On the Importance of Individualized, Non-Coplanar Beam Configurations in Mediastinal Lymphoma Radiotherapy, Optimized With Automated Planning.

BACKGROUND AND PURPOSE: Literature is non-conclusive regarding selection of beam configurations in radiotherapy for mediastinal lymphoma (ML) radiotherapy, and published studies are based on manual planning with its inherent limitations. In this study, coplanar and non-coplanar beam configurations were systematically compared, using a large number of automatically generated plans. MATERIAL AND METHODS: An autoplanning workflow, including beam configuration optimization, was configured for young female ML patients. For each of 25 patients, 24 plans with different beam configurations were generated with autoplanning: 11 coplanar CP_x plans and 11 non-coplanar NCP_x plans with x = 5 to 15 IMRT beams with computer-optimized, patient-specific configurations, and the coplanar VMAT and non-coplanar Butterfly VMAT (B-VMAT) beam angle class solutions (600 plans in total). RESULTS: Autoplans compared favorably with manually generated, clinically delivered plans, ensuring that beam configuration comparisons were performed with high quality plans. There was no beam configuration approach that was best for all patients and all plan parameters. Overall there was a clear tendency towards higher plan quality with non-coplanar configurations (NCP_x≥12 and B-VMAT). NCP_x≥12 produced highly conformal plans with on average reduced high doses in lungs and patient and also a reduced heart Dmean, while B-VMAT resulted in reduced low-dose spread in lungs and left breast. CONCLUSIONS: Non-coplanar beam configurations were favorable for young female mediastinal lymphoma patients, with patient-specific and plan-parameter-dependent dosimetric advantages of NCP_x≥12 and B-VMAT. Individualization of beam configuration approach, considering also the faster delivery of B-VMAT vs. NCP_x≥12, can importantly improve the treatments.

Fully automated VMAT treatment planning for advanced-stage NSCLC patients.

PURPOSE: To develop a fully automated procedure for multicriterial volumetric modulated arc therapy (VMAT) treatment planning (autoVMAT) for stage III/IV non-small cell lung cancer (NSCLC) patients treated with curative intent. MATERIALS AND METHODS: After configuring the developed autoVMAT system for NSCLC, autoVMAT plans were compared with manually generated clinically delivered intensity-modulated radiotherapy (IMRT) plans for 41 patients. AutoVMAT plans were also compared to manually generated VMAT plans in the absence of time pressure. For 16 patients with reduced planning target volume (PTV) dose prescription in the clinical IMRT plan (to avoid violation of organs at risk tolerances), the potential for dose escalation with autoVMAT was explored. RESULTS: Two physicians evaluated 35/41 autoVMAT plans (85%) as clinically acceptable. Compared to the manually generated IMRT plans, autoVMAT plans showed statistically significant improved PTV coverage (V95% increased by 1.1% ± 1.1%), higher dose conformity (R50 reduced by 12.2% ± 12.7%), and reduced mean lung, heart, and esophagus doses (reductions of 0.9 Gy ± 1.0 Gy, 1.5 Gy ± 1.8 Gy, 3.6 Gy ± 2.8 Gy, respectively, all p < 0.001). To render the six remaining autoVMAT plans clinically acceptable, a dosimetrist needed less than 10 min hands-on time for fine-tuning. AutoVMAT plans were also considered equivalent or better than manually optimized VMAT plans. For 6/16 patients, autoVMAT allowed tumor dose escalation of 5-10 Gy. CONCLUSION: Clinically deliverable, high-quality autoVMAT plans can be generated fully automatically for the vast majority of advanced-stage NSCLC patients. For a subset of patients, autoVMAT allowed for tumor dose escalation.

The CyberKnife radiosurgery system for lung cancer.

The CyberKnife is a frameless image-guided radiotherapy system involving a 6-MV linear accelerator mounted on a robotic arm. The imaging system consists of two diagnostic x-ray sources mounted to the ceiling paired with amorphous silicon detectors to acquire live digital radiographic images of the tumor or tumor surrogates including bony anatomy or implanted fiducial markers. The Synchrony system enables 4D real-time tracking of tumors that move with respiration. Owing to this complex system, moving tumors can be treated with an accuracy of 2 mm or less while patients breathe normally. Clinical results of inoperable patients with peripheral early-stage lung cancer are excellent. The toxicity is low and the treatment does not result in a loss in quality of life.

Radical radiotherapy compared with surgery for advanced squamous cell carcinoma of the base of tongue.

PURPOSE: This study reports on T3/T4 base of tongue (BOT) tumors treated at the Erasmus MC (Rotterdam) with external beam radiotherapy (EBRT) and brachytherapy (BT). Local control, survival, and functional outcome are compared to results obtained in similar patients treated at the Vrije University Medical Center (VUMC, Amsterdam) by surgery and postoperative RT (PORT). METHODS AND MATERIALS: At Rotterdam 46/2 Gy was given to the primary and bilateral neck, followed by an implant using low-dose-rate (LDR 24-35 Gy; median 27 Gy), or fractionated high-dose-rate (fr. HDR 20-28 Gy; median 24 Gy). A neck dissection (ND) was performed in case of N+ disease. 67% of BOT tumors had a T4 cancer. At Amsterdam surgery (S) followed by PORT 40-70 Gy (median 60 Gy) was performed; 26% BOT tumors were T4. Sex, age and nodal distribution were similar. Actuarial local control and survival were computed. Performance Status Scale (PSS) scores were established. Xerostomis was determined on visual analog scales (VAS). RESULTS: Local failure at 5-years was 37% (Rotterdam) vs. 9% (Amsterdam) (p < 0.01). The overall survival was not significantly different (median 2.5 years vs. 2.9 years, respectively [p = 0.47]). The PSS favored brachytherapy. Both groups were equally affected by xerostomia. CONCLUSIONS: The 5-year local control was 65% with EBRT and BT. This result is strongly affected by 4 patients with residual disease after implantation. The Rotterdam patients had more advanced BOT tumors (67% vs. 26% T4), explaining the higher local failure rate. Given the organ preservation properties of radiotherapy-only and the better PSS scores, the jury is still out on the optimal treatment for BOT tumors.

Considerations for post-operative radiotherapy to the hemithorax following extrapleural pneumonectomy in malignant pleural mesothelioma.

With growing interest in evaluating extrapleural pneumonectomy (EPP) and post-operative in selected patients with early stage malignant pleural mesothelioma, it is essential that clinical trials should be conducted using a clear and reproducible radiotherapy protocol. The considerations which have determined the policy of radiotherapy planning and treatment delivery for patients with mesothelioma in The Netherlands are given. As well as general considerations such as patient selection, target volume and critical organ delineation, a dose-fractionation scheme, constraints relating to normal tissue, treatment planning, the type of external beam equipment, treatment verification and radiation toxicity and scoring are all taken into account.

Brachytherapy versus surgery in carcinoma of tonsillar fossa and/or soft palate: late adverse sequelae and performance status: can we be more selective and obtain better tissue sparing?

PURPOSE: To report on the tumor control, adverse late normal tissue sequelae, and functional performance in patients with tonsillar fossa and/or soft palate (SP) tumors. The aim of the study is to validate the use of a more selective clinical target volume in conjunction with highly conformal radiotherapy (RT) techniques to better spare the surrounding normal tissues. METHODS AND MATERIALS: Between 1986 and 2001, T1-T3 tonsillar fossa/SP tumors were treated in the Erasmus Medical Center using external beam radiotherapy (EBRT) to 46 Gy in 2-Gy fractions to the primary tumor and neck, followed by brachytherapy (BT) to the primary. Neck dissection was performed for node-positive disease (BT group; 104 patients). If BT was not feasible, patients underwent surgery and postoperative RT (PORT) to a dose of 50-70 Gy in 2-Gy fractions (surgery group; 86 patients). Local control, regional control, disease-free survival, and overall survival were determined. Late side effects were scored using the Radiation Therapy Oncology Group criteria. Univariate and multivariate Cox regression analyses were performed for regional failure (RF), with the parameters gender, age, site, TN stage, modality, dose, and overall treatment time. Recurrences in the contralateral neck were also related to significant ipsilateral involvement of the base of tongue and/or involvement of the SP crossing the midline. To determine the performance status scale scores and degree of xerostomia, a survey was conducted among patients living with no evidence of disease and a minimum of 2 years of follow-up. For that purpose, a research nurse interviewed patients regarding eating in public, normalcy of diet, normalcy of speech, and xerostomia. RESULTS: The tumor control rates after BT vs. surgery at 5 years were 88% vs. 88% for local control; 93% vs. 85% for regional control; 57% vs. 52% for disease-free survival; 67% vs. 57% for overall survival; and 5% vs. 6% for RF. No patient had RF in the contralateral untreated N0 neck (0 of 14 vs. 0 of 15). Multivariate Cox regression analysis for RF was statistically significant for Stage T2 vs. T3 (hazard ratio 0.09) and for the dose to the neck >46 Gy (hazard ratio, 8.7; 95% confidence interval, 1.3-57.1). The significant late side effects in the BT group vs. surgery group were ulcer in 39% vs. 7% (p = 0.001) and trismus in 1% vs. 21% (p = 0.005). The performance status scale scores and response to questions regarding xerostomia for BT vs. surgery revealed no statistically significant differences for eating in public, normalcy of diet, normalcy of speech, and xerostomia. The mean visual analog score for xerostomia was 5.5 in the BT group vs. 6 in the surgery group. CONCLUSION: Excellent locoregional control was obtained in T1-T3 tonsillar fossa and/or SP tumors. The rate at 10 years was 84% (BT group) vs. 78% (surgery group). However, adverse late side effects were not negligible. In addition to modality-specific side effects (ulcer/trismus), both treatment groups were significantly affected by xerostomia. Only 6 recurrences (4%) were observed in the 149 electively treated contralateral necks, and no relapses were seen in the 29 untreated contralateral necks. We, therefore, suggest that it is not necessary to treat the contralateral neck, unless the tumor extends beyond the midline of the soft palate (uvula) or beyond the lateral one-third of the ipsilateral base of the tongue. Moreover, with the currently available CT-based neck level definitions, more conformal contours (i.e., tighter boundaries) around the clinical target volume can be designed. In this way, critical structures such as the temporomandibular joint and part of the pterygoid muscles can be avoided more easily. Also, when using highly conformal treatment techniques (e.g., intensity-modulated RT), one can further reduce the dose to the major salivary glands and oral mucosa. We believe these measures will lead to less trismus and less xerostomia.