B. Prevost

Image-Guided Robotic Stereotactic Radiation Therapy with Fiducial-Free Tumor Tracking for Lung Cancer

PurposeStereotactic body radiation therapy (SBRT) for early-stage lung cancer can be achieved with several methods: respiratory gating, body frame, or real-time target and motion tracking. Two target tracking methods are currently available with the CyberKnife® System: the first one, fiducial tracking, requires the use of radio-opaque markers implanted near or inside the tumor, while the other, Xsight® Lung Tracking System, (XLTS) is fiducial-free. With XLTS, targeting is synchronized directly with target motion, which occurs due to respiration. While the former method (fiducial tracking) is well documented, the clinical relevance of the latter (tracking without fiducials) has never been well described to this date.Patients and MethodsA study was performed at our department for each patient treated for lung cancer with CyberKnife using XLTS. Selection criteria were: primary or recurring T1 or T2 stage non-small-cell lung cancer (NSCLC) with 15–60 mm tumor size. Initial staging included CT-Scan and FDG-PET.ResultsFifty-one patients not amenable to surgery were treated with XLTS. Median follow-up was 15 months (range, 5–30 months). Median tumor size was 24 mm (range, 15–60 mm). Median total dose was 60 Gy (36–60 Gy) in three fractions. Actuarial overall survival was 85.5% (95% CI = 74.5–96%) at 1 year and 79.4% (95% CI = 64–94.8%) at 2 years. Actuarial local control rate was 92% (95% CI = 84–99%) at one1 year and 86% (95% CI = 75–97%) at 2 years.ConclusionLocal control and overall survival rates were similar to previous reports that used fiducials for tumor tracking. Toxicity was lower than most studies since tumor tracking did not require fiducial implantion. This fiducial-free method for respiratory motion tracking is a valid option for the most fragile patients.

A single-institution study of stereotactic body radiotherapy for patients with unresectable visceral pulmonary or hepatic oligometastases

PurposeThe purpose of this study is to evaluate the feasibility, efficacy and toxicity of SBRT for treatment of unresectable hepatic or lung metastases regardless of their primary tumor site for patients who received prior systemic chemotherapy.Methods and materialsBetween July 2007 and June 2010, 90 patients were treated with the CyberKnife® SBRT system for hepatic or pulmonary metastatic lesions. Medical records were retrospectively reviewed. The endpoints of this study were local control, overall survival (OS), disease-free survival (DFS), local relapse free-survival (LRFS), and treatment toxicity.ResultsA total of 113 liver and 26 lung metastatic lesions in 52 men (58%) and 38 women (42%) were treated. Median follow-up was 17 months. Median age at treatment was 65 years (range, 23–84 years). Primary cancers were 63 GI, three lung, eight breast, four melanoma, three neuro-endocrine tumors, and three sarcomas. Median diameter of the lesions was 28 mm (range, 7–110 mm) for liver and 12.5 mm (range, 5–63.5 mm) for lung. Local control rates at 1 and 2 years were 84.5% and 66.1%, respectively. Two-year overall survival rate was 70% (95% CI: 55–81%). The 1 and 2-year disease-free survival rates were 27% (95% CI: 18–37%) and 10% (95% CI: 4–20%), respectively. Median duration of disease-free survival was 6.7 months (95% CI: 5.1–9.5 months). Observed toxicities included grade 1–3 acute toxicities. One grade 3 and no grade 4 toxicity were reported.ConclusionHigh-dose SBRT for metastatic lesions is both feasible and effective with high local control rates. Overall survival is comparable with other available techniques. Treatment is well tolerated with low toxicity rates. It could represent an interesting treatment option for oligometastatic patients not amenable to surgery, even when patients had been pre-treated with chemotherapy.SummaryStereotactic body radiotherapy (SBRT) has previously been successfully used in the treatment of metastatic lesions. It could be considered as a curative option for oligometastatic patients. This retrospective study involved 90 patients, designed to test potential effectiveness of SBRT in the treatment of oligometastases irrespective of primary. Results suggest SBRT could be an effective treatment extending patients’ life span. This treatment appears to be more effective when used prior to multiple systemic treatment regimens.

CONCOMITANT B.I.D. RADIOTHERAPY AND CHEMOTHERAPY WITH CISPLATIN AND 5-FLUOROURACIL IN UNRESECTABLE SQUAMOUS-CELL CARCINOMA OF THE PHARYNX: CLINICAL AND PHARMACOLOGICAL DATA OF A FRENCH MULTICENTER PHASE II STUDY

PURPOSE The aim of this phase II study conducted on unresectable squamous cell carcinoma (USCC) of the oro- and hypopharynx was to associate twice-a-day (b.i.d.) continuous nonaccelerated radiotherapy with concomitant cisplatin (CP)-5-fluorouracil (5-FU) chemotherapy, both given at full dose. Feasibility, efficacy, survival, and pharmacokinetic-pharmacodynamic relationships were analyzed. METHODS AND MATERIALS Fifty-four consecutive patients with strictly USCC of oro- and/or hypopharynx received continuous b.i.d. radiotherapy (RT) (2 daily fractions of 1.2 Gy, 5 days a week, with a 6-h minimal interval between fractions). Total RT dose was 80.4 Gy on the oropharynx and 75.6 Gy on the hypopharynx. Three chemotherapy (CT) courses of CP-5-FU were given during RT at 21-day intervals (third not delivered after the end of RT). CP dose was 100 mg/m2 (day 1) and 5-FU was given as 5-day continuous infusion (day 2-day 6: 750 mg/m2/day cycle 1, 750 mg total dose/day cycle 2 and 3). Pharmacokinetics was performed for 5-FU (105 h follow-up) and CP (single sample at 16 h). Special attention was paid to supportive care. RESULTS Good feasibility of RT was observed (85.2% of patients with total dose > 75 Gy). Five patients received 1 CT cycle, 34: 2 cycles, and 15: 3 cycles. The most frequent and severe acute toxicities were mucositis with grade 3-4 occurring in 28% at cycle 1 and 86% at cycle 2, as well as neutropenia (43% at cycle 2). Locoregional control at 6 months was observed in 66.7% of patients. No late toxicity above grade 2 RTOG was noticed. CP dose and 5-FU AUC(0-105h) were significantly linked to grade 3-4 neutropenia (cycle 2). Cumulative total platinum (Pt) concentration and Karnofsky index were the only independent predictors of locoregional control at 6 months. Finally, total RT dose and total Pt concentration were the only independent predictors of specific survival. CONCLUSION This protocol showed good locoregional response with an acceptable toxicity profile. Pharmacokinetic survey is probably an effective approach to further reduce toxicity and improve efficacy. A multicentric randomized phase III study, now underway, should confirm these encouraging results.

Extracranial Stereotactic Radiotherapy: Preliminary Results with the CyberKnife®

In the field of radiation oncology, equipment for fractionated radiotherapy and single-dose radiosurgery has become increasingly accurate, together with the introduction of robotized treatments. A robot is a device that can be programmed to carry out accurate, repeated and ad-justed tasks in a given environment. Treatment of extracranial lesions involves taking into account organ mobility (tumor and healthy tissue) whilst retaining the ability to stereotactically locate the target. New imaging techniques (single-photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), positron emission tomography (PET)) provide further relevant information to slice images (computed tomography (CT) scans, MRI) for target definition. Hypo-fractionated treatments can only be used for curative treatment if the target is accurately defined and tracked during treatment. The CyberKnife® is a non-invasive system of radiosurgery and fractionated stereotactic radiotherapy. For intracranial lesions treated by single-dose radiosurgery, it has been used to treat meningioma, acoustic neuromas, pituitary adenoma, metastases, arteriovenous malformations and refractory pain (trigeminal neuralgia). More than 10,000 patients have been treated worldwide. Currently, the most significant developments are in the field of extracranial stereotactic radiotherapy (lung, liver, reirradiation, prostate, etc.). Clinical results obtained in the Cyberknife Nord-Ouest program after 1 year of experience are presented.

HIGH-DOSE-RATE BRACHYTHERAPY FOR NON-SMALL-CELL LUNG CARCINOMA: A RETROSPECTIVE STUDY OF 226 PATIENTS

PURPOSE To evaluate the efficacy and toxicity of high-dose-rate (HDR) brachytherapy in patients with inoperable endobronchial carcinoma. METHODS AND MATERIALS We retrospectively reviewed the records (April 1991-May 2004) of patients with non-small-cell carcinoma, with no extrabronchial spread on computed tomography scans, who underwent HDR brachytherapy because of contraindications to surgery and external beam radiation therapy. Kaplan-Meier survival curves were compared by the log-rank test. Prognostic factors were analyzed by multivariate analysis. RESULTS 226 patients (223 men, 3 women, mean age: 62.2 years (range, 40-84)) were included. Of those, 217 (97%) had squamous cell carcinoma (Tis/T1/T2/Tx: 60/153/9/4). Dose was prescribed at 1 cm from the radius (24-35 Gy in 4-6 fractions). Mean follow-up was 30.4 months (range, 9-116). Complete endoscopic response rate was 93.6% at 3 months. One hundred twenty-eight patients (56%) died of intercurrent disease (n = 45), local failure (n = 36), metastasis (n = 10), local failure and metastasis (n = 11), complications (n = 13), and other causes (n = 12). The 2-year and 5-year survival rates were, respectively, 57% and 29% (overall) (median, 28.6 months), 81% and 56% (cancer-specific), and 68% and 50% (local disease-free). Acute toxicity included pneumothorax (1.5%) and mucosal inflammation (10%). Late complications were hemoptysis (6.6% with 5% of fatalities), bronchitis (19.5%), and necrosis (3.5%). In multivariate analysis, a distal tumor location and the use of two catheters were associated with improved local disease-free survival (p = 0.003 and p = 0.007, respectively) and a distal tumor location with improved overall survival (p = 0.0001). CONCLUSIONS This large retrospective study confirms that HDR brachytherapy is an efficient and safe treatment in patients with inoperable endobronchial carcinoma.

Management of early oral cavity cancer. Experience of Centre Oscar Lambret

From 1974 to 1983, 579 patients presenting with early oral cancer (excluding lip tumours) were treated at Centre Oscar Lambret. Of these, 429 were treated locally by brachytherapy with local control achieved in 82% of the cases (90% after salvage surgery). Treatment-related complications occurred in 19% of the cases, requiring surgical management in 13 patients. In contrast, only 51% of the 35 patients treated by external radiotherapy and brachytherapy were controlled, resulting in a poor 5-year survival (14%). Results for the 24 patients treated surgically were similar to those of brachytherapy alone. Finally, for T1 T2 N0 patients, the advantages of an elective neck dissection are not clear and could be clarified by a randomised trial. Indeed, this retrospective study failed to find a significant difference in the incidence of death due to an uncontrolled neck evolution whatever the neck management.

Radiothérapie stéréotaxique de carcinomes bronchiques primitifs: suivi non invasif de la cible en temps réel

PURPOSE Stereotactic radiation therapy using the CyberKnife(®) has been introduced in France in 2006. Two treatment modalities are currently available: the first one (Synchrony(®)) is a real-time fiducial-based target tracking system, while the other (Xsight Lung Tracking [XLT] System(®)) is completely fiducial-free. PATIENTS AND METHODS Sixty-eight patients were treated for a pulmonary tumor between June 2007 and November 2009. Since august 2008, the XLT System(®) was used for 26 patients. We report the necessary conditions for the XLT System (position, laterality and size of the tumor), the toxicity and outcome of this treatment. RESULTS Twenty-two patients were analyzed. Median follow-up was 6 months (min=3; max=16). Local control rate was 100%. The main toxicity was grade grade 1 pulmonary alveolitis (27%). No grade 3 or 4 toxicities were reported. CONCLUSION The high local control rate and low toxicity obtained with the CyberKnife(®) XLT System(®) suggest that such treatment is an alternative for inoperable patients.

Utilisation d'un système d'imagerie en temps réel dans le contrôle quotidien de patients traités par irradiation pour un cancer thoracique

PURPOSE: Retrospective analysis of the results obtained with daily interactive use of portal imaging for monitoring thoracic cancer radiotherapy. MATERIALS AND METHODS: A Siemens electronic portal imaging system called Beamviewplus was used daily in 15 lung cancer patients for each X-ray field. Out of the 714 expected portal images, 585 (82%), were obtained and printed. RESULTS: We counted 94 errors in the 585 successful controls (16%). Four main classes of errors were identified: irradiation field placement (47 cases, 50%), shielding placement (30 cases, 32%) patients position on the till examining table (14 cases, 15%), and selection of the energy (3 cases, 3%). Forty percent of these errors were potentially serious in terms of treatment volume and vital organ protection. CONCLUSION: Only portal imaging control could easily detect errors because they occurred randomly. We thus consider the use of this daily system helpful for patient management.

CT appearance of pulmonary carcinomas after stereotactic radiation therapy.

Stereotactic radiation therapy (SRT) is becoming more and more important in the treatment of inoperable patients with early stages of pulmonary carcinomas (T1-T2 N0M0). In certain cases, evaluation of the response is still problematical and it can be difficult to differentiate response from progression. The aim of this paper is to set out these various changes and to produce a protocol for optimal monitoring. By comparing our clinical experience with data from the literature, the main visual aspects on a CT scan are set out and illustrated for each clinical situation: radiation pneumonitis, radiation fibrosis, therapeutic response and progression. The literature was reviewed by querying the main databases and selecting papers concerning pulmonary SRT and post-therapeutic radiological appearance. CT appearance induced by SRT differs significantly from images after classic conformal radiation therapy, both morphologically and chronologically. In particular, the modifications induced by stereotactic radiation therapy are only seen in a limited volume surrounding the volume treated. Knowledge of the radiological criteria necessary to differentiate between a therapeutic response and recurrence is of major importance in the present context of increase in use of this technique.

Results and special considerations when treating elderly patients with CyberKnife ® : A review of 345 cases

The relatively recent introduction of CyberKnife® in the field of radiotherapy has prompted the question of accessibility and usefulness of this technique for seniors. From June 2007 to June 2009, we treated 345 patients of all ages with CyberKnife as part of a single-center study. Median age was 61 years (range, 8-86 years). Ninety-eight patients were over 70 and 17 were older than 80. The treatment could not be completed with 2% (2/98) patients over 70 vs. 3.6% (9/247) among the younger (ns). Physiologic or psychologic problems in maintaining position for a long time were not more frequent among those over 70. The same was true with those over 80. Patients over 70 years old are able to tolerate CyberKnife treatment as efficiently as their younger counterparts. Elderly patients should not be restricted from access to CyberKnife radiosurgery with curative intent.