IMRT in Hypopharyngeal Tumors

Background and Purpose:: Intensity-modulated radiation therapy (IMRT) data on hypopharyngeal cancer (HC) are scant. In this study, the authors report on early results in an own HC patient cohort treated with IMRT. A more favorable outcome as compared to historical data on conventional radiation techniques was expected. Patients and Methods:: 29 consecutive HC patients were treated with simultaneous integrated boost (SIB) IMRT between 01/2002 and 07/2005 (mean follow-up 16 months, range 4-44 months). Doses of 60-71 Gy with 2.0-2.2 Gy/fraction were applied. 26/29 patients were definitively irradiated, 86% received simultaneous cisplatin-based chemotherapy. 60% presented with locally advanced disease (T3/4 Nx, Tx N2c/3). Mean primary tumor volume measured 36.2 cm3 (4-170 cm3), mean nodal volume 16.6 cm3 (0-97 cm3). Results:: 2-year actuarial local, nodal, distant control, and overall disease-free survival were 90%, 93%, 93%, and 90%, respectively. In 2/4 patients with persistent disease (nodal in one, primary in three), salvage surgery was performed. The mean dose to the spinal cord (extension of > 5-15 mm) was 26 Gy (12-38 Gy); the mean maximum (point) dose was 44.4 Gy (26-58.9 Gy). One grade (G) 3 dysphagia and two G4 reactions (laryngeal fibrosis, dysphagia), both following the schedule with 2.2 Gy per fraction, have been observed so far. Larynx preservation was achieved in 25/26 of the definitively irradiated patients (one underwent a salvage laryngectomy); 23 had no or minimal dysphagia (G0-1). Conclusion:: Excellent early disease control and high patient satisfaction with swallowing function in HC following SIB IMRT were observed; these results need to be confirmed based on a longer follow-up period. In order to avoid G4 reactions, SIB doses of < 2.2 Gy/fraction are recommended for large tumors involving laryngeal structure

Prophylaxis of Heterotopic Ossification in Patients Sedated after Polytrauma: Medical and Ethical Considerations

Background and Purpose:: Heterotopic ossification (HO) often follows acetabular fractures after multitrauma. Irradiation is a mean for prophylaxis. We established a standard procedure in our hospital for patients under sedation, when obtaining informed consent for HO prophylaxis is impossible. Patients and Methods:: We reviewed current scientific evidence, calculated the risks of radiation and presented the ethical and legal framework. The subject was scrutinised by an interdisciplinary panel. Results:: Irradiation is the most effective means for prophylaxis and has few adverse effects in adult patients with fractures of the acetabulum. The lifetime risk of radiation-induced cancer or infertility are insignificant. Conclusions:: Informed consent for irradiation should be obtained before operation whenever possible. When this cannot be done prophylaxis can be postponed for a maximum of 3 days in order to obtain consent. If the patient is not able to communicate within this period, prophylactic irradiation should be given after consulting the relatives. The patient must be informed as soon as possibl

Local tumor control and toxicity in HIV-associated anal carcinoma treated with radiotherapy in the era of antiretroviral therapy

PURPOSE: To investigate the outcome of HIV-seropositive patients under highly active antiretroviral treatment (HAART) with anal cancer treated with radiotherapy (RT) alone or in combination with standard chemotherapy (CT). PATIENTS AND METHODS: Clinical outcome of 81 HIV-seronegative patients (1988 – 2003) and 10 consecutive HIV-seropositive patients under HAART (1997 – 2003) that were treated with 3-D conformal RT of 59.4 Gy and standard 5-fluorouracil and mitomycin-C were retrospectively analysed. 10 TNM-stage and age matched HIV-seronegative patients (1992 – 2003) were compared with the 10 HIV-seropositive patients. Pattern of care, local disease control (LC), overall survival (OS), cancer-specific survival (CSS), and toxicity were assessed. RESULTS: RT with or without CT resulted in complete response in 100 % of HIV-seropositive patients. LC was impaired compared to matched HIV-seronegative patients after a median follow-up of 44 months (p = 0.03). OS at 5 years was 70 % in HIV-seropositive patients receiving HAART and 69 % in the matched controls. Colostomy-free survival was 70 % (HIV+) and 100 % (matched HIV-) and 78 % (all HIV-). No HIV-seropositive patient received an interstitial brachytherapy boost compared to 42 % of all HIV-seronegative patients and adherence to chemotherapy seemed to be difficult in HIV-seropositive patients. Acute hematological toxicity reaching 50 % was high in HIV-seropositive patients receiving MMC compared with 0 % in matched HIV-seronegative patients (p = 0.05) or 12 % in all HIV-seronegative patients. The rate of long-term side effects was low in HIV-seropositive patients. CONCLUSION: Despite high response rates to organ preserving treatment with RT with or without CT, local tumor failure seems to be high in HIV-positive patients receiving HAART. HIV-seropositive patients are subject to treatment bias, being less likely treated with interstitial brachytherapy boost probably due to HIV-infection, and they are at risk to receive less chemotherapy

Total Body Irradiation (TBI) in Pediatric Patients: A Single-center Experience after 30 Years of Low-dose Rate Irradiation

Abstract : Purpose: : To retrospectively analyze patient characteristics, treatment, and treatment outcome of pediatric patients with hematologic diseases treated with total body irradiation (TBI) between 1978 and 2006. Patients and Methods: : 32 pediatric patients were referred to the Department of Radiation-Oncology at the University of Zurich for TBI. Records of regular follow-up of 28 patients were available for review. Patient characteristics as well as treatment outcome regarding local control and overall survival were assessed. A total of 18 patients suffered from acute lymphoblastic leukemia (ALL), 5 from acute and 2 from chronic myelogenous leukemia, 1 from non-Hodgkin lymphoma, and 2 from anaplastic anemia. The cohort consisted of 15 patients referred after first remission and 13 patients with relapsed leukemia. Mean follow-up was 34 months (2-196 months) with 15 patients alive at the time of last follow-up. Eight patients died of recurrent disease, 1 of graft vs. host reaction, 2 of sepsis, and 2 patients died of a secondary malignancy. Results: : The 5-year overall survival rate (OS) was 60%. Overall survival was significantly inferior in patients treated after relapse compared to those treated for newly diagnosed leukemia (24% versus 74%; p=0.004). At the time of last follow-up, 11 patients survived for more than 36 months following TBI. Late effects (RTOG ≥3) were pneumonitis in 1 patient, chronic bronchitis in 1 patient, cardiomyopathy in 2 patients, severe cataractogenesis in 1 patient (48 months after TBI with 10 Gy in a single dose) and secondary malignancies in 2 patients (36 and 190 months after TBI). Growth disturbances were observed in all patients treated prepubertally. In 2 patients with identical twins treated at ages 2 and 7, a loss of 8% in final height of the treated twin was observed. Conclusion: : As severe late sequelae after TBI, we observed 2 secondary malignancies in 11 patients who survived in excess of 36 months. However, long-term morbidity is moderate following treatment with the fractionated TBI at the low-dose rate that was generally used here. Conditioning for bone marrow transplantation without radiation is an attractive option, but is not sufficiently effective to completely replace TBI for the most common pediatric indication

Target Motion Variability and On-Line Positioning Accuracy during External-Beam Radiation Therapy of Prostate Cancer with an Endorectal Balloon Device

Purpose:: To prospectively define the setup error and the interfraction prostate localization accuracy of the planning target volume (PTV) in the presence of an endorectal balloon (ERB) device. Patients and Methods:: Weekly portal images (PIs) of 15 patients undergoing external-beam radiotherapy were analyzed. Displacements of the isocenter and the center of the ERB were measured. The setup and target motion variability were assessed with regard to the position variability of the ERB. Results:: The setup error was random and target motion variability was largest in the craniocaudal direction. The mean displacement of the isocenter was 2.1 mm (± 1.2 mm SD [standard deviation]), 2.4 mm (± 2.2 mm SD), and 3.8 mm (± 4.0 mm SD) in the left-right, craniocaudal, and anteroposterior directions, respectively (p = 0.1). The mean displacement of the ERB was 2.0 mm (± 1.4 mm SD), 4.1 mm (± 2.0 mm SD), and 3.8 mm (± 3.3 mm SD; p = 0.03). Setup margin and internal margin contributed equally to the PTV margin. Cumulative placement insecurity of the field and the ERB together was 4.0 mm (± 2.1 mm SD) laterally, 6.4 mm (± 2.5 mm SD) craniocaudally, and 7.7 mm (± 7.0 mm SD) anteroposteriorly. The 95% CIs (confidence intervals) were 2.9-5.2 mm, 5.1-7.8 mm, and 3.8-11.5 mm. In 35% of cases, the estimation of the dorsal margin exceeded 1 cm. Conclusion:: Margin estimate dorsally may exceed 1 cm and on-line position verification with an ERB cannot be recommended for dose escalation > 70 G

Osteoradionecrosis of the Mandible: Minimized Risk Profile Following Intensity-Modulated Radiation Therapy (IMRT)

Background and Purpose:: Osteoradionecrosis (ON) of the mandible is a serious late complication of high-dose radiation therapy for tumors of the oropharynx and oral cavity. After doses between 60 and 72 Gy using standard fractionation, an incidence of ON between 5% and 15% is reported in a review from 1989, whereas in more recent publications using moderately accelerated or hyperfractionated irradiation and doses between 69 and 81 Gy, the incidence of ON is between 60 Gy for oropharyngeal or oral cavity cancer). 21/73 patients were treated in a postoperative setting, 52 patients underwent primary definitive irradiation. In 56 patients concomitant cisplatin-based chemotherapy was applied. Mean follow-up time was 22 months (12-46 months). Oral cavity including the mandible bone outside the planning target volume was contoured and dose-volume constraints were defined in order to spare bone tissue. Dose-volume histograms were obtained from contoured mandible in each patient and were analyzed and related to clinical mandible bone tolerance. Results:: Using IMRT with doses between 60 and 75 Gy (mean 67 Gy), on average 7.8, 4.8, 0.9, and 0.3 cm3 were exposed to doses > 60, 65, 70, and 75 Gy, respectively. These values are substantially lower than when using three-dimensional conformal radiotherapy. The difference has been approximately quantified by comparison with a historic series. Additional ON risk factors of the patients were also analyzed. Only one grade 3 ON of the lingual horizontal branch, treated with lingual decortication, was observed. Conclusion:: Using IMRT, only very small partial volumes of the mandibular bone are exposed to high radiation doses. This is expected to translate into a further reduction of ON and improved osseointegration of dental implant

PET/CT Staging Followed by Intensity-Modulated Radiotherapy (IMRT) Improves Treatment Outcome of Locally Advanced Pharyngeal Carcinoma: a matched-pair comparison

BACKGROUND: Impact of non-pharmacological innovations on cancer cure rates is difficult to assess. It remains unclear, whether outcome improves with 2- [18-F]-fluoro-2-deoxyglucose-positron emission tomography and integrated computer tomography (PET/CT) and intensity-modulated radiotherapy (IMRT) for curative treatment of advanced pharyngeal carcinoma. PATIENTS AND METHODS: Forty five patients with stage IVA oro- or hypopharyngeal carcinoma were staged with an integrated PET/CT and treated with definitive chemoradiation with IMRT from 2002 until 2005. To estimate the impact of PET/CT with IMRT on outcome, a case-control analysis on all patients with PET/CT and IMRT was done after matching with eighty six patients treated between 1991 and 2001 without PET/CT and 3D-conformal radiotherapy with respect to gender, age, stage, grade, and tumor location with a ratio of 1:2. Median follow-up was eighteen months (range, 6-49 months) for the PET/CT-IMRT group and twenty eight months (range, 1-168 months) for the controls. RESULTS: PET/CT and treatment with IMRT improved cure rates compared to patients without PET/CT and IMRT. Overall survival of patients with PET/CT and IMRT was 97% and 91% at 1 and 2 years respectively, compared to 74% and 54% for patients without PET/CT or IMRT (p = 0.002). The event-free survival rate of PET/CT-IMRT group was 90% and 80% at 1 and 2 years respectively, compared to 72% and 56% in the control group (p = 0.005). CONCLUSION: PET/CT in combination with IMRT and chemotherapy for pharyngeal carcinoma improve oncological therapy of pharyngeal carcinomas. Long-term follow-up is needed to confirm these findings

Chemo-radiation with or without mandatory split in anal carcinoma: experiences of two institutions and review of the literature

BACKGROUND: The split-course schedule of chemo-radiation for anal cancer is controversial. METHODS: Eighty-four patients with invasive anal cancer treated with definitive external beam radiotherapy (RT) with a mandatory split of 12 days (52 patients, Montreal, Canada) or without an intended split (32 patients, Zurich, Switzerland) were reviewed. Total RT doses were 52 Gy (Montreal) or 59.4 Gy (Zurich) given concurrently with 5-FU/MMC. RESULTS: After a mean follow-up of 40 +/- 27 months, overall survival and local tumor control at 5 years were 57% and 78% (Zurich) compared to 67% and 82% (Montreal), respectively. Split duration of patients with or without local relapse was 15 +/- 7 d vs. 14 +/- 7 d (Montreal, NS) and 11 +/- 11 d vs. 5 +/- 7 d (Zurich; P or = 7 d) had impaired cancer-specific survival compared with patients with only minor interruption (<7 d) (P = 0.06). Bowel toxicity was associated with prolonged RT (P = 0.03) duration as well as increased relapse probability (P = 0.05). Skin toxicity correlated with institution and was found in 79% (Montreal) and 28% (Zurich) (P < 0.0001). CONCLUSIONS: The study design did not allow demonstrating a clear difference in efficacy between the treatment regimens with or without short mandatory split. Cause-specific outcome appears to be impaired by unplanned prolonged interruption

IMRT in Hypopharyngeal Tumors

Background and Purpose:: Intensity-modulated radiation therapy (IMRT) data on hypopharyngeal cancer (HC) are scant. In this study, the authors report on early results in an own HC patient cohort treated with IMRT. A more favorable outcome as compared to historical data on conventional radiation techniques was expected. Patients and Methods:: 29 consecutive HC patients were treated with simultaneous integrated boost (SIB) IMRT between 01/2002 and 07/2005 (mean follow-up 16 months, range 4-44 months). Doses of 60-71 Gy with 2.0-2.2 Gy/fraction were applied. 26/29 patients were definitively irradiated, 86% received simultaneous cisplatin-based chemotherapy. 60% presented with locally advanced disease (T3/4 Nx, Tx N2c/3). Mean primary tumor volume measured 36.2 cm3 (4-170 cm3), mean nodal volume 16.6 cm3 (0-97 cm3). Results:: 2-year actuarial local, nodal, distant control, and overall disease-free survival were 90%, 93%, 93%, and 90%, respectively. In 2/4 patients with persistent disease (nodal in one, primary in three), salvage surgery was performed. The mean dose to the spinal cord (extension of > 5-15 mm) was 26 Gy (12-38 Gy); the mean maximum (point) dose was 44.4 Gy (26-58.9 Gy). One grade (G) 3 dysphagia and two G4 reactions (laryngeal fibrosis, dysphagia), both following the schedule with 2.2 Gy per fraction, have been observed so far. Larynx preservation was achieved in 25/26 of the definitively irradiated patients (one underwent a salvage laryngectomy); 23 had no or minimal dysphagia (G0-1). Conclusion:: Excellent early disease control and high patient satisfaction with swallowing function in HC following SIB IMRT were observed; these results need to be confirmed based on a longer follow-up period. In order to avoid G4 reactions, SIB doses of < 2.2 Gy/fraction are recommended for large tumors involving laryngeal structure