Intensity-modulated radiotherapy for resected mesothelioma: the Duke experience

PURPOSE: To assess the safety and efficacy of intensity-modulated radiotherapy (IMRT) after extrapleural pneumonectomy for malignant pleural mesothelioma. METHODS AND MATERIALS: Thirteen patients underwent IMRT after extrapleural pneumonectomy between July 2005 and February 2007 at Duke University Medical Center. The clinical target volume was defined as the entire ipsilateral hemithorax, chest wall incisions, including drain sites, and involved nodal stations. The dose prescribed to the planning target volume was 40-55 Gy (median, 45). Toxicity was graded using the modified Common Toxicity Criteria, and the lung dosimetric parameters from the subgroups with and without pneumonitis were compared. Local control and survival were assessed. RESULTS: The median follow-up after IMRT was 9.5 months. Of the 13 patients, 3 (23%) developed Grade 2 or greater acute pulmonary toxicity (during or within 30 days of IMRT). The median dosimetric parameters for those with and without symptomatic pneumonitis were a mean lung dose (MLD) of 7.9 vs. 7.5 Gy (p = 0.40), percentage of lung volume receiving 20 Gy (V(20)) of 0.2% vs. 2.3% (p = 0.51), and percentage of lung volume receiving 5 Gy (V(20)) of 92% vs. 66% (p = 0.36). One patient died of fatal pulmonary toxicity. This patient received a greater MLD (11.4 vs. 7.6 Gy) and had a greater V(20) (6.9% vs. 1.9%), and V(5) (92% vs. 66%) compared with the median of those without fatal pulmonary toxicity. Local and/or distant failure occurred in 6 patients (46%), and 6 patients (46%) were alive without evidence of recurrence at last follow-up. CONCLUSIONS: With limited follow-up, 45-Gy IMRT provides reasonable local control for mesothelioma after extrapleural pneumonectomy. However, treatment-related pulmonary toxicity remains a significant concern. Care should be taken to minimize the dose to the remaining lung to achieve an acceptable therapeutic ratio.     

Intensity-modulated radiotherapy for head-and-neck rhabdomyosarcoma

PURPOSE: To determine the preliminary results of intensity-modulated radiotherapy (IMRT) for head-and-neck rhabdomyosarcoma. METHODS AND MATERIALS: Twenty-eight patients underwent IMRT as a part of multimodality therapy. Twenty-one tumors were parameningeal, three were orbital, and four were in other sites. The median age was 8 years (range, 1-29 years). Most (89%) had Group III disease. Intracranial extension was present in 71% of parameningeal tumors. A 1.5-cm margin was used, and the median dose was 50.4 Gy (range, 30-55.8 Gy). RESULTS: The actuarial 3-year survival rate for patients with parameningeal tumors was 65%. The 3-year actuarial freedom from failure rate was 95% locally, 90% in regional nodes, 88% in the central nervous system, and 80% at distant sites. No failures occurred among patients with orbit tumors; a single central nervous system failure occurred in 1 patient with a lip/cheek tumor. Disease-free survival was significantly worse for patients with alveolar histologic features (p = 0.01). Acute radiation toxicity was similar to that reported by the Intergroup Rhabdomyosarcoma Study Group. Late radiation toxicity was recorded and was mild. CONCLUSION: IMRT with image fusion results in outstanding local control despite the use of a reduced margin. However, survival among patients with alveolar histologic findings or intracranial extension remains unacceptably low.     

Intensity-modulated radiotherapy with concurrent chemotherapy for previously irradiated, recurrent head and neck cancer

PURPOSE: Primary treatment fails in >70% of locally advanced head and neck cancer patients. Salvage therapy has a 30-40% response rate, but few long-term survivors. Intensity-modulated radiotherapy (IMRT) has recently emerged as a new modality for salvage therapy. This retrospective study evaluated our experience using every-other-week IMRT with concurrent chemotherapy. METHODS AND MATERIALS: Between 2001 and 2006, 41 patients underwent IMRT as repeat RT with concurrent chemotherapy. All but 6 patients received 60 Gy at 2 Gy/fraction. RT was delivered on an alternating week schedule. RESULTS: With a median follow-up time of 14 months, the overall response rate was 75.6%, with a complete response and partial response rate of 58.5% and 17.1%, respectively. The Kaplan-Meier estimate of overall survival, disease-free survival, and progression-free survival at 24 months was 48.7%, 48.1%, and 38%, respectively. Patients who underwent surgery as a part of their salvage therapy had a mean estimated survival of 30.9 months compared with 22.8 months for patients who received only chemoradiotherapy (p = 0.126). Grade 3 or 4 acute toxicities occurred in 31.7% of patients, but all had resolved within 2 months of therapy completion. No deaths occurred during treatment, except for 1 patient, who died shortly after discontinuing treatment early because of previously undiagnosed metastatic disease; 6 patients had long-term complications. CONCLUSIONS: Concurrent chemotherapy with repeat radiotherapy with IMRT given every other week appears to be both well tolerated and feasible in patients treated with previous radiotherapy for recurrent head and neck cancer. IMRT represents a reasonable modality for reducing treatment-related toxicities in a repeat RT setting.     

Intensity-modulated radiotherapy for head and neck cancer of unknown primary: toxicity and preliminary efficacy

PURPOSE: Unknown primary head and neck cancers often require comprehensive mucosal and bilateral neck irradiation. With conventional techniques, significant toxicity can develop. Intensity-modulated radiotherapy (IMRT) has the potential to minimize the toxicity. METHODS AND MATERIALS: Between 2000 and 2005, 21 patients underwent IMRT for unknown primary head and neck cancer at our center. Of the 21 patients, 5 received IMRT with definitive intent and 16 as postoperative therapy; 14 received concurrent chemotherapy and 7 IMRT alone. The target volumes included the bilateral neck and mucosal surface. The median dose was 66 Gy. Acute and chronic toxicities, esophageal strictures, and percutaneous endoscopic gastrostomy tube dependence were evaluated. Progression-free survival, regional progression-free survival, distant metastasis-free survival, and overall survival were estimated with Kaplan-Meier curves. RESULTS: With a median follow-up of 24 months, the 2-year regional progression-free survival, distant metastasis-free survival, and overall survival rate was 90%, 90%, and 85%, respectively. Acute grade 1 and 2 xerostomia was seen in 57% and 43% of patients, respectively. Salivary function improved with time. Percutaneous endoscopic gastrostomy tube placement was required in 72% with combined modality treatment and 43% with IMRT alone. Only 1 patient required percutaneous endoscopic gastrostomy support at the last follow-up visit. Two patients treated with combined modality and one treated with IMRT alone developed esophageal strictures, but all had improvement or resolution with dilation. CONCLUSION: The preliminary analysis of IMRT for unknown primary head and neck cancer has shown acceptable toxicity and encouraging efficacy. The analysis of the dosimetric variables showed excellent tumor coverage and acceptable doses to critical normal structures. Esophageal strictures developed but were effectively treated with dilation. Techniques to limit the esophageal dose could help further minimize this complication.     

Intensity-modulated radiotherapy significantly reduces xerostomia compared with conventional radiotherapy

PURPOSE: Xerostomia is a severe complication after radiotherapy for oropharyngeal cancer, as the salivary glands are in close proximity with the primary tumor. Intensity-modulated radiotherapy (IMRT) offers theoretical advantages for normal tissue sparing. A Phase II study was conducted to determine the value of IMRT for salivary output preservation compared with conventional radiotherapy (CRT). METHODS AND MATERIALS: A total of 56 patients with oropharyngeal cancer were prospectively evaluated. Of these, 30 patients were treated with IMRT and 26 with CRT. Stimulated parotid salivary flow was measured before, 6 weeks, and 6 months after treatment. A complication was defined as a stimulated parotid flow rate <25% of the preradiotherapy flow rate. RESULTS: The mean dose to the parotid glands was 48.1 Gy (SD 14 Gy) for CRT and 33.7 Gy (SD 10 Gy) for IMRT (p < 0.005). The mean parotid flow ratio 6 weeks and 6 months after treatment was respectively 41% and 64% for IMRT and respectively 11% and 18% for CRT. As a result, 6 weeks after treatment, the number of parotid flow complications was significantly lower after IMRT (55%) than after CRT (87%) (p = 0.002). The number of complications 6 months after treatment was 56% for IMRT and 81% for CRT (p = 0.04). CONCLUSIONS: IMRT significantly reduces the number of parotid flow complications for patients with oropharyngeal cancer.     

Intensity-modulated radiotherapy prolongs the survival of patients with nasopharyngeal carcinoma compared with conventional two-dimensional radiotherapy: A 10-year experience with a large cohort and long follow-up

BackgroundTo evaluate the survival benefit of intensity-modulated radiotherapy (IMRT) compared with conventional two-dimensional radiotherapy (2D-CRT) in nasopharyngeal carcinoma (NPC) using a large cohort with long follow-up.MethodsWe retrospectively analysed 7081 non-metastatic NPC patients who received curative IMRT or 2D-CRT from February 2002 to December 2011.ResultsOf the 7081 patients, 2245 (31.7%) were administered IMRT, while 4836 (68.3%) were administered 2D-CRT. At 5 years, the patients administered IMRT had significantly higher local relapse-free survival (LRFS), loco-regional relapse-free survival (LRRFS), progression-free survival (PFS) and overall survival (OS) (95.6%, 92.5%, 82.1% and 87.4%, respectively) than those administered 2D-CRT (90.8%, 88.5%, 76.7% and 84.5%, respectively; p < 0.001). The distant metastasis-free survival (DMFS) was higher for IMRT than 2D-CRT, with borderline significance (87.6% and 85.7%, respectively; p = 0.056). However, no difference was observed between IMRT and 2D-CRT in nodal relapse-free survival (NRFS; 96.3% and 97.4%, respectively; p = 0.217). Multivariate analyses showed that IMRT was an independent protective prognostic factor for LRFS, LRRFS and PFS, but not NRFS, DMFS or OS.ConclusionsIMRT provided an improved LRFS, LRRFS and PFS in both the early and advanced T classifications and overall stage for non-disseminated NPC compared with 2D-CRT. However, no significant advantage was observed in NRFS, DMFS or OS when IMRT was used.     

Intensity-modulated radiotherapy for nasopharyngeal carcinoma: clinical correlation of dose to the pharyngo-esophageal axis and dysphagia

PURPOSE: The aim of this study was to quantify the dose delivered to the pharyngo-esophageal axis using different intensity-modulated radiation therapy (IMRT) techniques for treatment of nasopharyngeal carcinoma and to correlate this with acute swallowing toxicity. METHODS AND MATERIALS: The study population consisted of 28 patients treated with IMRT between February 2002 and August 2005: 20 with whole field IMRT (WF-IMRT) and 8 with IMRT fields junctioned with an anterior neck field with central shielding (j-IMRT). Dose to the pharyngo-esophageal axis was measured using dose-volume histograms. Acute swallowing toxicity was assessed by review of dysphagia grade during treatment and enteral feeding requirements. RESULTS: The mean pharyngo-esophageal dose was 55.2 Gy in the WF-IMRT group and 27.2 Gy in the j-IMRT group, p < 0.001. Ninety-five percent (19/20) of the WF-IMRT group developed Grade 3 dysphagia compared with 62.5% (5/8) of the j-IMRT group, p = 0.06. Feeding tube duration was a median of 38 days for the WF-IMRT group compared with 6 days for the j-IMRT group, p = 0.04. CONCLUSIONS: Clinical vigilance must be maintained when introducing new technology to ensure that unanticipated adverse effects do not result. Although newer planning systems can reduce the dose to the pharyngo-esophageal axis with WF-IMRT, the j-IMRT technique is preferred at least in patients with no gross disease in the lower neck.     

MR引导放疗在胰腺癌中的应用

放疗是治疗胰腺癌的重要手段。但受胰腺运动等因素影响,放疗疗效难以充分发挥。更高效的胰腺癌放疗有赖于运动管理方式的改进与高质量的图像引导。新兴的MR引导放疗技术软组织分辨率高、无额外辐射、能进行功能成像,经过大量研究评估与验证,其在靶区与危及器官的精准勾画、辅助运动管理和自适应放疗等方面有着巨大优势,有望更好地发挥放疗在...     

调强放疗对鼻咽癌患者甲状腺功能的影响

目的 探讨鼻咽癌患者调强放射治疗后早期甲状腺功能的变化情况,为甲状腺功能保护提供依据.方法 收集经病理证实、排除基础甲状腺疾病且接受IMRT治疗的鼻咽癌患者.分析对比放疗前后TT3和TT4水平.结果 全组患者治疗前、后TT3水平分别为1.83 IU/L、1.69 IU/L,治疗前、后TT4水平分别为124.66 IU/L、127.23 IU/L.其中150例(59.8％)治疗后TT3水平下降,变化具有统计学差异(P=0.001).N3患者放疗后血清TT3及TT4水平均明显降低(P值分别为0.043、0.032).结论 IMRT模式下,鼻咽癌患者放疗结束时甲状腺激素降低,N3患者尤为明显.N3患者可运用VMAT/Tomotherapy等技术降低甲状腺照射剂量,且应早期监测甲状腺激素水平,发现问题及早干预.     

Intensity-modulated radiation therapy (IMRT) for meningioma

To assess the safety and efficacy of intensity-modulated radiation therapy (IMRT) in the treatment of intracranial meningioma.

Forty patients with intracranial meningioma (excluding optic nerve sheath meningiomas) were treated using IMRT with the NOMOS Peacock system between 1994 and 1999. Twenty-five patients received IMRT after surgery either as adjuvant therapy for incomplete resection or for recurrence, and 15 patients received definitive IMRT after presumptive diagnosis based on imaging. Thirty-two patients had skull base lesions, and 8 had nonskull base lesions. The prescribed dose ranged from 40 to 56 Gy (median 50.4 Gy) at 1.71 to 2 Gy per fraction, and the volume of the primary target ranged from 1.55 to 324.57 cc (median 20.22 cc). The mean dose to the target ranged from 44 to 60 Gy (median 53 Gy). Follow-up ranged from 6 to 71 months (median 30 months). Acute and chronic toxicity were assessed using Radiation Therapy Oncology Group (RTOG) morbidity criteria and tumor response was assessed by patient report, examination, and imaging. Overall survival, progression-free survival, and local control were calculated using the Kaplan-Meier method.

Cumulative 5-year local control, progression-free survival, and overall survival were 93%, 88%, and 89%, respectively. Two patients progressed after IMRT, one locally and one distantly. Each was treated with IMRT after multiple recurrences of benign meningioma over many years. Both were found to have malignant meningioma at the time of relapse after IMRT, and it is likely their tumors had already undergone malignant change by the time IMRT was given. Defined normal structures generally received a significantly lower dose than the target. The most common acute central nervous system (CNS) toxicity was mild headache, usually relieved with steroids. One patient experienced RTOG Grade 3 acute CNS toxicity, and 2 experienced Grade 3 or higher late CNS toxicity, with one possible treatment-related death. No toxicity was observed with mean doses to the optic nerve/chiasm up to 47 Gy and maximum doses up to 55 Gy.

IMRT is a promising new technology that is safe and efficacious in the primary and adjuvant treatment of intracranial meningiomas. A history of local aggression may indicate malignant degeneration and predict a poorer outcome. Toxicity data are encouraging, but the potential for serious side effects exists, as demonstrated by one possible treatment-related death. Larger cohort and longer follow-up are needed to better define efficacy and late toxicity of IMRT.