Advertisement

Hyperthermia in the Multimodal Therapy of Advanced Rectal Carcinomas

  • P. Wust
  • J. Gellermann
  • B. Rau
  • J. Löffel
  • A. Speidel
  • H. Stahl
  • H. Riess
  • T. J. Vogl
  • R. Felix
  • P. M. Schlag
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 142)

Abstract

The synergistic effects of hyperthermia (raising temperatures to 40°C and above) when combined with radiotherapy and cytotoxic drugs and a modulation of immunological phenomena have been demonstrated in the laboratory. Pre-clinical data relating to hyperthermia are summed up, along with their implications for clinical application. Controlled studies of local and regional hyperthermia have been performed during recent years, and these show us that the adjunction of hyperthermia provides at least an improvement of local control compared with radiotherapy alone. Current clinical results are summarized. Therapy systems based on radiowave irradiation have been commercially available for regional hyperthermia of the pelvis since the mid 1980s. This technology allows us to perform sufficiently tolerable and effective regional hyperthermia on rectal carcinomas. Used as part of curative preoperative and postoperative multimodal therapeutic strategies, hyperthermia can lead to improvement in local control (resectability, down-staging, progression-free time, recurrence rate), at least for certain risk groups. The preoperative radio-chemo-thermotherapy of advanced primary and recurring rectal carcinoma, uT3/4, was tested in a phase-I/II study of 20 patients. Therapy procedure, acute toxicity, thermal parameters, and response are described and discussed for this patient group. The regimen proved to be sufficiently tolerable, and complications did not occur. Tumor resection was performed on 14 of the 20 patients; 13 of the procedures were RO-resections and one was an R2 resection. In 64% of the resected rectal carcinomas, histopathological down-staging of the pretherapeutic endosonographical stadium was achieved; in three of the patients, despite continued non-resectability, local control has now been maintained for more than 12 months. In two patients with nonresectable rectal carcinomas, local progress was seen during the neoadjuvant combination therapy.

Keywords

Rectal Carcinoma Multimodal Therapy Thermal Dose Local Hyperthermia Regional Hyperthermia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ahmad NR, Marks G, Mohiuddin M (1993) High-dose preoperative radiation for cancer of the rectum: impact of radiation dose on patterns of failure and survival. Int J Radiat Oncol Biol Phys 27: 773–778PubMedCrossRefGoogle Scholar
  2. Al-Sarraf M (1988) Head and neck cancer: chemotherapy concepts. Semin Oncol 15: 70–85PubMedGoogle Scholar
  3. Arancia G, Malorni W, Mariutti G, Trovaluski P (1986) Effect of hyperthermia on the plasma membrane structure of Chinese hamster V79 fibroblasts: a quantitative freeze-fracture study. Radiat Res 106: 47–55PubMedCrossRefGoogle Scholar
  4. Arcangeli G, Arcangeli GC, Guerra A, Lovisolo G, Cividalli A, Marino C, Mauro F (1985) Tumour response to heat and radiation: prognostic variables in the treatment of neck node metastases from head and neck cancer. Int J Hyperthermia 1: 207–217PubMedCrossRefGoogle Scholar
  5. Basu O, Bierbass J (1994) HTHERM - hyperthermia program for processing BSD data. Contact author for copy, Fax-No.: 0201/7235–942Google Scholar
  6. Budach V, Dinges S, Stüben G, Unger A, Jahnke K, Sack H (1992) Simultaneous radio-chemotherapy of locally advanced ENT tumours - results of a pilot study. J Cancer Res Clin Oncol 118 [Suppl] (Abstract):2101Google Scholar
  7. Bull JMC (1984) An update on the anticancer effect of a combination of chemotherapy and hyperthermia. Cancer Res 44: 4853–4856Google Scholar
  8. Daly PF, Cohen JS (1989) Magnetic resonance spectroscopy of tumors and potential in vivo applications: a review. Cancer Res 49: 770–779PubMedGoogle Scholar
  9. Datta NR, Bose AK, Kapoor HK, Gupta S (1990) Head and neck cancers: results of thermoradiotherapy versus radiotherapy. Int J Hyperthermia 6: 479–486PubMedCrossRefGoogle Scholar
  10. DeLeeuw AAC, Lagendijk JJW (1987) Design of a clinical deep-body hyperthermia system based on the “coaxial TEM” applicator. Int J Hyperthermia 3: 413–421PubMedCrossRefGoogle Scholar
  11. Dewey WC, Hopwood LE, Sapareto SA, Gerweck LE (1977) Cellular responses to combinations of hyperthermia and radiation. Radiology 123: 463–474PubMedGoogle Scholar
  12. Dewey WC (1984) Interaction of heat with radiation and chemotherapy. Cancer Res 44: 4714–4720Google Scholar
  13. Dewey WC (1985) Mechanism of thermal radiosenzitation. In: Urano M, Douple E (eds) Biology of thermal potentiation of radiotherapy. VSP, Utrecht, pp 1–15Google Scholar
  14. Dikomey E, Eickhoff J, Jung H (1988) Effect of pH on development and decay of thermotolerance in CHO cells using fractionated heating at 43°C. Int J Hyperthermia 4: 555–565PubMedCrossRefGoogle Scholar
  15. Dische S (1989) Keynote address: hypoxic cell sensitizers: clinical developments. Int J Radiat Oncol Biol Phys 16: 1057–1060PubMedCrossRefGoogle Scholar
  16. Dische S, Saunders MI (1989) Continuous hyperfractionated, accelerated radiotherapy ( CHART ). Br J Cancer 59: 325–326Google Scholar
  17. Emami B, Song CW (1984) Physiological mechanisms in hyperthermia: a review. Int J Radiat (Nicol Biol Phys 10: 289–295CrossRefGoogle Scholar
  18. Engelhardt R (1987) Hyperthermia and drugs. In: Streffer C (ed) Hyperthermia and the therapy of malignant tumors. Springer, Berlin Heidelberg New York, pp 136–203Google Scholar
  19. Feldmann HJ, Molls M, Baumhoer W, Müller R-D, Sack H (1988) Radiatio and Hyperthermie in der Behandlung oberflächlicher and halbtiefer Tumoren. Wärmeprofile, Wärmedosen, Tumorrückbildung. Strahlenther Onkol 164: 602–609Google Scholar
  20. Feldmann HJ, Molls M, Heinemann H-G, Romanowski R, Stuschke M, Sack H (1993) Thermoradiotherapy in locally advanced deep-seated tumors — thermal parameters and treatment results. Radiother Oncol 26: 38–44PubMedCrossRefGoogle Scholar
  21. Fisher B, Wolmark N, Rockette H, Redmond C, Deutsch M, Wickerham DL, Fisher ER, Caplan R, Jones J, Lerner H, Gordon P, Feldmann M, Cruz A, Legault-Poisson S, Wexler M, Lawrence W, Robidoux A (1988) Postoperative adjuvant chemotherapy or radiation therapy for rectal cancer: results from NSABP protocol R-01. J Natl Cancer Inst 80: 21–29PubMedCrossRefGoogle Scholar
  22. Freeman ML, Holahan EV, Highfield DP, Raaphorst GP, Spiro IJ, Dewey WC (1981) The effect of pH on hyperthermic and X-ray induced cell killing. Int J Radiat Oncol Biol Phys 7: 211–216PubMedCrossRefGoogle Scholar
  23. Gastrointestinal Tumor Study Group (1985) Prolongation of the disease-free interval in surgically treated rectal carcinoma. N Engl J Med 312Google Scholar
  24. Gatenby RA, Kessler HB, Rosenblum JS, Coia LR, Moldofsky RJ, Hartz WH, Broder GJ (1989) Oxygen distribution in squamous cell carcinoma metastases and its relationship to outcome of radiation therapy. Int J Radiat Oncol Biol Phys 14: 831–838Google Scholar
  25. Gerweck LE (1988) Modifiers of thermal effects: environmental factors. In: Urano M, Douple E (eds) Thermal effects on cells and tissues. VSP, Utrecht 83–98Google Scholar
  26. Glaser F, Schlag P, Herfarth C (1990) Endorectal ultrasonography for the assessment of invasion of rectal tumors and lymph node involvement. Br J Surg 77: 883–887PubMedCrossRefGoogle Scholar
  27. Groveman DS, Borden EC, Merritt JA, Robins HI, Steeves RA, Bryan GT (1984) Augmented antiproliferative effects of interferons at elevated temperatures. Cancer Res 44: 5517–5521PubMedGoogle Scholar
  28. González González D (1994) ESHO 1–85: Radiotherapy versus radiotherapy plus hyperthermia in locally advanced breast cancer. Joint Meeting of the European Society for Radiation Biology and Hyperthermic Oncology, June 1–4, 1994, Abstracts, p 17Google Scholar
  29. Haim GM (1982) Hyperthermia and cancer. Plenum, New YorkGoogle Scholar
  30. Hahn GM, Shiu EC (1986) Adaption to low pH modifies thermal and thermo-chemical response of mammalian cells. Int J Hyperthermia 4: 379–388CrossRefGoogle Scholar
  31. Hall EJ, Roizin-Towle L (1984) Biological effects of heat. Cancer Res 44:4708–4713 Hall EJ ( 1988 ) Radiobiology for the radiologist. Lippincott, PhiladelphiaGoogle Scholar
  32. Hanson DF, Murphy PA, Silicano R, Shin HS (1983) The effect of temperature on the activation of thymocytes by interleukin 1 and 2. J Immunol 130 (1): 216–221PubMedGoogle Scholar
  33. Henderson IC, Harris JR, Kinne DW, Hellman S (1989) Cancer of the breast. In: DeVita VT, Hellman S, Rosenberg SA (eds) Cancer: principles and practice of oncology, 3rd edn. Lippincott, Philadelphia, pp 1242–1268Google Scholar
  34. Henk JM (1986) Late results of trial of hyperbaric oxygen and radiotherapy in head and neck cancer: a rationale for hypoxic cell sensitizers? Int J Radiat Oncol Biol Phys 12: 1339–1341PubMedCrossRefGoogle Scholar
  35. Henle KJ, Dethlefsen LA (1978) Heat fractionation and thermotolerance. A review. Cancer Res 38: 1843–1851Google Scholar
  36. Henle KJ, Roti-Roti JL (1988) Response of cultured mammalian cells to hyperthermia. VSP, Utredit, pp 57–82Google Scholar
  37. Herman TS, Teicher BA, Jochelson M, Clark J, Svensson G, Coleman CN (1988) Rationale for use of local hyperthermia with radiation therapy and selected anticancer drugs in locally advanced human malignancies. Int J Hyperthermia 4: 143–158PubMedCrossRefGoogle Scholar
  38. Herman TS, Jochelson MS, Teicher BA, Scott PJ, Hansen J, Clark JR, Pfeffer MR, Gelwan LE, Molnar-Griffin BJ, Fraser SM, Svennson G, Bornstein BA, Ryan L, Coleman CN (1989) A phase I-II trial of cisplatin, hyperthermia and radiation in patients with locally advanced malignancies. Int J Radiat Oncol Biol Phys 17: 1273–1279PubMedCrossRefGoogle Scholar
  39. Herman TS, Teicher BA, Holden SA (1990) Trimodality therapy (drug/hyperthermia/ radiation) with BCNU or mitomycin C. Int J Radiat Oncol Biol Phys 18: 375–382PubMedCrossRefGoogle Scholar
  40. Hoeckel M, Schlenger K, Knoop C, Vaupel P (1991) Oxygenation of carcinomas of the uterine cervix: evaluation by computerized 02 tension measurements. Cancer Res. 51: 3316–3322Google Scholar
  41. Hofman P, Knol RGF, Lagendijk JJW, Schipper J (1989) Thermoradiotherapy of primary breast carcinoma. Int J Hyperthermia 5: 1–11PubMedCrossRefGoogle Scholar
  42. Holahan EV, Highfield DP, Holahan PK, Dewey WC (1984) Hyperthermic killing and hyperthermic radiosensitization in Chinese hamster ovary cells: effects of pH and thermal tolerance. Radiat Res 97: 108–131PubMedCrossRefGoogle Scholar
  43. Issels RD, Prenninger SW, Nagele A, Boehm E, Sauer H, Jauch K-W, Denecke H, Berger H, Peter K, Wilmanns W (1990) Ifosfamide plus etoposide combined with regional hyperthermia in patients with locally advanced sarcomas: a phase-II study. J Clin Oncology 8: 1818–1829Google Scholar
  44. Issels RD, Mittermüller J, Gerl A, Simon W, Ortmaier A, Denzlinger C, Sauer H, Wilmanns W (1991) Improvement of local control by regional hyperthermia combined with systemic chemotherapy (ifosfamide plus etoposide) in advanced sarcomas: updated report on 65 patients. J Cancer Res Clin Oncol 117 [Suppl IV]: S141–S147PubMedCrossRefGoogle Scholar
  45. Issels RD (1995) Klinikum Großhadern, Department of Medical Oncology, Marchioninistr. 15, D–81337 München, Germany (Protocol)Google Scholar
  46. Jordan A, Wust P, Scholz R, Vogl T, Felix R (1996) Heat sensitivity of the human colonic adenocarcinoma cell lines WiDr and SW620. Int J Hyperthermia (in review) Jung H (1986) A generalized concept for cell killing by heat. Radiat Res 106: 56–72Google Scholar
  47. Jung H (1989) Step-down heating of CHO cells at 37.5–39°C. Int J Hyperthermia 5: 665–673PubMedCrossRefGoogle Scholar
  48. Jung H, Dikomey E, Zywietz F (1986) Ausmaß and zeitliche Entwicklung der Thermoresistenz and deren Einfluß auf die Strahlenempfindlichkeit von soliden Transplantationstumoren. In: Lokale Hyperthermie Streffer C, Herbst M, Schwabe H (eds) Deutscher Ärzte-Verlag, ColognerGoogle Scholar
  49. Jung H, Dikomey E (1987) Some basic effects in cellular thermobiology. In: Issels RD, Wilmanns W (eds) Application of hyperthermia in the treatment of cancer Springer, Berlin Heidelberg New York, pp 104–112Google Scholar
  50. Kapp DS (1986) Site and disease selection for hyperthermia clinical trials. Int J Hyperthermia 2: 139–156PubMedCrossRefGoogle Scholar
  51. Konsensus der CAO, AIO and ARO zur adjuvanten Therapie bei Kolon-and Rektumkarzinom vom 11.3. 1994. Onkologie 17: 291–293CrossRefGoogle Scholar
  52. Krook JE, Moertel CG, Gunderson LL, Wieand HS, Collins RT, Beart RW, Kubista TP, Poon MA, Meyers WC, Mailliard JA, Twito DI, Morton RF, Veeder MH, Witzig TE, Cha S, Vidyarthi S (1991) Effective surgical adjuvant therapy for highrisk rectal carcinoma. N Engl J Med 324Google Scholar
  53. Laszlo A, Wright W, Roti RJ (1992) Initial characterization of heat-induced excess nuclear proteins in HeLa cells. J Cell Physiol 151: 519–524PubMedCrossRefGoogle Scholar
  54. Leopold KA, Dewhirst MW, Sammulski TV, Dodge RK, George SL, Blivin JL, Prosnitz LR, Oleson JR (1993) Cumulative minutes with T90 greater than Temp,nae. is predictive of response of superficial malignancies to hyperthermia and radiation. Int J Radiat Oncol Biol Phys 25: 841–847PubMedCrossRefGoogle Scholar
  55. Lindegaard JC, Overgaard J (1987) Factors of importance for the development of the step-down heating effect in a C3H mammary carcinoma in vivo. Int J Hyperthermia 3: 79–91PubMedCrossRefGoogle Scholar
  56. Lindholm C-E, Kjellen E, Nilsson P, Hertzman S (1987) Microwave-induced hyperthermia and radiotherapy in human superficial tumours: clinical results with a comparative study of combined treatment versus radiotherapy alone. Int J Hyperthermia 3: 393–411PubMedCrossRefGoogle Scholar
  57. Lindquist S, Craig EA (1988) The heat shock proteins. Annu Rev Genet 22: 631–636PubMedCrossRefGoogle Scholar
  58. Mak AC, Rich TA, Schultheiss TE, Kavanagh B, Ota DM, Romsdahl MM (1994) Late complications of postoperative radiation therapy for cancer of the rectum and rectosigmoid. hit J Radiat Oncol Biol Phys 28: 597–603Google Scholar
  59. Meyer JL (1984) The clinical efficacy of localized hyperthermia. Cancer Res 44: 4745–4751Google Scholar
  60. Mendenhall WM, Million RR, Bova FJ (1984) Analysis of time-dose factors in clinically positive neck nodes treated with irradiation alone in squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 10: 639–643PubMedCrossRefGoogle Scholar
  61. Mills MD, Meyn RE (1981) Effects of hyperthermia on repair of radiation-induced DNA strand breaks. Radiat Res 87: 314–328PubMedCrossRefGoogle Scholar
  62. Mills MD, Meyn RE (1983) Hyperthermic potentiation of unrejoined DNA strand breaks following irradiation. Radiat Res 95: 327–338PubMedCrossRefGoogle Scholar
  63. Minsky BD, Kemeny N, Cohen AM, Enker WE, Kelsen DP, Reichman B, Saltz L, Sigurdson ER, Frankel J (1991) Preoperative high-dose leucovorin/5-fluoruracil and radiation therapy for unresectable rectal cancer. Cancer 67: 2859–2866PubMedCrossRefGoogle Scholar
  64. Minsky BD, Cohen AM, Kemeny N, Enker WE, Kelsen DP, Schwartz G, Saltz L, Dougherty J, Frankel J, Wiseberg J (1993) Pre-operative combined 5-FU low-dose leucovorin and sequential radiation therapy for unresectable rectal cancer. Int J Radiat Oncol Biol Phys 25: 821–827PubMedCrossRefGoogle Scholar
  65. Mohiuddin M, Ahmad N, Marks G (1993) A selective approach to adjunctive therapy for cancer of the rectum. Int J Radiat Oncol Biol Phys 27: 765–772PubMedCrossRefGoogle Scholar
  66. Molls M, Feldmann HJ (1991) Clinical investigations on blood flow in malignant tumors of the pelvis and the abdomen. In: Vaupel P, Jain RK (eds) Tumor blood supply and metabolic microenvironment: characterization and implications for therapy Fischer, Stuttgart, Funktionsanalyse biologischer Systeme Bd. 20, pp 143–153Google Scholar
  67. Molls M, Fink U (1994) Perioperative radiotherapy +/- chemotherapy in rectal cancer. Ann Oncol 5Google Scholar
  68. Mooibroek J, Dikomey E, Zywietz F (1988) Thermotolerance kinetics and growth rate changes in the R1H tumour heated at 43°C. Int J Hyperthermia 4: 677–686PubMedCrossRefGoogle Scholar
  69. Multhoff G, Botzler C, Wiesnet M, Issels RD (1994) Selective cell surface expression of an immunogenic determinant associated with a 72kd heat shock protein (HSP). Joint Meeting of the European Society for Radiation Biology and Hyperthermic Oncology, June 1–4, 1994, Abstracts, p 127Google Scholar
  70. Ng TC, Majors AW, Vijayakumar S et al (1989) Human neoplasm pH and response to radiation therapy: P–31 MR spectroscopy studies in situ. Radiology 170: 875–878PubMedGoogle Scholar
  71. Nielsen OS, Henle KJ, Overgaard J (1982) Arrhenius analysis of survival curves from thermotolerant and step-down heated L1A2 cells in vitro. Radiat Res 91: 468–482PubMedCrossRefGoogle Scholar
  72. Nielsen OS, Overgaard J, Kamura T (1983) Influence of thermotolerance on the interaction between hyperthermia and radiation in a solid tumour in vivo. Br J Radiology 56: 267–273CrossRefGoogle Scholar
  73. Niitsu Y, Watanabe N, Umeno H, Sone H, Neda H, Yamauchi N, Maeda M, Urushizaki I (1988) Synergistic effects of recombinant human tumor necrosis factor and hyperthermia on in vitro cytotoxicity and artificial metastasis. Cancer Res 48: 654–657PubMedGoogle Scholar
  74. Oleson JR, Sim DA, Manning MR (1984) Analysis of prognostic variables in hyperthermia treatment of 161 patients. Int J Radiat Oncol Biol Phys 10: 2231–2239PubMedCrossRefGoogle Scholar
  75. Overgaard(1980) Simultaneous and sequential hyperthermia and radiation treatment of an experimental tumor and its surrounding normal tissue in vivo. Int J Radiat Oncol Biol Phys 6:1507–1517Google Scholar
  76. Overgaard J (1981) Fractionated radiation and hyperthermia: experimental and clinical studies. Cancer 48: 1116–1123PubMedCrossRefGoogle Scholar
  77. Overgaard J (1987) Some problems related to the clinical use of thermal isoeffect doses. Int J Hyperthermia 3: 329–336PubMedCrossRefGoogle Scholar
  78. Overgaard J (1989) The current and potential role of hyperthermia in radiotherapy. Int J Radiat Oncol Biol Phys 16: 535–549PubMedCrossRefGoogle Scholar
  79. Overgaard J (1990) Clinical trials with hyperthermia and radiotherapy. In: Gautherie M (ed) Biological basis of oncologic thermotherapy. Springer, Berlin Heidelberg New York, pp 57–62Google Scholar
  80. Overgaard J (1994) ESHO 3–85: assessment of the efficacy of hyperthermia as adjuvant to radiation therapy in the treatment of metastatic malignant melanomas. Joint Meeting of European Societies of Radiation Biology (ESRB) and Hyperthermic Oncology (ESHO), 1–4 June 1994, Amsterdam, Abstract Book, p 19Google Scholar
  81. Perez CA, Kuske RR, Emami B, Fineberg B (1986) Irradiation alone or combined with hyperthermia in the treatment of recurrent carcinoma of the breast in the chest wall: a nonrandomized comparison. Int J Hyperthermia 2: 179–188PubMedCrossRefGoogle Scholar
  82. Perez CA, Emami B, Kuske RR, Hornback N, Pajak T, Kasdorf P (1989a): Irradiation and hyperthermia in the treatment of recurrent carcinoma of the breast in the chest wall MIR and RTOG experience. In: Sugahara T, Saito M (eds) Hyperthermic oncology 1988, vol 2, Taylor and Francis, London, 422–425Google Scholar
  83. Perez CA, Gillespie B, Pajak T, Hornback NB, Emami B, Rubin P (1989b) Quality assurance problems in clinical hyperthermia and their impact on therapeutic outcome: a report by the Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys 16: 551–558PubMedCrossRefGoogle Scholar
  84. Peters LJ, Ang KK, Thames HD (1988) Accelerated fractionation in the radiation treatment of head and neck cancer. Acta Oncologica 27: 185–194PubMedCrossRefGoogle Scholar
  85. Pilepich MV, Jones KG, Emami BN, Perez CA, Fields JN, Myerson RJ (1989) Interaction of bleomycin and hyperthermia - results of a clinical pilot study. Int J Radiat Oncol Biol Phys 16: 211–213PubMedCrossRefGoogle Scholar
  86. Reinhold HS, Endrich B (1986) Invited review: tumour microcirculation as a target for hyperthermia. Int J Hyperthermia 2: 111–137PubMedCrossRefGoogle Scholar
  87. Robins FIL, Cohen JD, Schmitt CL (1993) Phase I clinical trial of carboplatin and 41.8°C whole-body hyperthermia in cancer patients. J Clin Oncol 9: 1787–1794Google Scholar
  88. Roti-Roti JL, Winward RT (1978) The effects of hyperthermia on the protein-to-DNA ratio of isolated HeLa cell chromatin. Radiat Res 74: 159–169PubMedCrossRefGoogle Scholar
  89. Roti-Roti JL, Laszlo A (1988) The effects of hyperthermia on cellular macromolecules. In: Urano M, Douple E (eds) Thermal effects on cells and tissues. VSP, Utrecht, pp 13–56Google Scholar
  90. Rouesse J, Friedman S, Sevin DM et al (1987) Pre-operative induction chemotherapy in the treament of locally advanced soft tissue sarcomas. Cancer 60:296–301 Sapareto SA (1988) Practical concepts of thermal dose. In: Urano M, Douple E (eds) Thermal effects on cells and tissues. VSP, Utrecht, pp 201–212Google Scholar
  91. Sapozink MD (1986) The application of thermal dose in clinical trials. Int J Hyperthermia 2: 157–164PubMedCrossRefGoogle Scholar
  92. Sardi JF, DiPaola GR, Giaroli A, Sananes C, Rueda NG, Cachau A, Burlando S (1990) Results of a phase-II trial with neoadjuvant chemotherapy in carcinoma of the cervix uteri. Gynecol Oncol. 31: 245–261Google Scholar
  93. Scher HI (1990) Chemotherapy for invasive bladder cancer: neoadjuvant versus adjuvant. Sem Oncol 17: 555–565Google Scholar
  94. Schlag P, Riess H (1994) Virchow-Klinikum, Departments of Surgery and Medical Oncology, Lindenberger Weg 80, D–13122 Berlin, Germany (Protocol)Google Scholar
  95. Scott RS, Johnson RJR, Kowal H, Krishnamsetty M, Story K, Clay L (1983) Hyperthermia in combination with radiotherapy: a review of five years’ experience in the treatment of superficial tumors. Int J Radiat Oncol Biol Phys 9: 1327–1333PubMedCrossRefGoogle Scholar
  96. Scott R, Gillespie B, Perez CA, Hornback NB, Johnson R, Emami B, Bauer M, Pakuris E (1988) Hyperthermia in combination with definitive radiation therapy: results of a phase-I/II PTOG study. Int J Radiat Oncol Biol Phys 15: 711–716PubMedCrossRefGoogle Scholar
  97. Seebass M, Sullivan D, Wust P, Deuflhard P, Felix R (1993) The Berlin hyperthermia treatment planning program. Konrad-Zuse-Zentrum, Preprint SC 93–35Google Scholar
  98. Semmler W, Gademann G, Bachert-Baumann P, Zabel H-J, Lorenz WJ, Kaick G van (1988) Monitoring human tumor response to therapy by means of P-31 MR spectroscopy. Radiology 166: 533–539PubMedGoogle Scholar
  99. Shrivastava PN, Saylor TK, Matloubieh AY, Paliwal BR (1988) Hyperthermia quality assurance results. Int J Hyperthermia 4: 25–37PubMedCrossRefGoogle Scholar
  100. Song CW (1984) Effect of local hyperthermia on blood flow and microenvironment: a review. Cancer Research 44: 4721–4730Google Scholar
  101. Spiro IJ, Denman DL, Dewey WC (1982) Effects of hyperthermia on CHO DNA polymerases a and /3. Radiat Res 89: 134–149PubMedCrossRefGoogle Scholar
  102. Strauss LG (1991) Positron emission tomography (PET) for therapy management. In: Breit A (ed) Advanced radiation therapy: tumor response monitoring and treatment planning. Springer, Berlin Heidelberg New York, pp 25–28Google Scholar
  103. Streffer C (1985) Review: metabolic changes during and after hyperthermia. Int J Hyperthermia 1: 305–319PubMedCrossRefGoogle Scholar
  104. Streffer C, Beuningen D van (1987) The biological basis for tumour therapy by hyperthermia and radiation. In: Streffer C (ed) Hyperthermia and the therapy of malignant tumors. Springer, Berlin Heidelberg New York, pp 24–70Google Scholar
  105. Streffer C (1990) Biological basis of thermotherapy (with special reference to oncology), In: Gautherie M (ed) Biological basis of oncologic thermotherapy. Springer, Berlin Heidelberg New York, pp 1–71CrossRefGoogle Scholar
  106. Suit HD (1982) Potential for improving survival rates for the cancer patient by increasing the efficacy of treatment of the primary lesion. Cancer 50: 1227–1234PubMedCrossRefGoogle Scholar
  107. Thames HD, Hendry JH (1987) Fractionation in radiotherapy. Taylor and Francis,LondonGoogle Scholar
  108. Turner PF (1984) Regional hyperthermia with an annular phased array. IEEE Trans Biomed Eng 31: 106–114PubMedCrossRefGoogle Scholar
  109. Urbon J, Murthy AK, Taylor SG, Hendrickson FR, Lanzl LH (1990) Retrospective analysis of hyperthermia for use in the palliative treatment of cancer: a multi-modality evaluation. Int J Radiat Oncol Biol Phys 18: 155–163PubMedCrossRefGoogle Scholar
  110. Valdagni R, Amichetti M (1993) Report of long-term follow-up in a randomized trial comparing radiation therapy and radiation therapy plus hyperthermia to metastatic lymph nodes in stage-IV head and neck patients. Int J Radiat Oncol Biol Phys 28: 163–169Google Scholar
  111. Valdgni R, Amichetti M, Pani G (1988a) Radical radiation alone versus radical radiation plus microwave hyperthermia for N3 (TNM-UICC) neck nodes: a prospective randomized clinical trial. Int J Radiat Oncol Biol Phys 15: 13–24Google Scholar
  112. Valdagni R, Liu F-F, Kapp DS (1988b) Important prognostic factors influencing outcome of combined radiation and hyperthermia. Int J Radiat Oncol Biol Phys 15: 959–972PubMedCrossRefGoogle Scholar
  113. van Dijk JDP, Gonzales-Gonzales D, Blank LECM (1989) Deep local hyperthermia with a four aperture array system of large waveguide radiators. Results of simulation and clinical application. In: Hyperthermic oncology 1988, vol 1: Summary papers, Sugahara T, Saito M (eds) Taylor and Francis, London, pp 573–575Google Scholar
  114. van der Zee J, Treurniet-Donker AD, The SK, Helle PA, Seldenrath JJ, Meerwaldt JH, Wijaalen AJ, Berg AP, van den, Rhoon GC, van Broekmeyer-Reurink MP, Reinhold HS (1988) Low-dose reirradiation in combination with hyperthermia: a palliative treatment for patients with breast cancer in previously irradiated areas. Int J Radiat Oncol Biol Phys 15: 1407–1413Google Scholar
  115. van der Zee J, Broekmeyer-Reurink MP, Berg AP,Geel BN van, Jansen RFM, Kroon BBR, Wijk J van, Hagenbeek A (1989) Temperature distribution and pH changes during hyperthermic regional isolation perfusion. Eur J Cancer Clin Oncol 25: 1157–1163PubMedCrossRefGoogle Scholar
  116. van der Zee J, Gonzalez-Gonzalez D, van Putten WLJ, Hart AAM, Koper PCM, Treurniet-Donker AD, Wijnmaalen AJ, van Dijk JDP, van Rhoon GC (1993) Hyperthermia combined with radiotherapy in deep seated tumors-a phase III trial. In: Hyperthermia in clinical oncology, November 25–27, 1993, Book of Abstracts, p 41Google Scholar
  117. Vaupel P, Kallinowski F, Okunieff P (1989) Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review Cancer Res 49: 6449–6465Google Scholar
  118. Vaupel P (1990) Pathophysiological mechanisms of hyperthermia in cancer therapy. In: Gautherie M (ed) Biological bassis of oncologic thermotherapy Springer, Berlin Heidelberg New York, pp 73–134Google Scholar
  119. Vaupel P, Kallinowski F, Okunieff P (1989) Blood flow, oxygen and nutrient supply and metabolic microenvironment of human tumors: a review. Cancer Res 49: 6449–6465PubMedGoogle Scholar
  120. Vernon CC, van der Zee J, Lui FF (1994) Collaborative phase-III superficial hyperthermia trial. Joint Meeting of European Societies of Radiation Biology (ESRB) and Hyperthermic Oncology (ESHO), June 1–4, 1994, Amsterdam, Abstract Book, p 16Google Scholar
  121. Waterman FM, Nerlinger RE, Moylan DJ, Leeper DB (1987) Response of human tumor blood flow to local hyperthermia. Int J Radiat Oncol Biol Phys 13: 75–82PubMedGoogle Scholar
  122. Watson ER, Halnan KE, Dische S, Saunders MI, Code IS, McEwen JB, Wienik G, Perricis DJ, Sutherland I (1978) Hyperbaric oxygen and radiotherapy: a Medical Research Council trail in carcinoma of the cervix. Br J Radiol 51: 879–887PubMedCrossRefGoogle Scholar
  123. Wendt TG, Hartenstein RC, Wustrow TPU, Lissner J (1989) Cisplatin, flourouracil with leucovorin calcium enhancement, and synchronous accelerated radiotherapy in the management of locally advanced head and neck cancer: a phase-II study. J Clinical Oncology 7: 471–476Google Scholar
  124. Willett CG, Shellito PC, Tepper JE, Eliseo R, Convery K, Wood WC (1991) Intraoperative electron beam radiation therapy for recurrent locally advanced rectal or rectosigmoid carcinoma. Cancer 67: 1504–1508PubMedCrossRefGoogle Scholar
  125. Wilson GD, McNally NJ, Dische S, Saunders MI, Des Rochers C, Lewis AA, Bennett MH (1988) Measurement of cell kinetics in human tumours in vivo using bromodeoxyuridine incorporation and flow cytometry. Br J Cancer 58: 423–431PubMedCrossRefGoogle Scholar
  126. Wong RSL, Dewey WC (1982) Molecular studies on the hyperthermic inhibition of DNA synthesis in Chinese hamster ovary cells. Radiat Res 92: 370–395PubMedCrossRefGoogle Scholar
  127. Wust P, Fähling H, Jordan A, Nadobny J, Seebass J, Seebass M, Felix R (1994) Development and testing of SAR-visualizing phantoms for quality control in RF hyperthermia. Int J Hyperthermia 10: 127–142PubMedCrossRefGoogle Scholar
  128. Wust P, Stahl H, Löffel J, Seebass M, Riess H, Felix R (1995a) Clinical, physiological and anatomical determinants for temperature elevations in radiofrequency hyperthermia. Int J Hyperthermia 11: 151–167PubMedCrossRefGoogle Scholar
  129. Wust P, Seebass M, Nadobny J, Felix R (1995b) Electromagnetic deep heating technology. In: Seegenschmiedt MH, Fessenden P, Vernon CC (eds) Principles and practice of thermoradiotherapy and thermochemotherapy. Springer, Berlin Heidelberg New York: 219–251CrossRefGoogle Scholar
  130. Wust P, Meier T, Seebass M, Fähling H, Petermann K, Felix R (1995c) Noninvasive prediction of SAR distributions with an electro-optical E-field sensor. Int J Hyperthermia 11: 295–310PubMedCrossRefGoogle Scholar
  131. Wust P, Fähling Felix RH, Rahman S, Issels RD, Feldmann H, van Rhoon G, van der Zee J (1995d) Quality control of the SIGMA applicator using a lamp phantom: a four-center comparison. Int J Hyperthermia 11: 755–767PubMedCrossRefGoogle Scholar
  132. Wust P, Stahl H, Dieckmann K, Scheller S, Löffel J, Riess H, Jahnke V, Bier J, Felix R (1996a) Local hyperthermia of N2/N3 cervical lymph node metastases: correlation of technical and thermal parameters with response. Int J Radiat Oncol Biol Phys 34: 635–646PubMedCrossRefGoogle Scholar
  133. Wust P, Nadobny J, Seebass M, Deuflhard P, Mönich G, Felix R (1996b) Simulation studies promote technological development of phased-array radiofrequency hyperthermia. Int J Hyperthermia (in press)Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1996

Authors and Affiliations

  • P. Wust
    • 1
  • J. Gellermann
    • 1
  • B. Rau
    • 2
  • J. Löffel
    • 3
  • A. Speidel
    • 3
  • H. Stahl
    • 1
  • H. Riess
    • 3
  • T. J. Vogl
    • 2
  • R. Felix
    • 1
  • P. M. Schlag
    • 2
  1. 1.Department of Radiation OncologyRudolf Virchow University ClinicBerlinGermany
  2. 2.Department of Surgery, Robert-Rössle HospitalHumboldt UniversityBerlinGermany
  3. 3.Department of Medical OncologyRudolf Virchow University ClinicBerlinGermany

Personalised recommendations