroeder C, Gani C, Lamprecht U et al (2012) Pathological complete response and sphincter-sparing surgery after neoadjuvant radiochemotherapy with regional hyperthermia for locally advanced rectal cancer compared with radiochemotherapy alone. Int J Hyperthermia 28:707–714CrossRefPubMed Schroeder C, Gani C, Lamprecht U et al (2012) Pathological complete response and sphincter-sparing surgery after neoadjuvant radiochemotherapy with regional hyperthermia for locally advanced rectal cancer compared with radiochemotherapy alone. Int J Hyperthermia 28:707–714CrossRefPubMed
26.
Zurück zum Zitat Shoji H, Motegi M, Osawa K et al (2015) A novel strategy of radiofrequency hyperthermia (neothermia) in combination with preoperative chemoradiotherapy for the treatment of advanced rectal cancer: a pilot study. Cancer Med 4:834–843CrossRefPubMedPubMedCentral Shoji H, Motegi M, Osawa K et al (2015) A novel strategy of radiofrequency hyperthermia (neothermia) in combination with preoperative chemoradiotherapy for the treatment of advanced rectal cancer: a pilot study. Cancer Med 4:834–843CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Maas M, Nelemans PJ, Valentini V et al (2010) Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol 11:835–844CrossRefPubMed Maas M, Nelemans PJ, Valentini V et al (2010) Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol 11:835–844CrossRefPubMed
28.
Zurück zum Zitat Kato Y, Yashiro M, Noda S et al (2010) Expression of a hypoxia-associated protein, carbonic anhydrase-9, correlates with malignant phenotypes of gastric carcinoma. Digestion 82:246–251CrossRefPubMed Kato Y, Yashiro M, Noda S et al (2010) Expression of a hypoxia-associated protein, carbonic anhydrase-9, correlates with malignant phenotypes of gastric carcinoma. Digestion 82:246–251CrossRefPubMed
29.
Zurück zum Zitat Lee S, Shin HJ, Han IO et al (2007) Tumor carbonic anhydrase 9 expression is associated with the presence of lymph node metastases in uterine cervical cancer. Cancer Sci 98:329–333CrossRefPubMed Lee S, Shin HJ, Han IO et al (2007) Tumor carbonic anhydrase 9 expression is associated with the presence of lymph node metastases in uterine cervical cancer. Cancer Sci 98:329–333CrossRefPubMed
30.
Zurück zum Zitat Janssen HL, Haustermans KM, Balm AJ et al (2005) Hypoxia in head and neck cancer: how much, how important? Head Neck 27:622–638CrossRefPubMed Janssen HL, Haustermans KM, Balm AJ et al (2005) Hypoxia in head and neck cancer: how much, how important? Head Neck 27:622–638CrossRefPubMed
31.
Zurück zum Zitat Lee-Kong SA, Ruby JA, Chessin DB et al (2012) Hypoxia-related proteins in patients with rectal cancer undergoing neoadjuvant combined modality therapy. Dis Colon Rectum 55:990–995CrossRefPubMed Lee-Kong SA, Ruby JA, Chessin DB et al (2012) Hypoxia-related proteins in patients with rectal cancer undergoing neoadjuvant combined modality therapy. Dis Colon Rectum 55:990–995CrossRefPubMed
33.
Zurück zum Zitat Chen T, Guo J, Han C et al (2009) Heat shock protein 70, released from heat-stressed tumor cells, initiates antitumor immunity by inducing tumor cell chemokine production and activating dendritic cells via TLR4 pathway. J Immunol 182:1449–1459CrossRefPubMed Chen T, Guo J, Han C et al (2009) Heat shock protein 70, released from heat-stressed tumor cells, initiates antitumor immunity by inducing tumor cell chemokine production and activating dendritic cells via TLR4 pathway. J Immunol 182:1449–1459CrossRefPubMed
34.
Zurück zum Zitat Dayanc BE, Beachy SH, Ostberg JR et al (2008) Dissecting the role of hyperthermia in natural killer cell mediated anti-tumor responses. Int J Hyperthermia 24:41–56CrossRefPubMed Dayanc BE, Beachy SH, Ostberg JR et al (2008) Dissecting the role of hyperthermia in natural killer cell mediated anti-tumor responses. Int J Hyperthermia 24:41–56CrossRefPubMed
35.
Zurück zum Zitat Noessner E, Gastpar R, Milani V et al (2002) Tumor-derived heat shock protein 70 peptide complexes are cross-presented by human dendritic cells. J Immunol 169:5424–5432CrossRefPubMed Noessner E, Gastpar R, Milani V et al (2002) Tumor-derived heat shock protein 70 peptide complexes are cross-presented by human dendritic cells. J Immunol 169:5424–5432CrossRefPubMed
36.
Zurück zum Zitat Gasser S, Orsulic S, Brown EJ et al (2005) The DNA damage pathway regulates innate immune system ligands of the NKG2D receptor. Nature 436:1186–1190CrossRefPubMedPubMedCentral Gasser S, Orsulic S, Brown EJ et al (2005) The DNA damage pathway regulates innate immune system ligands of the NKG2D receptor. Nature 436:1186–1190CrossRefPubMedPubMedCentral
37.
Zurück zum Zitat Kulzer L, Rubner Y, Deloch L et al (2014) Norm- and hypo-fractionated radiotherapy is capable of activating human dendritic cells. J Immunotoxicol 11:328–336CrossRefPubMed Kulzer L, Rubner Y, Deloch L et al (2014) Norm- and hypo-fractionated radiotherapy is capable of activating human dendritic cells. J Immunotoxicol 11:328–336CrossRefPubMed
38.
Zurück zum Zitat Kim JY, Son YO, Park SW et al (2006) Increase of NKG2D ligands and sensitivity to NK cell-mediated cytotoxicity of tumor cells by heat shock and ionizing radiation. Exp Mol Med 38:474–484CrossRefPubMed Kim JY, Son YO, Park SW et al (2006) Increase of NKG2D ligands and sensitivity to NK cell-mediated cytotoxicity of tumor cells by heat shock and ionizing radiation. Exp Mol Med 38:474–484CrossRefPubMed
39.
Zurück zum Zitat Schildkopf P, Frey B, Ott OJ et al (2011) Radiation combined with hyperthermia induces HSP70-dependent maturation of dendritic cells and release of pro-inflammatory cytokines by dendritic cells and macrophages. Radiother Oncol 101:109–115CrossRefPubMed Schildkopf P, Frey B, Ott OJ et al (2011) Radiation combined with hyperthermia induces HSP70-dependent maturation of dendritic cells and release of pro-inflammatory cytokines by dendritic cells and macrophages. Radiother Oncol 101:109–115CrossRefPubMed
40.
Zurück zum Zitat Frey B, Rubner Y, Wunderlich R et al (2012) Induction of abscopal anti-tumor immunity and immunogenic tumor cell death by ionizing irradiation − implications for cancer therapies. Curr Med Chem 19:1751–1764CrossRefPubMed Frey B, Rubner Y, Wunderlich R et al (2012) Induction of abscopal anti-tumor immunity and immunogenic tumor cell death by ionizing irradiation − implications for cancer therapies. Curr Med Chem 19:1751–1764CrossRefPubMed
41.
Zurück zum Zitat Goethals L, Debucquoy A, Perneel C et al (2006) Hypoxia in human colorectal adenocarcinoma: comparison between extrinsic and potential intrinsic hypoxia markers. Int J Radiat Oncol Biol Phys 65:246–254CrossRefPubMed Goethals L, Debucquoy A, Perneel C et al (2006) Hypoxia in human colorectal adenocarcinoma: comparison between extrinsic and potential intrinsic hypoxia markers. Int J Radiat Oncol Biol Phys 65:246–254CrossRefPubMed
Metadaten
Titel
Selecting patients for hyperthermia combined with preoperative chemoradiotherapy for locally advanced rectal cancer
verfasst von
Sang-Won Kim
Ji Woon Yea
Jae Hwang Kim
Mi Jin Gu
Min Kyu Kang
Publikationsdatum
13.11.2017
Verlag
Springer Japan
Erschienen in
International Journal of Clinical Oncology / Ausgabe 2/2018
Print ISSN: 1341-9625
Elektronische ISSN: 1437-7772
DOI
https://doi.org/10.1007/s10147-017-1213-z

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