Intensity-modulated extended-field chemoradiation plus simultaneous integrated boost in the pre-operative treatment of locally advanced cervical cancer: a dose-escalation study

Objective:

To investigate the feasibility and determine the recommended pre-operative intensity-modulated radiotherapy (IMRT) dose of extended-field chemoradiation along with simultaneous integrated boost (SIB) dose escalation.

Methods:

A radiation dose of 40 Gy over 4 weeks, 2 Gy/fraction, was delivered to the tumour and the lymphatic drainage (planning target volume, PTV3), which encompassed a volume larger than standard (common iliac lymphatic area up to its apex, in front of the L3 vertebra), concurrently with chemotherapy (cisplatin and 5-fluorouracil). Radiation dose was escalated to the pelvis (PTV2) and to the macroscopic disease (PTV1) with the SIB-IMRT strategy. Three dose levels were planned: Level 1 (PTV3: 40/2 Gy; PTV2: 40/2 Gy; PTV1: 45/2.25 Gy), Level 2 (PTV3: 40/2 Gy; PTV2: 45/2.25 Gy; PTV1: 45/2.25 Gy) and Level 3 (PTV3: 40/2 Gy; PTV2: 45/2.25 Gy; PTV1: 50/2.5 Gy). All treatments were delivered in 20 fractions. Patients were treated in cohorts of between three and six per group using a Phase I study design. The recommended dose was exceeded if two of the six patients in a cohort experienced dose-limiting toxicity within 3 months from treatment.

Results:

19 patients [median age: 46 years; The International Federation of Gynecology and Obstetrics (FIGO) stage IB2: 3, IIB: 10, IIIA–IIIB: 6] were enrolled. Median follow-up was 24 months (9–60 months). The most common grade 3/4 toxicity was gastrointestinal (GI) (diarrhoea, mucous discharge, rectal/abdominal pain). At Levels 1 and 2, only one grade 3 GI toxicity per level was recorded, whereas at Level 3, two grade 3 GI toxicities (diarrhoea, emesis and nausea) were recorded.

Conclusion:

The SIB-IMRT technique was found to be feasible and safe at the recommended doses of 45 Gy to PTV1 and PTV2 and 40 Gy to PTV3 in the pre-operative treatment of patients with locally advanced cervical cancer. Unfortunately, this complex technique was unable to safely escalate dose beyond levels already achieved with three-dimensional conformal radiotherapy technique given acute GI toxicity.

Advances in knowledge:

A Phase I radiotherapy dose-escalation trial with SIB-IMRT technique is proposed in cervical cancer. This complex technique is feasible and safe at the recommended doses.     

简单调强高剂量或常规剂量放射治疗伴淋巴结转移的食管癌疗效分析

目的 探讨简单调强放疗技术(sIMRT)并同期化疗治疗颈段及胸上段食管癌,并予转移淋巴结高剂量放疗的可行性.方法 44例患者随机分为2组,高剂量组20例,常规剂量组24例.对颈及胸上段食管癌的原发灶和预防照射区进行sIMRT计划设计.定义3个靶区:PGTVnd为转移淋巴结靶区,高剂量组患者给予68.1 Gy,每次2.27 Gy,共30次;常规剂量组患者给予60 Gy,每次2.0 Gy,共30次.PTV1为需要加量照射的原发灶靶区,高剂量组给予63.9 Gy,每次2.13 Gy,共30次;常规剂量组60 Gy,每次2.0 Gy,共30次.PTV2为预防照射区,高剂量组和常规剂量组均给予54 Gy,每次1.8 Gy,共30次.放疗中顺铂(DDP)+5-氟尿嘧啶(5-FU)方案第1～5天和第29～33天同期化疗2个周期,放疗结束后28 d原方案重复2个疗程.结果 所有患者均完成了治疗计划,治疗中仅1例发生Ⅲ级放射性气管炎.高剂量组与常规剂量组淋巴结病灶达完全缓解(CR)者分别为75%(15/20)与45.8%(11/24),差异有统计学意义(x2=3.84,P＜0.05);1、2、3年无进展生存率分别为60%、40%、25%和41.7%、25%、8.3%(x2=4.11,P＜0.05);原发病灶近期疗效和1、2、3年生存率差异无统计学意义;不良反应主要为Ⅰ～Ⅱ级白细胞下降.结论 sIMRT计划治疗颈及胸上段食管癌,急性放射反应可耐受,给予转移淋巴结高剂量放疗可以提高患者的无复发生存率.

Abstract：

Objective To investigate the feasibility of simplified intensity-modulated radiotherapy (sIMRT) and concurrent chemotherapy against neck and upper thoracic esophageal carcinoma with lymph node metastasis.Methods sIMRT plans were designed for 44 patients of neck and upper thoracic esophageal carcinoma with lymph node metastasis, 20 of which underwent high dose sIMRT (hsIMRT group) and 24 underwent conventional dose sIM RT (csIMRT group).Three target volumes were defined:PGTVnd, target volume of lymph node lesion, irradiated to 68.1 Gy ( 2.27 Gy × 30 fractions ) for the hsIMRT group, and 60 Gy (2.0 Gy ×30 fractions) the csIMRT group; PTV1, the target volume of primary lesion, to be irradiate to 63.9 Gy (2.13 Gy × 30 fractions) for the hsIMRT group and 60 Gy (2.0 Gy × 30fractions) for the csIMRT group; PTV2 , the prophylacticly irradiated volume, to be irradiated to 54 Gy (1.8 Gy ×30) for both groups.The sIMRT plan included 5 equiangular coplanar beams.All patients received DDP + 5-FU regimen concurrently with radiotherapy at 1 -5 d and 29- 33 d, respectively.Chemotherapy was repeated for two cycles 28 days after the radiotherapy was finished.Results The treatment was completed for all patients within 6 weeks.During the treatment only one patient with grade 3 acute bronchitis was observed in the hsIMRT group.The complete response (CR) rate for the lymph node lesion of the hsIMRT group was 75% ( 15/20 ), significantly higher than that of the csIMRT group [45.8% ( 11/24), x2 = 3.84, P ＜ 0.05].The 1-, 2-, and 3-year progression-free survival rates of the hsIMRT group were 60%, 40%, and 25% , respectively,all significantly higher than those of the csIMRT group (41.7%, 25%, and 8.3% respectively, x2 = 4.11,P ＜ 0.05).However, there were not significant differences in the total survival rate, and the CR and PR of the esophageal lesion between these 2 groups.The major toxicity observed was grade Ⅰ -Ⅱ leukoctyopenia.Conclusions sIMRT generates desirable dose distribution for neck and upper thoracic esophageal carcinoma.hsIMRT has a better short-term efficacy than csIMRT.High dose radiotherapy toward metastatic lymph nodes helps increase progression-free survival.     

Intraindividual Comparison of Conventional Three-Dimensional Radiotherapy and Intensity Modulated Radiotherapy in the Therapy of Locally Advanced Non-Small Cell Lung Cancer

BACKGROUND: Local failure is the one of the most frequent cause of tumor related death in locally advanced non-small cell lung cancer (LAD-NSCLC). Dose escalation has the promise of increased loco-regional tumor control but is limited by the tolerances of critical organs. PATIENTS AND METHODS: To evaluate the potential of IMRT in comparison to conventional three-dimensional conformal planning (3DCRT) dose constraints were defined: Maximum dose (D(max)) to spinal cord < 48 Gy, mean lung dose 70 Gy in not more than 5 cm of the total length. For ten patients two plans were compared: (1) 3DCRT with 5 weekly fractions (SD) of 2 Gy to a total dose (TD) of 50 Gy to the planning target volume of second order (PTV2). If the tolerance of the critical organs was not exceeded, patients get a boost plan with a higher TD to the PTV1. (2) IMRT: concomitant boost with 5 weekly SD of 2 Gy (PTV1) and 1.5 Gy to a partial (p)PTV (pPTV=PTV2 profile of a line PTV1) to a TD of 51 Gy to the pPTV and 68 Gy to the PTV1. If possible, patients get a boost plan to the PTV1 with 5 weekly SD of 2 Gy to the highest possibly TD. RESULTS: Using 3DCRT, 3/10 patients could not be treated with TD > 50 Gy, but 9/10 patients get higher TD by IMRT. TD to the PTV1 could be escalated by 16% on average. The use of non-coplanar fields in IMRT lead to a reduction of the irradiated lung volume. There is a strong correlation between physical and biological mean lung doses. CONCLUSION: IMRT gives the possibility of further dose escalation without an increasing mean lung dose especially in patients with large tumors.     

68例食管癌三维适形放射治疗疗效观察

目的 探讨三维适形放射治疗(3D-CRT)食管癌的疗效.方法 采用3D-CRT治疗食管癌68例,常规分割2Gy/次,5次/周,总剂60～70Gy,6～7周.结果 1、3年局部控制率分别为80.9%和47.1%,1、3年生存率分别为76.4%和44.1%.毒副反应轻.结论 三维适形放射治疗食管癌能提高局部控制率和生存率,近期反应和远期反应均可耐受.     

Dosimetric study of optimal beam number and arrangement for treatment of nasopharyngeal carcinoma with intensity-modulated radiation therapy

The purpose of this dosimetric study was to evaluate the effect of beam number and arrangement on the dose distribution with intensity-modulated radiation therapy in patients with nasopharyngeal cancer. Computed tomography data sets of seven patients who were treated for nasopharyngeal carcinoma at the Peter MacCallum Cancer Centre were used for the present dosimetric study. The dose planned was 70 Gy in 7 weeks for the gross nasopharyngeal and nodal disease and the biological equivalents of 60 Gy in 6 weeks for the high-risk and 50 Gy in 5 weeks for the low-risk nodal disease. A plan using seven fields was compared to that using nine fields in all patients. Plans were assessed on the dose to the planning target volume (PTV) and the degree of parotid sparing achieved by evaluating both dose-volume histograms (DVH) and axial slices. Seven fields (three anterior and four posterior) provide good PTV coverage and satisfactory parotid sparing in patients with localized nasopharyngeal lesions. Nine fields appear to be better for tumours with significant posterolateral parapharyngeal extension. Parotid sparing is consistently better with nine fields. Both DVH and axial slices need to be evaluated before accepting any plan.     

Radiation therapy for the supraclavicular lymph node metastasis after curative resection of the esophageal carcinoma.

172 patients underwent curative resection for squamous cell carcinoma of the esophagus. The five-year actuarial survival rate was 38%. 21 of 27 patients who developed nodal metastasis of the supraclavicular lymph node were irradiated with a total dose of 40 to 70 Gy over four to seven weeks. This retrospective study showed the following results: 1. Complete response by radiation therapy was obtained 4/4 in tumor size within 2 cm, 7/10 in 2.1 to 5.0 cm with a total dose of 60 to 70 Gy, while 1/5 with a total dose of 40 to 56 Gy. 2. There were statistically significant differences of survival curves between multiple metastases and single metastasis of the supraclavicular lymph node (p less than 0.01).     

Prediction of tumor control by tumor regression at 40 Gy/4 weeks of external beam irradiation for oropharyngeal carcinoma

PURPOSE: To predict tumor control on the basis of tumor regression at 40 Gy/4 weeks of external beam radiotherapy (EBRT) for oropharyngeal carcinoma. METHODS: From 1990 to 1997, 55 patients (9 Stage I+II, 15 Stage III, and 31 Stage IV) with squamous cell carcinoma of the oropharynx were treated with curative EBRT (median dose, 66 Gy). Tumor response at 4 weeks was compared with loco-regional control. RESULTS: The five-year loco-regional control rate was 52%. Regression of primary tumors was more rapid and occurred at a rate higher than that of nodal lesions; however, nodal response served as a superior predictor of tumor control. Predictive factors for loco-regional control were tumor stage, loco-regional response at 4 weeks, and pathological differentiation. Stage III and non-well-differentiated stage IV tumors demonstrating >50% regression at 4 weeks were controlled initially at 74% (17/23) and ultimately at 83% (19/23) by salvage therapy. In contrast, stage III+IV tumors displaying <50% regression and well-differentiated stage IV tumors exhibiting >50% regression were controlled initially at 9% (2/23) and ultimately at 22% (5/23). CONCLUSION: Tumor regression at 40 Gy/4 weeks of EBRT is an important parameter in terms of prediction of loco-regional control for stage III and IV disease.     

Intraindividual Comparison of Conventional Three-Dimensional Radiotherapy and Intensity Modulated Radiotherapy in the Therapy of Locally Advanced Non-Small Cell Lung Cancer A Planning Study

Background: Local failure is the one of the most frequent cause of tumor related death in locally advanced non-small cell lung cancer (LAD-NSCLC). Dose escalation has the promise of increased loco-regional tumor control but is limited by the tolerances of critical organs. Patients and Methods: To evaluate the potential of IMRT in comparison to conventional three-dimensional conformal planning (3DCRT) dose constraints were defined: Maximum dose (D_max) to spinal cord < 48 Gy, mean lung dose h 24 Gy, D_max esophagus > 70 Gy in not more than 5 cm of the total length. For ten patients two plans were compared: (1) 3DCRT with 5 weekly fractions (SD) of 2 Gy to a total dose (TD) of 50 Gy to the planning target volume of second order (PTV2). If the tolerance of the critical organs was not exceeded, patients get a boost plan with a higher TD to the PTV1. (2) IMRT: concomitant boost with 5 weekly SD of 2 Gy (PTV1) and 1.5 Gy to a partial (p)PTV (pPTV=PTV2 š PTV1) to a TD of 51 Gy to the pPTV and 68 Gy to the PTV1. If possible, patients get a boost plan to the PTV1 with 5 weekly SD of 2 Gy to the highest possibly TD. Results: Using 3DCRT, 3/10 patients could not be treated with TD > 50 Gy, but 9/10 patients get higher TD by IMRT. TD to the PTV1 could be escalated by 16% on average. The use of non-coplanar fields in IMRT lead to a reduction of the irradiated lung volume. There is a strong correlation between physical and biological mean lung doses. Conclusion: IMRT gives the possibility of further dose escalation without an increasing mean lung dose especially in patients with large tumors. Hintergrund: Lokale Rezidive sind eine häufige Todesursache bei Patienten mit lokal fortgeschrittenen nichtkleinzelligen Bronchialkarzinomen (LAD-NSCLC). Dosiseskalation verspricht hier eine Verbesserung der lokalen Kontrolle, ist aber limitiert durch die Toleranz der Nachbarstrukturen. Patienten und Methoden: Um das Potential der IMRT im Vergleich zur konventionellen 3-D-Planung herauszuarbeiten, wurden folgende Dosis-Volumen-Vorgaben definiert: Maximale Dosis (D_max) des Myelons < 48 Gy, mittlere Lungendosis (MLD) h 24 Gy, D_max des Ösophagus > 70 Gy in h 5 cm der Gesamtlänge. Für zehn Patienten mit LAD-NSCLC wurden verglichen: 1. 3DCRT mit fünf wöchentlichen Einzeldosen (ED) von 2 Gy bis zu einer Gesamtdosis (GD) von 50 Gy für das Planungszielvolumen zweiter Ordnung (PTV2). Wenn die Toleranz der umliegenden Gewebe dies zuließ, erhielten die Patienten einen Boostplan für das PTV1. 2. IMRT: Concomitant Boost mit fünf söchentlichen ED von 2 Gy für das PTV1 und 1,5 Gy für das partielle PTV (pPTV=PTV2 š PTV1) bis zu einer GD von 51 Gy im pPTV und 68 Gy im PTV1. Falls die Belastung des Normalgewebes dies erlaubte, erfolgte ein Boostplan für das PTV1 mit fünf wöchentlichen ED von 2 Gy bis zur höchstmöglichen GD. Ergebnisse: Konventionell konnten 3/10 Patienten mit GD > 50 Gy behandelt werden - mittels IMRT konnten bei 9/10 Patienten höhere Dosen appliziert werden. Im PTV1 konnte im Mittel eine Dosiseskalation von 16% erreicht werden. Besonders Patienten mit großen Tumoren profitierten von der IMRT. Die Verwendung nonkoplanarer Techniken führte zur Verringerung der Dosis innerhalb des kritischen Lungenvolumens. Die physikalischen mittleren Lungendosen waren hoch korreliert mit den biologisch gewichteten mittleren Lungendosen. Schlussfolgerung: Im Vergleich zur 3DCRT ermöglicht die IMRT eine Dosiseskalation in der Behandlung von LAD-NSCLC ohne Erhöhung der mittleren Lungendosis. Von der Technik profitieren insbesondere Patienten mit größeren Tumoren.     

Phase I Trial of Radiochemotherapy with Bendamustine in Patients with Recurrent Squamous Cell Carcinoma of the Head and Neck

BACKGROUND AND PURPOSE: After initial radiochemotherapy of head-and-neck cancers, therapeutic options are often limited for patients with progressive disease. Reirradiation, with or without chemotherapy, appears to be the most potential treatment option. The aim of this study was to determine the maximum tolerated dose of bendamustine in combination with reirradiation for these patients. PATIENTS AND METHODS: 13 patients with recurrent squamous cell carcinoma of the head-and-neck region after initial radiochemotherapy were treated. Reirradiation of the recurrent region under protection of the spinal cord consisted of 1.8 Gy given five times per week, up to 30.6 Gy. Simultaneous bendamustine was administered on days 1 and 2 at increasing dose levels (80, 100, and 120 mg/m(2) bendamustine). The regimen was administered every 4 weeks. A minimum of three patients were enrolled at each dose level. RESULTS: The therapy was well tolerated. Patients received one to six cycles of bendamustine (median: three). Hematologic toxicities observed were leukocytopenia, thrombocytopenia, or anemia. At dose level II (100 mg/m(2) bendamustine), grade 3/4 hematologic toxicity was seen in one patient so that this level was filled up to six patients. There was no grade 3/4 toxicity seen in the other twelve patients. The most frequent nonhematologic toxicities (grade 1 or 2) were infections (in most cases C-reactive protein elevations without other clinical signs of infection) and nausea. CONCLUSION: The reapplication of radiochemotherapy with bendamustine is well tolerated. The recommended dose for phase II studies was established at dose level III (bendamustine 120 mg/m(2)).     

Simultaneous Integrated Boost (SIB) for Nasopharynx Cancer with Helical Tomotherapy

PURPOSE: To explore the potential of helical tomotherapy (HT) in the treatment of nasopharynx cancer. PATIENTS AND METHODS: Six T1-4 N1-3 patients were considered. A simultaneous integrated boost (SIB) technique was planned with inversely optimized conventional intensity-modulated radiotherapy (IMRT; dynamic multileaf collimator using the Eclipse-Helios Varian system) and HT. The prescribed (median) doses were 54 Gy, 61.5 Gy, and 64.5 Gy delivered in 30 fractions to PTV1 (planning target volume), PTV2, and PTV3, respectively. The same constraints for PTV coverage and for parotids, spinal cord, mandible, optic structures, and brain stem were followed in both modalities. The planner also tried to reduce the dose to other structures (mucosae outside PTV1, larynx, esophagus, inner ear, thyroid, brain, lungs, submental connective tissue, bony structures) as much as possible. RESULTS: The fraction of PTV receiving >95% of the prescribed dose (V95%) increased from 97.6% and 94.3% (IMRT) to 99.6% and 97% (HT) for PTV1 and PTV3, respectively (p<0.05); median dose to parotids decreased from 30.1 Gy for IMRT to 25.0 Gy for HT (p<0.05). Significant gains (p<0.05) were found for most organs at risk (OARs): mucosae (V30 decreased from 44 cm(3) [IMRT] to 18 cm(3) [HT]); larynx (V30: 25 cm(3) vs. 11 cm(3)); thyroid (mean dose: 48.7 Gy vs. 41.5 Gy); esophagus (V45: 4 cm(3) vs. 1 cm(3)); brain stem (D1%: 45.1 Gy vs. 37.7 Gy). CONCLUSION: HT improves the homogeneity of dose distribution within PTV and PTV coverage together with a significantly greater sparing of OARs compared to linac five-field IMRT.     

Reducing the Risk of Xerostomia and Mandibular Osteoradionecrosis: The Potential Benefits of Intensity Modulated Radiotherapy in Advanced Oral Cavity Carcinoma

Radiation therapy for squamous cell carcinoma of the oral cavity may be curative, but carries a risk of permanent damage to bone, salivary glands, and other soft tissues. We studied the potential of intensity modulated radiotherapy (IMRT) to improve target volume coverage, and normal tissue sparing for advanced oral cavity carcinoma (OCC). Six patients with advanced OCC requiring bilateral irradiation to the oral cavity and neck were studied. Standard 3D conformal radiotherapy (3DCRT) and inverse-planned IMRT dose distributions were compared by using dose-volume histograms. Doses to organs at risk, including spinal cord, parotid glands, and mandible, were assessed as surrogates of radiation toxicity. PTV1 mean dose was 60.8 ± 0.8 Gy for 3DCRT and 59.8 ± 0.1 Gy for IMRT (p = 0.04). PTV1 dose range was 24.7 ± 6 Gy for 3DCRT and 15.3 ± 4 Gy for IMRT (p = 0.001). PTV2 mean dose was 54.5 ± 0.8 Gy for 3DCRT and for IMRT was 54.2 ± 0.2 Gy (p = 0.34). PTV2 dose range was improved by IMRT (7.8 ± 3.2 Gy vs. 30.7 ± 12.8 Gy, p = 0.006). Homogeneity index (HI) values for PTV2 were closer to unity using IMRT (p = 0.0003). Mean parotid doses were 25.6 ± 2.7 Gy for IMRT and 42.0 ± 8.8 Gy with 3DCRT (p = 0.002). The parotid V30 in all IMRT plans was <45%. The mandible V50, V55, and V60 were significantly lower for the IMRT plans. Maximum spinal cord and brain stem doses were similar for the 2 techniques. IMRT provided superior target volume dose homogeneity and sparing of organs at risk. The magnitude of reductions in dose to the salivary glands and mandible are likely to translate into reduced incidence of xerostomia and osteoradionecrosis for patients with OCC.     

Ⅰb和Ⅱ期宫颈癌术后调强放疗的疗效

 目的 总结Ⅰb和Ⅱ期宫颈癌术后调强放疗的疗效。方法 回顾分析2008-01至2012-02收治的83例手术+术后放疗的宫颈癌临床病例资料,放疗剂量50 Gy/25次/5周,所有病例术后均接受2～4周期以铂类为基础的化疗,分析指标主要有生存率、无瘤生存率、局部控制率及不良反应等。结果 所有患者均顺利完成治疗,随访率为100％。全组3年总生存率为89.2％,无瘤生存率为83.1％,盆腔局部控制率为85.5％。腺癌和鳞癌的总生存率分别为50％和91％(χ²=9.65,P=0.002)。肠道反应1、2级发生率为10.34％,泌尿系反应1、2级发生率为10.34％,外周血白细胞计数下降1、2级发生率为58.62％,无4级不良反应。结论 Ⅰb和Ⅱ期宫颈癌术后具有不良预后因素者行调强放疗具有较高的生存率和局部控制率,不良反应可耐受。     

Concurrent Radiochemotherapy of Locally Recurrent or Advanced Sarcomas of the Uterus

BACKGROUND: Uterine sarcomas are rare tumors. Until now, no data on the treatment of recurrent or advanced uterine sarcomas using concurrent radiochemotherapy (RCT) has been available. PATIENTS AND METHODS: From 01/1997 to 03/2004, seven patients with locally recurrent (n = 6) or locally advanced uterine sarcomas (n = 1) received concurrent RCT after tumor surgery (R1/2 resection in 3/7 patients). A total radiation dose of 45 Gy was applied in single doses of 1.8 Gy using an external-beam technique; in addition, three to four intracavitary doses of 5 Gy were applied. Concurrent chemotherapy was generally administered as follows: 1.2 g/m(2) ifosfamide on days 1-5 and 29-33 in combination with 50 or 40 mg/m(2) adriamycin on days 2 and 30. 3/7 patients received further cycles of chemotherapy. The median follow- up was 35 months. RESULTS: All recurrences (before RCT) were localized either in the vagina or in or directly proximal to the vaginal stump. The main side effects of RCT were hemotoxicity (grade 3: n = 3/7; grade 4: n = 4/7; neutropenic fever n = 1/7) and diarrhea (grade 3: n = 5/7). At the median follow-up (35 months), 4/7 patients had recurrences (one local recurrence; one lymph node recurrence outside the irradiated field, two distant metastases). Local control in the irradiated field was 80% +/- 18% after 3 years. Disease-free survival calculated according to Kaplan-Meier was 57% +/- 19% after 3 years. Presently, 5/7 patients are still alive, corresponding to a 3-year survival rate of 83% +/- 15%. CONCLUSION: Concurrent RCT shows good local effectiveness with a good long-term survival. Further evaluation in phase II studies is recommended.     

Hypofractionated Stereotactic Radiotherapy for Primary and Secondary Intrapulmonary Tumors

PURPOSE: To evaluate the feasibility, efficacy, and side effects of dose escalation in hypofractionated stereotactic radiotherapy (hfSRT) for intrapulmonary tumors with the Novalis system (BrainLAB AG, Heimstetten, Germany). PATIENTS AND METHODS: From 07/2003 to 01/2005, 21 patients/39 tumors were treated with 5 x 7 Gy (n = 21; total dose 35 Gy) or 5 x 8 Gy (n = 18; total dose 40 Gy). There were three cases of primary lung cancer, the remainder were metastases. Median gross tumor volume (GTV) and planning target volume (PTV) were 2.89 cm(3) (range, 0.15-67.94 cm(3)) and 25.75 cm(3) (range, 7.18-124.04 cm(3)), respectively. RESULTS: Rates of complete remission, partial remission, no change, and progressive disease were 51%, 33%, 3%, and 13%, respectively. No grade 4 toxicity occurred, nearly all patients had grade 1 initially. One grade 3 toxicity, i.e., dyspnea, was documented for a period of 6 months after therapy. Radiosurgery quality assurance guidelines could be met. CONCLUSION: hfSRT of primary and secondary lung tumors using a schedule of five fractions at 7-8 Gy each was well tolerated. Further dose escalation is planned.     

Etablierung einer 3D-Konformationstechnik zur Radio therapie von Kopf-Hals-Tumoren unter Berücksichtigung der Parotisschonung

PURPOSE: The aim of this study was to improve the irradiation technique for the treatment of head-and-neck tumors and, in particular, to make use of the advantages found in modern 3D planning to protect the parotid glands. PATIENTS AND METHODS: For this investigation the 3D dataset of a standard patient with oropharyngeal carcinoma of UICC stage IVA was used. In the CT scans (slice thickness 5 mm) the planning target volume (PTV), the boost volume and both parotids were delineated. Three different techniques were calculated for two different dose levels (50 Gy for PTV and 64 Gy for boost volume, using single doses of 2 Gy). For technique 1 (T1) a parallel opposed field photon/electron irradiation was designed, for technique 2 (T2) an opposed/arc field irradiation was employed, and for technique 3 (T3) a combination of a static coplanar and arc field irradiation was designed. The sum doses D(min), D(max) and D(mean) for PTV, boost volume, and ipsilateral and contralateral parotid gland were evaluated, and the time needed for calculation of the plans was also determined. RESULTS: For all techniques used, the calculated doses in the PTV (D(min) 5.6 +/- 0.1 Gy, D(max) 73.7 +/- 0.1 Gy, and D(mean) 57.9 +/- 0.5 Gy) and in the boost volume (D(min) 46.9 +/- 1.5 Gy, D(max) 73.8 +/- 0.12 Gy, and D(mean) 65.8 +/- 0.9 Gy) were equal. Significant differences were found regarding the three different techniques, e.g., for the ipsilateral parotid gland D(min) (T1 = 47.4, T2 = 50.6, and T3 = 38.4 Gy) as well as for the contralateral parotid gland D(min) (T1 = 42.1, T2 = 44.2, and T3 = 17.8 Gy) and D(mean) (T1 = 51.3, T2 = 52.8, and T3 = 32.6 Gy). Regarding the three different techniques, significant differences were found in favor of T3. The determined planning times were as follows: T1 = 90, T2 = 60, and T3 = 90 min. CONCLUSION: The combination of static coplanar and arc field technique (T3) resulted in a substantially better protection as compared to both other techniques. This was especially the case with regard to the contralateral parotid gland, when the dose distributions were calculated equally for PTV and boost volume. In this study, the D(mean) dose of the contralateral parotid gland was lower than the TD(50) of 37 Gy (95% confidence interval 32-43 Gy) previously assumed by the authors. Therefore, it can be concluded that in the present study a more intensive protection of this gland and a reduction in xerostomia were possibly obtained.     

Multisegmented Tangential Breast Fields: a Rational Way to Treat Breast Cancer

PURPOSE: Using three-dimensional conformal radiation therapy (3D-CRT) and multisegmented conformal radiation therapy (MS-CRT) for breast cancer treatment, the dose coverage of the planning target volume (PTV) and the radiation burden on the organs at risk (OARs) were evaluated. MATERIAL AND METHODS: 3D-CRT and MS-CRT were planned for 436 unilateral breasts (217 left). All patients were treated with MS-CRT between 2005 and 2007. For PTV delineation and beam orientation, supportive structures were applied. The mean PTV was 1,130 cm3 (in ten patients > 2,200 cm3). Three-dimensional planning with weight-optimized medial and lateral open fields at a total dose of 50.4/1.8 Gy was followed by multisegmented planning with a reasonably high-dose-level dose cloud to define the medial subfield, and renewed optimization. This was repeated for the lateral subfield with a final optimization. For PTV coverage evaluation, the ICRU 50 was considered: the PTV portions receiving 95-107%, < 95% and > 107% of the prescribed dose (PTVD95- 107%, PTVD107%), and the PTV maximal dose (PTVDmax). To compare the OAR radiation burdens, the mean doses to the ipsi-/contralateral lung, contralateral breast, and whole heart were documented. RESULTS: The multisegmented plans furnished significantly (p < 0.0001) better target coverage (PTVD95-107% 82.8% vs. 90.9%, PTVD107% 5.9% vs. 0.3% and PTVDmax 56.6 vs. 54.3 Gy). The mean OAR doses remained almost unchanged: ipsilateral lung 10.5 versus 10.4 Gy, contralateral lung 0.4 versus 0.4 Gy, contralateral breast 0.8 versus 0.8 Gy, and whole heart (for left-sided cancers) 4.8 versus 4.8 Gy. The subfields required a mean of 9.8 MU (monitor units), i.e., a mean total 7.6 MU increment. The planning took 10-20 min, and the delivery 5-10 min. CONCLUSION: MS-CRT is a good alternative to breast intensity-modulated radiation therapy (IMRT) and seems adequate for right-sided cancers, whereas left-sided cancers necessitate a longer follow-up of heart-related side effects before a final assessment.     

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 cm(3) (4-170 cm(3)), mean nodal volume 16.6 cm(3) (0-97 cm(3)). 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 structures.