Multimodality treatment for anaplastic thyroid carcinoma - Treatment outcome in 75 patients

Purpose

To retrospectively analyze the outcome of patients with anaplastic thyroid carcinoma (ATC) treated in the Erasmus MC.

Material and methods

Seventy-five ATC-patients were treated between 1972 and 2003. Mean age was 68 years. Tumor stage was IVA in 9%, IVB in 51%, and IVC in 40%. Thirty-six patients underwent up-front surgery, with 53% resulting in R0/R1 resection. Before 1988 adjuvant treatment consisted of conventional radiotherapy (RT) and/or chemotherapy (CT). As of 1988, 30 eligible patients were enrolled in a newly designed protocol. This consists of locoregional RT in 46 fractions of 1.1 Gy, given twice daily, followed by prophylactic irradiation of the lungs (PLI) in 5 daily fractions of 1.5 Gy. During radiation, low-dose Doxorubicine (15 mg/m²) is administered weekly and is followed by adjuvant Doxorubicine (50 mg/m²) 3-weekly up to a cumulative dose of 550 mg/m². Twenty-five ineligible patients were treated conventionally.

Results

Overall median survival was 3 months, 1-year OS 9%. Locoregional control was significantly higher in patients who had undergone R0/R1 resection or chemoradiation, with best results for patients who underwent both (complete remission in 89%). However, the survival benefit of patients who reached CR remained borderline (median OS 7 months, 1-year OS 32%). Three patients survived for more than 5 years; all had undergone R0/R1 surgical resection and chemoradiation. Acute toxicity in the protocol group was significantly higher than in the nonprotocol group, with 46% versus 11% grade 3 pharyngeal and/or esophageal toxicity.

Conclusion

Despite the ultimately dismal prognosis of ATC-patients, multimodality treatment significantly improved local control and improved the median survival.     

Feasibility of accelerated partial breast irradiation using three-dimensional conformal radiation therapy for Japanese women: a theoretical plan using six patients’ CT data

Background Several methods have been reported for accelerated partial breast irradiation (APBI), but in Japan, there are few facilities where brachytherapy or intra-operative radiotherapy is available. Japanese women have smaller physiques than American women in general. Thus, we developed external beam plans for APBI using computed tomography (CT) data of Japanese patients, to investigate whether APBI using three-dimensional conformal radiation therapy is safely applicable for Japanese women, while verifying the dose distributions. Methods We used CT data from six Japanese patients with early breast cancer, which were obtained in routine clinical practice during whole breast irradiation (WBI) after wide excision, and made 32 APBI plans according to the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-39 and the Radiation Therapy Oncology Group (RTOG) 0413 protocol, which compared APBI with WBI. We then investigated the compliance to the dose constraints of the protocol. Results None of 16 plans for the medial regions met the dose constraints regardless of laterality of the breast. The major reason was overdosage to the contralateral breast. Thirteen of 16 plans (81%) for the lateral regions met the dose constraints. The remaining three plans (19%) did not meet the dose limitation of the uninvolved normal breast, suggesting that a large ratio of the target to the breast was problematic. Conclusions In Japanese women, patients with a laterally located small tumor can be candidates for APBI using three-dimensional conformal radiation therapy.     

Current status of accelerated partial breast irradiation

Accelerated partial breast irradiation (APBI) is a radiotherapy method used in breast-conserving therapy. In APBI, the tumor bed is topically irradiated over a short period after breast-conserving surgery. The fundamental concept underlying APBI is that more than 70% of ipsilateral breast tumor recurrence occurs in the neighborhood of the original tumor, and that hypofractionated radiotherapy can be applied safely when the irradiated volume is small enough. It is expected to reduce the time and cost required for conventional whole breast irradiation while maintaining equivalent local control. Several techniques including multicatheter interstitial brachytherapy, intracavitary brachytherapy, intraoperative radiation therapy, and 3D conformal external beam radiation therapy have been proposed, and each of them has its own advantages and drawbacks. Although APBI is increasingly used in the United States and Europe, and the short-term results are promising, its equivalence with whole breast radiation therapy is not fully established. In addition, because the average breast size in Japan is considerably smaller than in the West world, the application of APBI to Japanese patients is technically more challenging. At this point, APBI is still an investigational treatment in Japan, and the optimal method of radiation delivery as well as its long-term efficacy and safety should be clarified in clinical trials.     

Comparison of target registration errors for multiple image-guided techniques in accelerated partial breast irradiation

PURPOSE: External beam accelerated partial breast irradiation requires accurate localization of the target volume for each treatment fraction. Using the concept of target registration error (TRE), the performance of several methods of target localization was compared. METHODS AND MATERIALS: Twelve patients who underwent external beam accelerated partial breast irradiation were included in this study. TRE was quantified for four methods of image guidance: standard laser-based setup, kilovoltage imaging of the chest wall, kilovoltage imaging of surgically implanted clips, and three-dimensional surface imaging of the breast. The use of a reference surface created from a free-breathing computed tomography scan and a reference surface directly captured with three-dimensional video imaging were compared. The effects of respiratory motion were also considered, and gating was used for 8 of 12 patients. RESULTS: The median value of the TRE for the laser, chest wall, and clip alignment was 7.1 mm (n=94), 5.4 mm (n=81), and 2.4 mm (n=93), respectively. The median TRE for gated surface imaging based on the first fraction reference surface was 3.2 mm (n=49), and the TRE for gated surface imaging using the computed tomography-based reference surface was 4.9 mm (n=56). The TRE for nongated surface imaging using the first fraction reference surface was 6.2 mm (n=25). CONCLUSIONS: The TRE of surface imaging using a reference surface directly captured with three-dimensional video and the TRE for clip-based setup were within 1 mm. Gated capture is important for surface imaging to reduce the effects of respiratory motion in accelerated partial breast irradiation.     

Intercalary segmental reconstruction after bone tumor resection

Background/aims

Intercalary resection can be used for primary as well as metastatic tumors. Reconstruction options include vascularized fibula graft, interposition of an allograft, combination of vascularized fibula and allograft, segmental prosthesis, insertion of an extracorporally irradiated autograft, segmental transportation, either with external fixation or by using an intramedullary rod, intercalary scaffolds augmented with growth factors, and technical refinements for the resection of tumors located close to the growth plate. The purpose of this review is to discuss the indications, limitations and pitfalls of each of these techniques.

Methods

The PubMed database was searched for articles on intercalary reconstruction after bone tumor resection and for the different reconstruction options presented in this review. Additionally, cross-referencing was used to cover articles eventually undetected by the respective search strategies. The resulting articles were then reviewed with regard to the different techniques, outcomes and complications of the reconstruction options.

Results

With the advance of imaging techniques and the use of chemotherapy for malignant bone tumors, surgical techniques can be refined. There are many techniques for the reconstruction of large intercalary defects of long bones, with which the orthopedic oncologist needs to be familiar. General oncologic principles of achieving a wide margin still need to be respected.

Conclusion

The techniques presented in this review will allow a better functional outcome of patients. It will continue to be important to carefully analyze each patient's situation and to adapt and individualize the method of reconstruction used.     

Combined effects of bevacizumab with erlotinib and irradiation: a preclinical study on a head and neck cancer orthotopic model

Clinical benefit has been demonstrated in patients with head and neck tumours receiving an anti-epidermal growth factor receptor (EGFR) agent in combination with radiotherapy (RT). Recent preclinical and clinical studies suggest beneficial effects from combining anti-angiogenic drugs with RT. To investigate the effect of combining these approaches, we evaluated in vivo the anti-tumour efficacy of the anti-angiogenic compound bevacizumab, a highly specific monoclonal antibody directed against the vascular endothelial growth factor (VEGF), erlotinib, an EGFR tyrosine kinase inhibitor, and irradiation given alone and in combination. Investigations were performed using a VEGF-secreting human head and neck tumour cell line, CAL33, with a high EGFR content, injected as orthotopic xenografts into the mouth floor of nude mice. Three days after tumour cell injection, bevacizumab (5 mg kg(-1), 5 days a week, i.p.), erlotinib (100 mg kg(-1), 5 days a week, orally) and irradiation (6 Gy, 3 days a week) were administered alone and in combination for 10 days. As compared with the control, concomitant administration of drugs produced a marked and significant supra-additive decrease in tumour mass; the addition of irradiation almost completely abolished tumour growth. The drug association markedly reduced the number of metastatic nodes and the triple combination significantly reduced the total number of pathologically positive lymph nodes as compared with controls. The RT-induced proliferation, reflected by Ki67 labelling, was reduced to control level with the triple combination. Radiotherapy induced a strong and very significant increase in tumour angiogenesis, which was no longer observed when combined with erlotinib and bevacizumab. The efficacy of the combination of bevacizumab+erlotinib and RT may be of clinical importance in the management of head and neck cancer patients.