An interlaced IMRT technique for elongated tumor volumes.

Treatment of large target volumes with intensity modulated radiotherapy (IMRT) can be restricted by the maximum field size of the multileaf collimator (MLC). In this work, a straightforward technique for MLC-based IMRT is presented, which is generally applicable and does not depend on the capabilities of the linear accelerator's IMRT delivery system. A dual isocenter technique was developed that maximizes beam overlap. The beams at the first isocenter are arranged such that they interlace with the beams at the second isocenter. All beams contribute to the overlap region, whereas only some contribute to the superior and some to the inferior part of the target. The interlaced technique (9 beams) was compared with an alternative more complex approach (14 beams) for a head-and-neck case with simultaneous integrated boost and 3 different dose levels. The plans were compared in terms of complexity, dosimetry, and the effect of inaccurate translation between the isocenters. The interlaced and the more complex IMRT technique resulted in nearly identical dose distributions without clinically relevant differences. The total number of monitor units (MUs) was comparable with more MUs per segment for the interlaced technique. For the interlaced technique, the number of segments

Radiotherapy in adrenocortical carcinoma.

Adrenocortical carcinoma (ACC) is a rare malignancy, and patients with ACC have a poor prognosis. Even after radical surgery, up to 85% of patients develop recurrent disease. Systemic treatment options still have limited efficacy. Because the role of radiotherapy is not defined well and because ACC often is considered radioresistant, the authors reviewed the available data on radiotherapy for ACC. Original articles and reviews were identified using a PubMed search strategy that included the period up to July 2008. Ten articles were identified that covered radiotherapy in a total of 129 patients with ACC (64 patients received postoperative irradiation, and 65 patients received palliative therapy for advanced disease). In addition, 26 patients were identified in the German ACC Registry who received palliative radiotherapy. Furthermore, patterns of failure after adjuvant radiotherapy were investigated, and the authors provided recommendations for patient selection, treatment planning, and treatment protocols. In an adjuvant setting, postoperative radiotherapy was able to prevent local recurrence in the majority of patients. In those with advanced disease, a response to radiotherapy was observed in 57% of patients who received palliative radiotherapy. Therefore, the authors concluded that radiotherapy may play an important role in the care of patients with ACC. Until better evidence is available, the authors recommended the following approach: Adjuvant radiotherapy to the tumor bed should be considered in patients at high risk for local recurrence (eg, incomplete/R1 resection); a total dose of >40 grays (Gy) with single fractions of 1.8 Gy to 2 Gy should be administered (including a boost volume to reach from 50 Gy to 60 Gy in individual patients); and radiotherapy in a palliative setting may be used for symptomatic metastases to bone, brain, or vena cava obstruction. With state-of-the-art technology, acute and long-term toxicities mostly were mild to moderate. However, the authors concluded that prospective investigations would be required to fully define the therapeutic potential of this important treatment option.

Induction chemotherapy with paclitaxel and cisplatin followed by radiotherapy for larynx organ preservation in advanced laryngeal and hypopharyngeal cancer offers moderate late toxicity outcome (DeLOS-I-trial).

A prospective multicenter phase-II trial (12 centers) was performed by the German larynx organ preservation group (DeLOS) to evaluate the effect of induction chemotherapy (ICHT) with paclitaxel/cisplatin (TP), followed by accelerated-hyperfractionated (concomitant boost) radiotherapy (RT) in responders. The trial was focused on larynx preservation, tumor control, survival, salvage surgery and late toxicity in patients with advanced larynx/hypopharynx carcinoma eligible for total laryngectomy (LE). Seventy-one patients (40 larynx, 87.5% St. III, IV; 31 hypopharynx, 93.4% St. III, IV) were enrolled into the study and treated with ICHT (200 mg/m(2) paclitaxel, 100 mg/m(2) cisplatin; day 1, 22) according to the DeLOS protocol. Patients with complete or partial tumor response proceeded to RT (69.9 Gy in 5.5 weeks). Non-responders received a LE followed by postoperative RT (56-70 Gy in 5.5-7 weeks). The response rate to ICHT for larynx cancer was 69.6% (7.1% complete, 62.5% partial response) and for hypopharyngeal cancer was 84.3% (6.9% complete, 77.4% partial response). Overall survival after 36 months was 60.3% (95% CI, 48.4-72.2%), after 42 months was 56.5% (95% CI, 44.2-68.8%). Laryngectomy-free survival was as follows: after 36 months, 43.0% (95% CI, 30.9-55.0%); after 42 months, 41.3% (95% CI, 29.3-53.3%). Both parameters did not show different outcomes after distinguishing larynx from hypopharynx. LE was indicated in 15 non-responders after ICHT. Five of the 15 non-responders refused the laryngectomy. Two of the five received RT instead and had no evidence of disease 42 months after RT. Late toxicity (dysphagia III, IV LENT SOMA score in laryngectomy-free survivors: after 6 months, 1.8%; 12 months, 11.4%; 18 months, 14.5%; 24 months, 8.1%; 36 months, 16%) and salvage surgery (4 pharyngocutaneous fistulas in 27 operations) were tolerable. In a large portion of patients eligible for LE, the larynx could be preserved with satisfying functional outcome. Good responders after ICHT had also a good general outcome with relatively rare severe late toxicities. Due to a slight increase of relevant late dysphagia, functional outcome regarding swallowing and tracheotomy free breathing should be more focused in future larynx organ preservation trials.

A comparison between 2-Step IMRT and conventional IMRT planning.

BACKGROUND AND PURPOSE: 2-Step intensity modulated radiation therapy (2-Step IMRT) is an IMRT segmentation procedure based on analytical approximations [Bratengeier K. 2-Step IMAT and 2-Step IMRT: a geometrical approach. Med Phys 2005;32:777-785; Bratengeier K. 2-Step IMAT and 2-Step IMRT in three dimensions. Med Phys 2005;32:3849-3861]. The aim was to benchmark it with other IMRT algorithms and to establish it as planning tool for fast IMRT application with a reduced number of segments. MATERIALS AND METHODS: 2-Step IMRT plans were compared with IMRT-solutions obtained with methods from a commercial planning system (Pinnacletrade mark TPS). The four clinical cases chosen were: paraspinal tumour, carcinoma of the prostate, head and neck carcinoma and breast carcinoma. In addition the "Quasimodo" phantom study was used to compare the quality of the 2-Step IMRT method with respect to other planning procedures in the ESTRO study. RESULTS: The number of segments (and - to a minor degree - the monitor units per dose) of the majority of 2-Step IMRT plans was lower than for the commercial algorithms. The quality of the 2-Step IMRT-plan was comparable. In the Quasimodo comparison 2-Step IMRT plans with nine beams would place in the mid-range of all participants, whereas the 15-beam arrangements could compete with the best results. CONCLUSIONS: 2-Step IMRT is a valuable IMRT segmentation method, especially if the number of segments is to be limited (e.g. for reasons of precision, speed and leakage radiation).

Hyperfractionated accelerated radiotherapy in combination with weekly cisplatin for locally advanced head and neck cancer.

BACKGROUND: The purpose of this study was to determine the feasibility and efficacy of hyperfractionated accelerated radiotherapy (HFRCB) combined with simultaneous chemotherapy with weekly cisplatin (CDDP) in locally advanced inoperable head and neck cancer. METHODS: From August 1999 to December 2002, 37 patients (median age, 59 years) with Union Internationale Contre le Cancer stage III (n = 2) and stage IV (n = 35) squamous cell cancer of the oropharynx and hypopharynx were treated in a prospective phase I/II trial. Concomitant boost radiotherapy (1.8 Gy, days 1-38 and 1.5 Gy boost, days 22-38, twice daily with at least a 6-hour interval; total dose 69.9 Gy) and simultaneous cisplatin, 40 mg/m2 weekly, were given. RESULTS: The median treatment duration was 42 days (range, 38-46 days). Toxicity was manageable, with neutropenia grade III/IV and thrombocytopenia grade IV in seven and one patients, and mucositis grade III/ IV in 27 and five patients, respectively. Chemotherapy was restricted to four weekly applications in 29 patients mainly because of mucosal toxicity with a median dose intensity of 160 mg/m2 (0-200) of cisplatin in 5.5 weeks. With a median follow-up of 28 months for living patients, the 2-year overall survival rate was 67%. The median overall and relapse-free survival times were 36 and 31 months, respectively. CONCLUSION: HFRCB in combination with weekly cisplatin achieves a high rate of locoregional control and survival. Four weekly cycles of 40 mg/m2 cisplatin seem to be the dose limit for most patients.

Induction chemotherapy with paclitaxel and cisplatin and CT-based 3D radiotherapy in patients with advanced laryngeal and hypopharyngeal carcinomas--a possibility for organ preservation.

BACKGROUND: To evaluate the effect of paclitaxel/cisplatin induction chemotherapy (ICHT) and CT-based radiotherapy (RT) on larynx preservation, tumor control, and survival in patients with larynx/hypopharynx carcinoma eligible for total laryngectomy (TL) or TL plus partial pharyngectomy (TLPP). PATIENTS AND METHODS: Fifty patients eligible for TL or TLPP were enrolled onto a prospective study and treated with ICHT (200 mg/m(2) paclitaxel, 100 mg/m(2) cisplatin; day 1, 22). In patients with complete or partial tumor response RT (69.9 Gy in 5.5 weeks at the gross tumor, 50.4 Gy in the lymphatic drainage; single dose: 1.8 Gy, concomitant boost: 1.5 Gy) was applied. Non-responders had TL/TLPP and RT with total doses adapted to the radicality of tumor resection (56-70 Gy). RESULTS: The response rate to ICHT was 88% (10% complete, 78% partial response). At a median follow-up period of 25 months the larynx preservation rate was 84%. The 2-year local-regional control rate was 91% and the 2-year overall survival rate was 72.3%. The 3-year estimate to survive with functional larynx is 60%. CONCLUSION: In a large portion of patients eligible for TL or TLPP the larynx was preserved by paclitaxel/cisplatin ICHT and 3D RT.