First results of triple‐modality treatment combining radiotherapy, chemotherapy, and hyperthermia for the treatment of patients with Stage IIB, III, and IVA cervical carcinoma

Cancer (Impact Factor: 5.2). 08/2005; 104(4):763 - 770. DOI: 10.1002/cncr.21128
Source: PubMed

Patients with advanced cervical carcinoma are treated routinely with radiotherapy and cisplatin-containing chemotherapy. It has been shown that hyperthermia can improve the results of both radiotherapy and cisplatin. In the current study, the feasibility and efficacy of the combination of all three modalities was studied in previously untreated patients with cervical carcinoma.METHODS
Patients with advanced cervical carcinoma were registered prospectively in the U.S., Norway, and the Netherlands. External-beam radiotherapy and brachytherapy were administered for a biologically effective dose ≥ 86.7 gray. At least 4 courses of weekly cisplatin (40 mg/m2) and 4 sessions of weekly locoregional hyperthermia were added to radiotherapy.RESULTSSixty-eight patients with a median age of 45 years were enrolled. Full-dose radiotherapy was delivered to all patients according to plan. At least 4 courses of chemotherapy were received by 97% of patients, and at least 4 courses of hyperthermia treatment were received by 93% of patients. Toxicity was fully comparable to that described for chemoradiotherapy alone, and the median total treatment time was 45 days. Complete remission was achieved by 61 patients (90%). After a median follow-up of 538 days, 74% of patients remained alive without signs of recurrence, and the overall survival rate was 84%.CONCLUSIONS
The combination of full-dose radiotherapy, chemotherapy, and hyperthermia was feasible and effective in a multicenter international setting among patients with advanced cervical carcinoma. A Phase III study comparing this novel triplet with standard chemoradiation, designed to show at least a 15% improvement in overall survival, has been launched. Cancer 2005. © 2005 American Cancer Society.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Advanced uterine leiomyosarcoma (LMS) is a rare and extremely aggressive disease. In patients with advanced and unresected uterine LMS, multidisciplinary therapy is the best treatment option, although no consensus exists on the efficacy of the treatment. The present study describes the case of a 41-year-old female who underwent laparotomy due to a large uterine tumor. Exploratory laparotomy revealed a large tumor that had extended from the pelvic wall to the outside of the pelvis and then invaded the colon. Large residual tumors remained present in the pelvis following suboptimal debulking surgery. Subsequent to surgery, the patient was treated with adjuvant radiotherapy, followed by chemotherapy with regional whole pelvis hyperthermia (HT). Computed tomography revealed stable disease prior and subsequent to combination treatment. While treatment was being administered for third/fourth-degree burns and subcutaneous fatty necrosis, the patient developed multi-organ failure and succumbed. The present case report describes the potential for using a combination of chemotherapy, HT and radiotherapy in patients with LMS. The development of an effective protocol is required for the administration of chemotherapy, HT and radiotherapy in patients with advanced unresected LMS.
    Oncology letters 08/2014; 8(2):637-641. · 0.24 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The major problem of current drug-based therapy is selectivity. As in other areas of science, a combined approach might improve the situation decisively. The idea is to use the pro-drug principle together with an alternating magnetic field as physical stimulus, which can be applied in a spatially and temporarily controlled manner. As a proof of principle, the neutral hydrolysis of aspirin in physiological phosphate buffer of pH 7.5 at 40 degrees C was chosen. The sensor and actuator system is a commercially available gold nanoparticle (NP) suspension which is approved for animal usage, stable in high concentrations and reproducibly available. Applying the alternating magnetic field of a conventional NMR magnet system accelerated the hydrolysis of aspirin in solution.
    Nanoscale Research Letters 01/2009; 4(8):854-857. · 2.52 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The clinical success of hyperthermia adjunct to radiotherapy depends on adequate temperature elevation in the tumor with minimal temperature rise in organs at risk. Existing technologies for thermal treatment of the cervix have limited spatial control or rapid energy falloff. The objective of this work is to develop an endocervical applicator using a linear array of multisectored tubular ultrasound transducers to provide 3-D conformal, locally targeted hyperthermia concomitant to radiotherapy in the uterine cervix. The catheter-based device is integrated within a HDR brachytherapy applicator to facilitate sequential and potentially simultaneous heat and radiation delivery. Treatment planning images from 35 patients who underwent HDR brachytherapy for locally advanced cervical cancer were inspected to assess the dimensions of radiation clinical target volumes (CTVs) and gross tumor volumes (GTVs) surrounding the cervix and the proximity of organs at risk. Biothermal simulation was used to identify applicator and catheter material parameters to adequately heat the cervix with minimal thermal dose accumulation in nontargeted structures. A family of ultrasound applicators was fabricated with two to three tubular transducers operating at 6.6-7.4 MHz that are unsectored (360 degrees), bisectored (2 x 180 degrees), or trisectored (3 x 120 degrees) for control of energy deposition in angle and along the device length in order to satisfy anatomical constraints. The device is housed in a 6 mm diameter PET catheter with cooling water flow for endocervical implantation. Devices were characterized by measuring acoustic efficiencies, rotational acoustic intensity distributions, and rotational temperature distributions in phantom. The CTV in HDR brachytherapy plans extends 20.5 +/- 5.0 mm from the endocervical tandem with the rectum and bladder typically <8 mm from the target boundary. The GTV extends 19.4 +/- 7.3 mm from the tandem. Simulations indicate that for 60 min treatments the applicator can heat to 41 degrees C and deliver > 5EM(43 degrees C) over 4-5 cm diameter with Tmax < 45 degrees C and 1 kg m(-3) s(-1) blood perfusion. The 41 degrees C contour diameter is reduced to 3-4 cm at 3 kg m(-3) s(-1) perfusion. Differential power control to transducer elements and sectors demonstrates tailoring of heating along the device length and in angle. Sector cuts are associated with a 14-47 degrees acoustic dead zone, depending on cut width, resulting in a approximately 2-4 degrees C temperature reduction within the dead zone below Tmax. Dead zones can be oriented for thermal protection of the rectum and bladder. Fabricated devices have acoustic efficiencies of 33.4%-51.8% with acoustic output that is well collimated in length, reflects the sectoring strategy, and is strongly correlated with temperature distributions. A catheter-based ultrasound applicator was developed for endocervical implantation with locally targeted, 3-D conformal thermal delivery to the uterine cervix. Feasibility of heating clinically relevant target volumes was demonstrated with power control along the device length and in angle to treat the cervix with minimal thermal dose delivery to the rectum and bladder.
    Medical Physics 02/2011; 38(2):598-611. · 2.91 Impact Factor

Full-text (2 Sources)

Available from
May 31, 2014