Smart (simultaneous modulated accelerated radiation therapy) boost: a new accelerated fractionation schedule for the treatment of head and neck cancer with intensity modulated radiotherapy.

PURPOSE: To report the initial experience in the definitive treatment of head and neck carcinomas using SMART (Simultaneous Modulated Accelerated Radiation Therapy) boost technique. Radiation was delivered via IMRT (Intensity Modulated Radiotherapy). The following parameters were evaluated: acute toxicity, initial tumor response, clinical feasibility, dosimetry and cost. METHODS AND MATERIALS: Between January 1996 and December 1997, 20 patients with primary head and neck carcinomas were treated with SMART boost technique. The treatment fields encompassed two simultaneous targets. The primary target included palpable and visible disease sites. The secondary target included regions at risk for microscopic disease. Daily fractions of 2.4 Gy and 2 Gy were prescribed and delivered to the primary and secondary targets to a total dose of 60 Gy and 50 Gy, respectively. Lower neck nodes were treated with a single conventional anterior portal. This fractionation schedule was completed in 5 weeks with 5 daily fractions weekly. Toxicity was evaluated by RTOG acute toxicity grading criteria, evidence of infection at immobilization screw sites, subjective salivary function, weight loss, and the need for treatment split. Mean follow-up was 15.2 months. Initial tumor response was assessed by clinical and radiographical examinations. Clinical feasibility was evaluated by the criteria: time to treat patient, immobilization, and treatment planning and QA time. In dosimetry, we evaluated the mean doses of both targets and normal tissues and percent targets' volume below goal. To evaluate cost, Medicare allowable charge for SMART boost was compared to those of conventional fractionated and accelerated radiotherapy. RESULTS: ACUTE TOXICITY: None of the patients had a screw site infection and all patients healed well after completion of radiotherapy. Sixteen of 20 patients (80%) completed the treatment within 40 days without any split. Sixteen patients (80%) had RTOG Grade 3 mucositis while 10 patients (50%) had Grade 3 pharyngitis. Three of 20 patients (15%) had weight loss greater than 10% of their pretreatment weight. Ten patients (50%) required intravenous fluids, tube feeding or both. Nine patients (45%) reported moderate xerostomia with significant relief reported within 6 months. INITIAL TUMOR RESPONSE: 19 patients (95 %) had complete response (CR) while one had partial response (PR). The patient with PR had stable disease on imaging at 12 months follow-up. Two patients were found to have lung metastases at 2 months and 5 months follow-up. To date, there have been two local recurrences in the complete responders. Both patients had nasopharyngeal primary; one was retreated with radioactive Cesium-137 implant and the other died from the disease. CLINICAL FEASIBILITY: The average treatment time for a three-arc treatment was 17.5 minutes and 2.5 minutes for each additional arc. Eleven patients (55%) had four-arc treatment while six patients (30%) had five-arc treatment and three patients (15%) had three-arc treatment. Immobilization was reproducible within less than 2 mm. The treatment planning, QA and documentation prior to treatment averaged 2 days. DOSIMETRY: The mean doses to the primary and secondary targets were 64.4 Gy and 54.4 Gy, respectively; 8.9% of the primary target volume and 11.6% of the secondary target volume were below prescribed dose goal. The mean dose delivered to the mandible was 30 Gy, spinal cord 17 Gy, ipsilateral parotid 23 Gy, and contralateral parotid 21 Gy. COST: Total Medicare allowable charge for SMART boost was $7000 compared to $8600 (conventional) and $9400 (accelerated fractionation). CONCLUSIONS: SMART boost technique is an accelerated radiotherapy scheme that can be delivered with acceptable toxicity. It allows parotid sparing as evidenced both clinically and by dosimetry. Initial tumor response has been encouraging. It is clinically feasible and cost saving. A larger population of patients and a long-term fol     

Intensity-modulated radiotherapy in the treatment of nasopharyngeal carcinoma: an update of the UCSF experience

PURPOSE: To update our experience with intensity-modulated radiotherapy (IMRT) in the treatment of nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: Between April 1995 and October 2000, 67 patients underwent IMRT for NPC at the University of California-San Francisco (UCSF). There were 20 females and 47 males, with a mean age of 49 (range 17-82). The disease was Stage I in 8 (12%), Stage II in 12 (18%), Stage III in 22 (33%), and Stage IV in 25 (37%). IMRT was delivered using three different techniques: 1) manually cut partial transmission blocks, 2) computer-controlled auto-sequencing segmental multileaf collimator (SMLC), and 3) sequential tomotherapy using a dynamic multivane intensity modulating collimator (MIMiC). Fifty patients received concomitant cisplatinum and adjuvant cisplatinum and 5-FU chemotherapy according to the Intergroup 0099 trial. Twenty-six patients had fractionated high-dose-rate intracavitary brachytherapy boost and 1 patient had gamma knife radiosurgery boost after external beam radiotherapy.The prescribed dose was 65-70 Gy to the gross tumor volume (GTV) and positive neck nodes, 60 Gy to the clinical target volume (CTV), 50-60 Gy to the clinically negative neck, and 5-7 Gy in 2 fractions for the intracavitary brachytherapy boost. Acute and late normal tissue effects were graded according to the Radiation Therapy Oncology Group (RTOG) radiation morbidity scoring criteria. The local progression-free, local-regional progression-free, distant metastasis-free rates, and the overall survival were calculated using the Kaplan-Meier method. RESULTS: With a median follow-up of 31 months (range 7 to 72 months), there has been one local recurrence at the primary site. One patient failed in the neck. Seventeen patients developed distant metastases; 5 of these patients have died. The 4-year estimates of local progression-free, local-regional progression-free, and distant metastases-free rates were 97%, 98%, and 66% respectively. The 4-year estimate of overall survival was 88%. The worst acute toxicity documented was as follows: Grade 1 or 2 in 51 patients, Grade 3 in 15 patients, and Grade 4 in 1 patient. The worst late toxicity was Grade 1 in 20 patients, Grade 2 in 15 patients, Grade 3 in 7 patients, and Grade 4 in 1 patient. At 3 months after IMRT, 64% of the patients had Grade 2, 28% had Grade 1, and 8% had Grade 0 xerostomia. Xerostomia decreased with time. At 24 months, only one of the 41 evaluable patients had Grade 2, 32% had Grade 1, and 66% had Grade 0 or no xerostomia. Analysis of the dose-volume histograms (DVHs) showed that the average maximum, mean, and minimum dose delivered were 79.3 Gy, 74.5 Gy, and 49.4 Gy to the GTV, and 78.9 Gy, 68.7 Gy, and 36.8 Gy to the CTV. An average of only 3% of the GTV and 3% of the CTV received less than 95% of the prescribed dose. CONCLUSION: Excellent local-regional control for NPC was achieved with IMRT. IMRT provided excellent tumor target coverage and allowed the delivery of a high dose to the target with significant sparing of the salivary glands and other nearby critical normal tissues.     

Local control, survival, and late toxicities of locally advanced nasopharyngeal carcinoma treated by simultaneous modulated accelerated radiotherapy combined with cisplatin concurrent chemotherapy: long-term results of a phase 2 study

BACKGROUND:

The aim of this phase 2 study was to determine the long‐term local control, survival, and late toxicities among patients with locally advanced nasopharyngeal carcinoma (NPC) treated with intensity‐modulated radiotherapy (IMRT) with the simultaneous modulated accelerated radiation therapy (SMART) boost technique and concurrent chemotherapy.

METHODS:

Eighty‐one patients with pathologically diagnosed locally advanced NPC were enrolled in this study. IMRT was delivered with the SMART boost technique at prescribed doses of 68 grays (Gy)/30 fraction to the nasopharynx gross target volume. Concurrent cisplatin chemotherapy (80 mg/m²/d on Days 1 and 22) was administered.

RESULTS:

The mean actual physical dose delivered to the nasopharynx gross target volume was 73.8 Gy, and the mean biologically effective dose (BED) for the nasopharynx gross target volume was 84.8 Gy. With a median follow‐up of 54 months, 4 (4.9%) patients experienced local recurrence. The 5‐year local control rate was 94.9%. Eighteen patients died. Among them, 66.7% died of distant metastasis. The 5‐year disease‐free and overall survivals were 76.7% and 74.5%, respectively. The most common late toxicities among 68 patients with ≥4 years follow‐up were grade 1‐2 xerostomia, hearing loss, skin dystrophy, and subcutaneous fibrosis. No grade 4 late toxicities were noted.

CONCLUSIONS:

IMRT with SMART to enhance BED and concurrent chemotherapy is feasible in patients with locally advanced NPC. Long‐term results showed excellent local control with fewer late toxicities, although no further improvement was noted in overall survival, and the major cause of death was distant metastasis. Exploration of more effective combined chemoradiation strategies is warranted. Cancer 2011. © 2010 American Cancer Society.     

Treatment of nasopharyngeal carcinoma with intensity-modulated radiotherapy: the Hong Kong experience

PURPOSE: To evaluate the efficacy of using intensity-modulated radiotherapy (IMRT) in the primary treatment of nasopharyngeal carcinoma (NPC), including the role of dose escalation above 66 Gy level. METHODS AND MATERIALS: Between July 2000 and September 2002, 63 newly diagnosed NPC patients were treated with IMRT. The disease was Stage I in 9 (14%), Stage II in 18 (29%), Stage III in 22 (35%), and Stage IV in 14 (22%). The prescribed dose was 66 Gy to the gross tumor volume (GTV) and positive neck nodes, 60 Gy to the planning target volume (PTV), and 54-60 Gy to the clinically negative neck. All 20 (100%) patients with T1-2a tumors received intracavitary brachytherapy (ICB) boost, and 15/42 (36%) patients with T2b-T4 tumors received conformal boost (8 Gy/4 fractions). Nineteen patients with advanced stage disease also received either neoadjuvant or concurrent chemotherapy. Acute and late normal tissue effects were graded according to the Radiation Therapy Oncology Group (RTOG) radiation morbidity scoring criteria. Local relapse-free survival (LRFS), nodal relapse-free survival (NRFS), distant metastasis-free survival (DMFS), and overall survival (OS) were estimated using the Kaplan-Meier method. RESULTS: With a median follow-up of 29 months (range 8-45 months), 4 patients developed local in-field failure, 1 patient developed regional relapse, and 13 patients developed distant metastases. All 4 patients with local failure had either T3 or T4 disease before primary treatment and did not have ICB or conformal boost. The 3-year actuarial LRFS, NRFS, DMFS, and OS were 92%, 98%, 79%, and 90%, respectively. Multivariate analysis showed that dose escalation above 66 Gy was significantly associated with better PFS and DMFS, whereas GTV size was a significant adverse factor for OS. The worst acute mucositis was Grade 1 or 2 in 36 (59%), and Grade 3 in 25 (41%) patients. Acute dysphagia requiring tube feeding occurred in 5 (8%) patients. The proportion of patients with Grade 2-3 xerostomia was 57% at 3 months, and 23% at 2 years after IMRT. Within the subset of patients with a mean parotid dose of <31 Gy, the proportions with Grade 2-3 xerostomia were 30% and 17% at 3 months and 2 years, respectively. CONCLUSION: Our experience of using IMRT in the primary treatment of NPC showed a very high rate of locoregional control and favorable toxicity profile. Furthermore, we found that dose escalation above 66 Gy of IMRT-based therapy was a significant determinant of progression-free survival and distant metastasis-free survival for advanced T-stage tumors. Distant metastases represent the predominant mode of treatment failure.     

Is there a “mucosa-sparing” benefit of IMRT for head-and-neck cancer?

PURPOSE: To investigate whether intensity-modulated radiation therapy (IMRT) allows more mucosal sparing than standard three-field technique (3FT) radiotherapy for early oropharyngeal cancer. METHODS AND MATERIALS: Whole-field IMRT plans were generated for 5 patients with early-stage oropharyngeal cancer according to Radiation Therapy Oncology Group 0022 (66 Gy/30 fractions/6 weeks) guidelines with and without a dose objective on the portion of mucosa not overlapping any PTV. 3FT plans were also generated for the same 5 patients with two fractionation schedules: conventional fractionation (CF) to 70 Gy/35 fractions/7 weeks and concomitant boost (CB) to 72 Gy/40 fractions/6 weeks. Cumulative dose volume histograms (DVHs) of the overall mucosal volume (as per in-house definition) from all trials were compared after transformation into the linear quadratic equivalent dose at 2 Gy per fraction with a time factor correction. RESULTS: Compared with IMRT without dose objective on the mucosa, a 30-Gy maximum dose objective on the mucosa allows approximately 20% and approximately 12% mean absolute reduction in the percentage of mucosa volume exposed to a dose equivalent to 30 Gy (p < 0.01) and 70 Gy (p < 0.01) at 2 Gy in 3 and 7 weeks, respectively, without detrimental effect on the coverage of other regions of interest. Without mucosal dose objective, IMRT is associated with a larger amount of mucosa exposed to clinically relevant doses compared with both concomitant boost and conventional fractionation; however, if a dose objective is placed, the reverse is true, with up to approximately 30% reduction in the volume of the mucosa in the high-dose region compared with both concomitant boost and conventional fractionation (p < 0.01). CONCLUSIONS: Intensity-modulated radiation therapy can be potentially provide more mucosal sparing than traditional approaches.     

Intensity-modulated radiation therapy for the treatment of nonanaplastic thyroid cancer

PURPOSE: Intensity-modulated radiation therapy (IMRT) enables highly conformal treatment for thyroid cancer (TC). In this study, we review outcomes/toxicity in a series of TC patients treated with IMRT. METHODS AND MATERIALS: Between July 2001 and January 2004, 20 nonanaplastic TC patients underwent IMRT. Mean age was 55. There were 3 T2 and 17 T4 patients. Sixteen patients had N1 disease. Seven patients had metastases before RT. Fifteen underwent surgery before RT. Radioactive iodine (RAI) and chemotherapy were used in 70% and 40%, respectively. Median total RT dose was 63 Gy. RESULTS: With two local failures, 2-year local progression-free rate was 85%. There were six deaths, with a 2-year overall survival rate of 60%. For patients with M0 disease, the 2-year distant metastases-free rate was 46%. The worst acute mucositis and pharyngitis was Grade 3 (n = 7 and 3, respectively). Two patients had Grade 3 acute skin toxicity and 2 had Grade 3 acute laryngeal toxicity. No significant radiation-related late effects were reported. CONCLUSIONS: IMRT for TC is feasible and effective in appropriately selected cases. Acute toxicity is manageable with proactive clinical care. Ideal planning target volume doses have yet to be determined. Additional patients and long-term follow-up are needed to confirm these preliminary findings and to clarify late toxicities.     

Re-irradiation of nasopharyngeal carcinoma with intensity-modulated radiotherapy.

BACKGROUND AND PURPOSE: To evaluate the treatment outcome in patients with locally recurrent nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). MATERIALS AND METHODS: Between October 2001 and May 2004, 31 patients with locally recurrent NPC received re-irradiation using IMRT. The rT classification distribution was 3 for rT1, 5 for rT2, 9 for rT3, and 14 for r T4. Median time from first course of radiotherapy to re-irradiation was 51 months. IMRT was performed using step-and-shoot method with nine 4-6 MV photon fields and median prescribed dose was 54 Gy (range: 50-60 Gy). Additional treatments included cisplatin-based induction chemotherapy in 68% and radiosurgery boost with a single dose which ranged from 8.5 to 12.5 Gy in 32%. Median follow-up time was 11 months. RESULTS: After re irradiation, 58% of patients had complete regression of primary tumor. One-year loco-regional progression-free, distant metastasis-free and overall survival rates were 56, 90, and 63%, respectively. Significantly better 1-year local progression-free rate was observed in rT1-3 than r T4 tumor (100 vs. 35%). Grade 3 late toxicities, mostly ototoxicity/cranial neuropathy, occurred in six patients (19%). One-year actuarial rates of late toxicities were 70% for all grades and 25% for Grade 3. CONCLUSION: Our preliminary results showed that good control of rT1-3 NPC can be achieved using IMRT with a dose between 50 and 60 Gy, whereas the outcome for r T4 tumor remained poor. Late toxicities were common but incidence of severe toxicities was relatively low.     

适形调强放疗同期整合瘤床推量治疗肺癌脑转移瘤的可行性研究

背景与目的：肺癌脑转移的发生率呈上升趋势,适形调强放射治疗(intensity-modulated radiotherapy,IMRT)+瘤床同期整合推量(simultaneous integrated boost,SIB)技术对于脑转移患者是一种新的治疗选择。本研究旨在探讨全脑IMRT+瘤床SIB治疗合并1~4个肺癌脑转移灶患者的近期临床疗效及治疗相关不良反应,明确该方案的可行性。方法：前瞻性收集2014年6月-2015年6月在江门市中心医院确诊为肺癌脑转移(转移病灶数1~4个)的32例患者,所有患者均行全脑5野IMRT(40 Gy/20 f)+瘤床SIB(50 Gy/20 f),分别评价其靶区剂量分布、放疗总有效率、肿瘤局部控制率、1年生存率、各种急性及晚期不良反应。结果：所有患者均完成放疗。全组2级呕吐、恶心和癫痫发生率分别为9.4%、15.6%和12.5%,2例出现2级认知功能障碍,4例出现2级记忆力损伤,2例出现3级记忆力损伤,无4级急性及晚期不良反应。放疗总有效率为71.9%,肿瘤局部控制率为96.9%,1年生存率为44%。结论：全脑5野IMRT(40 Gy/20 f)+瘤床SIB(共10 Gy,即总量50 Gy/20 f) 治疗1~4个肺癌脑转移灶是可行的。     

低位直肠癌术前调强放疗同步加量并同步口服卡培他滨化疗的初步研究

目的探讨低位直肠癌调强放射治疗（IMRT）同步加量并同步口服卡培他滨化疗的毒副作用,并初步分析其疗效。方法回顾性分析16例接受术前IMRT同步加量放疗同时口服希罗达化疗,临床诊断为T_（2～4）和/或N_（1～2）的低位直肠腺癌患者,放射治疗采用5野IMRT技术,共25次5周,全盆腔45～50Gy,肿瘤及其周围2cm范围同步加量至55～60Gy。同时口服卡培他滨625mg/m~2,每日2次,应用2周后休息1周,再继续口服至放疗结束。手术于放疗结束后8～10周进行。记录分析所有病例的毒副作用及远近期疗效。结果所有病例顺利完成治疗,无治疗中断者。有11例患者（68.8%）出现Ⅲ度皮肤反应,无Ⅲ度以上腹泻、血液学及泌尿系统毒副作用,仅1例患者（6.3%）出现晚期Ⅱ度胃肠道毒副作用。放疗后评估临床完全缓解7例（43.8%）,部分缓解8例（50%）。12例（75%）患者保肛,其中手术并保肛7例,肿物消失拒绝手术5例。2年总生存率85.7%,无病生存率76.6%,局部复发率6.3%。结论低位直肠癌调强放射治疗（IMRT）同步加量并同步口服卡培他滨化疗有一定效果且患者耐受良好,值得进一步探索研究。     

Three-dimensional intensity-modulated radiotherapy in the treatment of nasopharyngeal carcinoma: the University of California-San Francisco experience

PURPOSE: To review our experience with three-dimensional intensity-modulated radiotherapy (IMRT) in the treatment of nasopharyngeal carcinoma. METHODS AND MATERIALS: We reviewed the records of 35 patients who underwent 3D IMRT for nasopharyngeal carcinoma at the University of California-San Francisco between April 1995 and March 1998. According to the 1997 American Joint Committee on Cancer staging classification, 4 (12%) patients had Stage I disease, 6 (17%) had Stage II, 11 (32%) had Stage III, and 14 (40%) had Stage IV disease. IMRT of the primary tumor was delivered using one of the following three techniques: (1) manually cut partial transmission blocks, (2) computer-controlled autosequencing static multileaf collimator (MLC), and (3) Peacock system using a dynamic multivane intensity-modulating collimator (MIMiC). A forward 3D treatment-planning system was used for the first two methods, and an inverse treatment planning system was used for the third method. The neck was irradiated with a conventional technique using lateral opposed fields to the upper neck and an anterior field to the lower neck and supraclavicular fossae. The prescribed dose was 65-70 Gy to the gross tumor volume (GTV) and positive neck nodes, 60 Gy to the clinical target volume (CTV), and 50-60 Gy to the clinically negative neck. Eleven (32%) patients had fractionated high-dose-rate intracavitary brachytherapy boost to the primary tumor 1-2 weeks following external beam radiotherapy. Thirty-two (91%) patients also received cisplatin during, and cisplatin and 5-fluorouracil after, radiotherapy. Acute and late normal tissue effects were graded according to the Radiation Therapy Oncology Group (RTOG) radiation morbidity scoring criteria. Local-regional progression-free, distant metastasis-free survival and overall survival were estimated using the Kaplan-Meier method. RESULTS: With a median follow-up of 21.8 months (range, 5-49 months), the local-regional progression-free rate was 100%. The 4-year overall survival was 94%, and the distant metastasis-free rate was 57%. The worst acute toxicity was Grade 2 in 16 (46%) patients, Grade 3 in 18 (51%) patients and Grade 4 in 1 (3%) patient. The worst late toxicity was Grade 1 in 15 (43%), Grade 2 in 13 (37%), and Grade 3 in 5 (14%) patients. Only 1 patient had a transient Grade 4 soft-tissue necrosis. At 24 months after treatment, 50% of the evaluated patients had Grade 0, 50% had Grade 1, and none had Grade 2 xerostomia. Analysis of the dose-volume histograms (DVHs) showed that the average maximum, mean, and minimum dose delivered were 79.5 Gy, 75.8 Gy, and 56.5 Gy to the GTV, and 78.9 Gy, 71.2 Gy, and 45.4 Gy to the CTV, respectively. An average of only 3% of the GTV and 2% of the CTV received less than 95% of the prescribed dose. The average dose to 5% of the brain stem, optic chiasm, and right and left optic nerves was 48.3 Gy, 23.9 Gy, 15.0 Gy, and 14.9 Gy, respectively. The average dose to 1 cc of the cervical spinal cord was 41.7 Gy. The doses delivered were within the tolerance of these critical normal structures. The average dose to 50% of the right and left parotids, pituitary, right and left T-M joints, and ears was 43. 2 Gy, 41.0 Gy, 46.3 Gy, 60.5 Gy, 58.3 Gy, 52.0 Gy, and 52.2 Gy, respectively. CONCLUSION: 3D intensity-modulated radiotherapy provided improved target volume coverage and increased dose to the gross tumor with significant sparing of the salivary glands and other critical normal structures. Local-regional control rate with combined IMRT and chemotherapy was excellent, although distant metastasis remained unabated.     

Fatal pneumonitis associated with intensity-modulated radiation therapy for mesothelioma

PURPOSE: To describe the initial experience at Dana-Farber Cancer Institute/Brigham and Women's Hospital with intensity-modulated radiation therapy (IMRT) as adjuvant therapy after extrapleural pneumonectomy (EPP) and adjuvant chemotherapy. METHODS AND MATERIALS: The medical records of patients treated with IMRT after EPP and adjuvant chemotherapy were retrospectively reviewed. IMRT was given to a dose of 54 Gy to the clinical target volume in 1.8 Gy daily fractions. Treatment was delivered with a dynamic multileaf collimator using a sliding window technique. Eleven of 13 patients received heated intraoperative cisplatin chemotherapy (225 mg/m(2)). Two patients received neoadjuvant intravenous cisplatin/pemetrexed, and 10 patients received adjuvant cisplatin/pemetrexed chemotherapy after EPP but before radiation therapy. All patients received at least 2 cycles of intravenous chemotherapy. The contralateral lung was limited to a V20 (volume of lung receiving 20 Gy or more) of 20% and a mean lung dose (MLD) of 15 Gy. All patients underwent fluorodeoxyglucose positron emission tomography (FDG-PET) for staging, and any FDG-avid areas in the hemithorax were given a simultaneous boost of radiotherapy to 60 Gy. Statistical comparisons were done using two-sided t test. RESULTS: Thirteen patients were treated with IMRT from December 2004 to September 2005. Six patients developed fatal pneumonitis after treatment. The median time from completion of IMRT to the onset of radiation pneumonitis was 30 days (range 5-57 days). Thirty percent of patients (4 of 13) developed acute Grade 3 nausea and vomiting. One patient developed acute Grade 3 thrombocytopenia. The median V20, MLD, and V5 (volume of lung receiving 5 Gy or more) for the patients who developed pneumonitis was 17.6% (range, 15.3-22.3%), 15.2 Gy (range, 13.3-17 Gy), and 98.6% (range, 81-100%), respectively, as compared with 10.9% (range, 5.5-24.7%) (p = 0.08), 12.9 Gy (range, 8.7-16.9 Gy) (p = 0.07), and 90% (range, 66-98.3%) (p = 0.20), respectively, for the patients who did not develop pneumonitis. CONCLUSIONS: Intensity-modulated RT treatment for mesothelioma after EPP and adjuvant chemotherapy resulted in a high rate of fatal pneumonitis when standard dose parameters were used. We therefore recommend caution in the utilization of this technique. Our data suggest that with IMRT, metrics such as V5 and MLD should be considered in addition to V20 to determine tolerance levels in future patients.     

基于调强放疗N0期鼻咽癌颈部预防照射的选择

目的 探讨基于调强放疗(IMRT) N₀期鼻咽癌患者颈部预防照射的方式。方法 回顾分析2003—2008年本中心IMRT的 270例N₀期(第6版AJCC/UICC分期)初治鼻咽癌患者的临床资料,其中 171例接受上半颈预防照射,99例接受全颈预防照射。所有患者均接受鼻咽原发灶、上颈部淋巴引流区(包括双颈Ⅱ、Ⅲ、Ⅴ_A区)6 MV X线IMRT,鼻咽原发灶剂量为68 Gy分30次,上颈剂量为54 Gy分30次,疗程6周。全颈预防照射者下颈部及锁骨上采用颈前半野常规技术,剂量为50 Gy分25次。结果 中位随访65.1个月,随访率为93%。上颈、全颈预防照射的 5年肿瘤相关生存率分别为95.3%、91.9%(χ²=0.76,P=0.384),颈部无复发生存率分别为99.4%、99.0%(χ²=1.18,P=0.278),无远处转移生存率分别为98.8%、94.9%(χ²=2.31,P=0.128)。咽后淋巴结阴、阳性患者 5年无远处转移生存率分别为99.4%、93.7%(χ²=8.96,P=0.003)。急性不良反应主要为1、2级黏膜炎和咽喉炎,无3+4级张口困难和口干等晚期不良反应。结论 N₀期鼻咽癌患者IMRT时行上半颈预防照射也许是可行的,第7版AJCC/UICC将颈淋巴结阴性而咽后淋巴结阳性鼻咽癌上调为N₁是合理的。     

Individualized planning target volumes for intrafraction motion during hypofractionated intensity-modulated radiotherapy boost for prostate cancer

Purpose: The objective of the study was to access toxicities of delivering a hypofractionated intensity-modulated radiotherapy (IMRT) boost with individualized intrafraction planning target volume (PTV) margins and daily online correction for prostate position. Methods and materials: Phase I involved delivering 42 Gy in 21 fractions using three-dimensional conformal radiotherapy, followed by a Phase II IMRT boost of 30 Gy in 10 fractions. Digital fluoroscopy was used to measure respiratory-induced motion of implanted fiducial markers within the prostate. Electronic portal images were taken of fiducial marker positions before and after each fraction of radiotherapy during the first 9 days of treatment to calculate intrafraction motion. A uniform 10-mm PTV margin was used for the first phase of treatment. PTV margins for Phase II were patient-specific and were calculated from the respiratory and intrafraction motion data obtained from Phase I. The IMRT boost was delivered with daily online correction of fiducial marker position. Acute toxicity was measured using National Cancer Institute Common Toxicity Criteria, version 2.0. Results: In 33 patients who had completed treatment, the average PTV margin used during the hypofractionated IMRT boost was 3 mm in the lateral direction, 3 mm in the superior-inferior direction, and 4 mm in the anteroposterior direction. No patients developed acute Grade 3 rectal toxicity. Three patients developed acute Grade 3 urinary frequency and urgency. Conclusions: PTV margins can be reduced significantly with daily online correction of prostate position. Delivering a hypofractionated boost with this high-precision IMRT technique resulted in acceptable acute toxicity.     

Positron emission tomography-guided, focal-dose escalation using intensity-modulated radiotherapy for head and neck cancer

PURPOSE: To assess the feasibility of intensity-modulated radiotherapy (IMRT) using positron emission tomography (PET)-guided dose escalation, and to determine the maximum tolerated dose in head and neck cancer. METHODS AND MATERIALS: A Phase I clinical trial was designed to escalate the dose limited to the [(18)-F]fluoro-2-deoxy-D-glucose positron emission tomography ((18)F-FDG-PET)-delineated subvolume within the gross tumor volume. Positron emission tomography scanning was performed in the treatment position. Intensity-modulated radiotherapy with an upfront simultaneously integrated boost was employed. Two dose levels were planned: 25 Gy (level I) and 30 Gy (level II), delivered in 10 fractions. Standard IMRT was applied for the remaining 22 fractions of 2.16 Gy. RESULTS: Between 2003 and 2005, 41 patients were enrolled, with 23 at dose level I, and 18 at dose level II; 39 patients completed the planned therapy. The median follow-up for surviving patients was 14 months. Two cases of dose-limiting toxicity occurred at dose level I (Grade 4 dermitis and Grade 4 dysphagia). One treatment-related death at dose level II halted the study. Complete response was observed in 18 of 21 (86%) and 13 of 16 (81%) evaluated patients at dose levels I and II (p < 0.7), respectively, with actuarial 1-year local control at 85% and 87% (p = n.s.), and 1-year overall survival at 82% and 54% (p = 0.06), at dose levels I and II, respectively. In 4 of 9 patients, the site of relapse was in the boosted (18)F-FDG-PET-delineated region. CONCLUSIONS: For head and neck cancer, PET-guided dose escalation appears to be well-tolerated. The maximum tolerated dose was not reached at the investigated dose levels.     

Patterns of failure and toxicity after intensity-modulated radiotherapy for head and neck cancer

PURPOSE: To determine the outcome of patients treated with intensity-modulated radiotherapy (IMRT) for head and neck cancer. METHODS AND MATERIALS: We reviewed the charts of 100 consecutive patients treated with IMRT for squamous cell carcinoma of the oropharynx (64%), nasopharynx (16%), hypopharynx (14%), and larynx (6%). Most patients were treated with a concomitant boost schedule to 72 Gy. Of the 100 patients, 54 (54%) received adjuvant chemotherapy, mostly concurrent cisplatin. The dosimetry plans for patients with either locoregional failure or Grade 4-5 complications were reviewed and fused over the computed tomography images corresponding with the location of the event. Marginal failures were defined as those that occurred at a region of high-dose falloff, where conventional fields would have provided better coverage. RESULTS: The median follow-up of living patients was 3.1 years (range, 1-5.2 years). The 3-year rate of local control, locoregional control, freedom from relapse, cause-specific survival, and overall survival for all patients was 89%, 87%, 72%, 78%, and 71%, respectively. The 3-year rate of freedom from relapse, cause-specific survival, and overall survival for the 64 oropharynx patients was 86%, 92%, and 84%, respectively. Of the 10 local failures, 2 occurred at the margin of the high-dose planning target volume. Both regional failures occurred within the planning target volume. No locoregional failures occurred outside the planning target volume. Of the 100 patients, 8 and 5 had Grade 4 and 5 complications from treatment, respectively. All patients with Grade 5 complications had received adjuvant chemotherapy. No attempt was made to discriminate between the complications from IMRT and other aspects of the patients' treatment. CONCLUSION: Intensity-modulated radiotherapy did not compromise the outcome compared with what we have achieved with conventional techniques. The 2 cases of recurrence in the high-dose gradient region highlight the potential hazard of approaches that involve highly conformal dose distributions.     

Feasibility study of the simultaneous integrated boost (SIB) method for malignant gliomas using intensity-modulated radiotherapy (IMRT)

BACKGROUND: Intensity-modulated radiotherapy (IMRT) using the simultaneous integrated boost (SIB) method was designed for treating malignant gliomas. The purpose of this study was to investigate feasibility of this treatment. METHODS: Between December 2000 and November 2002, six patients with malignant gliomas were enrolled in this study. IMRT delivered 70 Gy/28 fractions (fr)/daily 2.5 Gy to the gross tumor volume (GTV) and 56 Gy/28 fr/daily 2.0 Gy to the surrounding edema defined as the clinical target volume annulus (CTV-a). The feasibility of the treatment was assessed from both physical and clinical points of view. RESULTS: No delay due to acute radiation toxicity was observed in any of the patients. The tumor recurred locoregionally in five of the six patients. The glioblastoma (GBM) recurred in two patients during the radiotherapy and in three patients at 5.4, 4.0 and 7.0 months after the start of radiotherapy. The sites of recurrence or progression were local in the GTV in four patients and in one patient subependymal dissemination was observed. Three patients, two with GBMs and one with anaplastic astrocytoma, died of the disease at 4, 16 and 7 months after the start of radiotherapy, respectively. CONCLUSIONS: The treatment of 70 Gy/28 fr/daily 2.5 Gy to the GTV and 56 Gy/28 fr/daily 2.0 Gy to the CTV-a was feasible both physically and clinically.     

Intensity-modulated radiotherapy for the treatment of vulvar carcinoma: a comparative dosimetric study with early clinical outcome

OBJECTIVES: To assess early clinical outcome of intensity-modulated radiation therapy (IMRT) in the treatment of vulvar cancer and compare dosimetric parameters with 3D conformal radiotherapy (3D CRT). METHODS: Fifteen patients with vulvar cancer were treated with IMRT. Seven patients were treated with preoperative chemoradiation, and 8 patients were treated with adjuvant postoperative radiation therapy. Median dose was 46 Gy in the preoperative and 50.4 Gy in the postoperative group. RESULTS: The mean volume of small bowel, rectum, and bladder that received doses in excess of 30 Gy with IMRT was reduced when compared with 3D CRT. Treatment was well tolerated, and only 1 patient had acute Grade 3 small-bowel toxicity. Median follow-up was 12 months. In the preoperative group, 5 patients (71%) had clinical complete response and 3 patients (42.8%) had pathologic complete response. In the adjuvant group, 2 patients had recurrences in the treatment field. No patients had late Grade 3 toxicity. The 2-year actuarial disease-specific survival was 100%. CONCLUSIONS: Intensity-modulated RT appears to offer advantages over 3D CRT treatment of vulvar cancer by elimination of dose modulation across overlapping regions and reduction of unnecessary dose to the bladder, rectum, and small bowel. Early results with a small number of patients show promising results, with a low incidence of severe toxicity.     

立体适形推量放射治疗在鼻咽癌首程放疗中的应用

目的：探索立体适形推量放射治疗在鼻咽癌首程放疗中的临床应用价值。方法：2000年5月～2002年9月，31例初治鼻咽癌患者，常规外照射至40～49天总量59～70Gy／30～35次后行立体适形推量放射治疗，以90％等剂量覆盖靶区，每次3～4Gy，每周3次，共治疗3～5次。其中15例每次3Gy，16例每次4Gy。结果：随访时间11～40月，中位随访时间23月，一、二年局控率分别为100％、90．81％，一、二年生存率分别为100％、94．44％，无严重放疗反应发生。结论：三维适形放射治疗作为推量技术应用于鼻咽癌首程放疗是可行的，并显示较好的局控和生存结果，远期疗效尚待进一步观察。     

Phase I trial of preoperative hypofractionated intensity-modulated radiotherapy with incorporated boost and oral capecitabine in locally advanced rectal cancer

PURPOSE: To determine the safety and efficacy of preoperative hypofractionated radiotherapy using intensity-modulated radiotherapy (IMRT) and an incorporated boost with concurrent capecitabine in patients with locally advanced rectal cancer. METHODS AND MATERIALS: The eligibility criteria included adenocarcinoma of the rectum, T3-T4 and/or N1-N2 disease, performance status 0 or 1, and age > or =18 years. Photon IMRT and an incorporated boost were used to treat the whole pelvis to 45 Gy and the gross tumor volume plus 2 cm to 55 Gy in 25 treatments within 5 weeks. The study was designed to escalate the dose to the gross tumor volume in 5-Gy increments in 3-patient cohorts. Capecitabine was given orally 825 mg/m(2) twice daily for 7 days each week during RT. The primary endpoint was the maximal tolerated radiation dose, and the secondary endpoints were the pathologic response and quality of life. RESULTS: Eight patients completed RT at the initial dose level of 55 Gy. The study was discontinued because of toxicity-six Grade 3 toxicities occurred in 3 (38%) of 8 patients. All patients went on to definitive surgical resection, and no patient had a pathologically complete response. CONCLUSION: This regimen, using hypofractionated RT with an incorporated boost, had unacceptable toxicity despite using standard doses of capecitabine and IMRT. Additional research is needed to determine whether IMRT is able to reduce the side effects during and after pelvic RT with conventional dose fractionation.