Urs M. Luetolf

Locoregional Failure Analysis in Head-and-Neck Cancer Patients Treated with IMRT

Purpose:Purpose: Analysis of locoregional failure in head-and-neck cancer (HNC) following intensity-modulated radiation therapy (IMRT), with focus on the location of locoregional failures in relation to the chosen planning target volumes (PTVs) and dose distributions.Patients and Methods:Between January 2002 and May 2006, 280 HNC patients were subjected to IMRT at the authors’ institution. Mean follow-up was 23.2 months (3–59.3 months). Definitive IMRT was performed in 75% of all patients. In 71%, simultaneous cisplatin-based chemotherapy was given. 70% of patients presented with T3/4, T1–2 N2c/3 or recurred disease. Locoregional failure patterns were analyzed.Results:2-year local, nodal, distant, disease-free, and overall survival rates were 80%, 87%, 87%, 73%, and 82%, respectively. 46 local (16%) and 31 nodal (11%) failures have been observed so far. Local tumor persistence was seen in 23/46 cases (50%), and nodal persistence in 12/31 (39%), respectively. One marginal local failure developed in a patient referred for a recurred oral cavity tumor. Three nodal failures developed outside the PTVs at unexpected locations. All other failures have been confirmed “in field”. No failure occurred in level Ib or upper level II. Local failure occurred mainly following definitive IMRT for large tumors, nodal failure only in nodally positive patients with nodal high-risk features.Conclusion:The dose-volume concept as used here has shown to be adequate, with disease failure developing at the site of the initial gross tumor manifestation inside the boost volume.Ziel:Analyse des lokoregionalen Tumorversagens nach intensitätsmodulierter Radiotherapie (IMRT), mit Fokus auf den Ort des Versagens in Bezug auf die konturierten Volumina bzw. die Dosisverteilung.Patienten und Methodik:Zwischen Januar 2002 und Mai 2006 wurden an der eigenen radioonkologischen Klinik 280 Patienten mit Kopf-Hals-Tumoren einer IMRT unterzogen. Die mittlere Beobachtungszeit beläuft sich auf 23,2 Monate (3–59,3 Monate). Bei 75% der Patienten wurde eine definitive IMRT durchgeführt. 71% der Patienten erhielten eine simultane Chemotherapie mit Cisplatin. 70% wurden mit fortgeschrittenen Stadien T3/4, T1–2 N2c/3 oder einem Rezidiv zugewiesen (Tabelle 2). Das lokoregionale Ereignismuster wurde analysiert.Ergebnisse:Die Lokal-, Nodal- und Fernkontrollraten nach 2 Jahren beliefen sich auf 80%, 87% und 87%, die krankheitsfreie bzw. Gesamtüberlebensrate betrug 73% und 82% (Tabelle 4). 46 Fälle (16%) lokalen und 31 (11%) nodalen Versagens wurden bislang festgestellt, die in 23/46 Fällen (50%) einer lokalen und in 12/31 Fällen (39%) einer nodalen Tumorpersistenz entsprachen. Nur ein Patient mit einem bereits rezidivierten Mundhöhlentumor entwickelte ein Feldrandrezidiv (Tabelle 1). Dreimal fand sich ein nodales Versagen außerhalb der Planungszielvolumina an unerwarteten Lokalisationen. Alle anderen Fälle von Versagen konnten als „im Feld“ befindlich bestätigt werden. Kein Versagen wurde im Lymphknotenlevel I oder kranial im Level II gefunden (Tabellen 5 und 6). Lokales Versagen erfolgte hauptsächlich bei primär bestrahlten Patienten mit großem Tumorvolumen (Abbildungen 1 und 2a); nodales Versagen fand sich ausschließlich bei initial nodal positiven Patienten mit nodalen Risikofaktoren (Tabelle 3, Abbildung 2b).Schlussfolgerung:Das hier verwendete Dosis-Volumen-Konzept erwies sich als adäquat, da der Großteil der Rückfälle am Ort der initialen Tumormanifestation, innerhalb des Boostvolumens, auftrat.

The impact of radiotherapy in the treatment of desmoid tumours. An international survey of 110 patients. A study of the Rare Cancer Network

PurposeA multi-centre study to assess the value of combined surgical resection and radiotherapy for the treatment of desmoid tumours.Patients and methodsOne hundred and ten patients from several European countries qualified for this study. Pathology slides of all patients were reviewed by an independent pathologist. Sixty-eight patients received post-operative radiotherapy and 42 surgery only. Median follow-up was 6 years (1 to 44). The progression-free survival time (PFS) and prognostic factors were analysed.ResultsThe combined treatment with radiotherapy showed a significantly longer progression-free survival than surgical resection alone (p smaller than 0.001). Extremities could be preserved in all patients treated with combined surgery and radiotherapy for tumours located in the limb, whereas amputation was necessary for 23% of patients treated with surgery alone. A comparison of PFS for tumour locations proved the abdominal wall to be a positive prognostic factor and a localization in the extremities to be a negative prognostic factor. Additional irradiation, a fraction size larger than or equal to 2 Gy and a total dose larger than 50 Gy to the tumour were found to be positive prognostic factors with a significantly lower risk for a recurrence in the univariate analysis. This analysis revealed radiotherapy at recurrence as a significantly worse prognostic factor compared with adjuvant radiotherapy. The addition of radiotherapy to the treatment concept was a positive prognostic factor in the multivariate analysis.ConclusionPostoperative radiotherapy significantly improved the PFS compared to surgery alone. Therefore it should always be considered after a non-radical tumour resection and should be given preferably in an adjuvant setting. It is effective in limb preservation and for preserving the function of joints in situations where surgery alone would result in deficits, which is especially important in young patients.

Postoperative IMRT in head and neck cancer

BackgroundAim of this work was to assess loco-regional disease control in head and neck cancer (HNC) patients treated with postoperative intensity modulated radiation therapy (pIMRT). For comparative purposes, risk features of our series have been analysed with respect to histopathologic adverse factors. Results were compared with an own historic conventional radiation (3DCRT) series, and with 3DCRT and pIMRT data from other centres.Between January 2002 and August 2006, 71 patients were consecutively treated with pIMRT for a squamous cell carcinoma (SCC) of the oropharynx (32), oral cavity (22), hypopharynx (7), larynx (6), paranasal sinus (3), and an unknown primary, respectively. Mean and median follow up was 19 months (2–48), and 17.6 months. 83% were treated with IMRT-chemotherapy. Mean prescribed dose was 66.3 Gy (60–70), delivered with doses per fraction of 2–2.3 Gy, respectively.Results2-year local, nodal, and distant control rates were 95%, 91%, and 96%, disease free and overall survival 90% and 83%, respectively. The corresponding survival rates for the subgroup of patients with a follow up time >12 months (n = 43) were 98%, 95%, 98%, 93%, and 88%, respectively. Distribution according to histopathologic risk features revealed 15% and 85% patients with intermediate and high risk, respectively. All loco-regional events occurred in the high risk subgroup.ConclusionSurgery followed by postoperative IMRT in patients with substantial risk for recurrence resulted in high loco-regional tumor control rates compared with large prospective 3DCRT trials.

The use of a leg holder immobilisation device in 3D-conformal radiation therapy of prostate cancer.

BACKGROUND AND PURPOSE To evaluate the impact of a leg holder immobilisation device on patient positioning accuracy in the treatment of prostate cancer. MATERIAL AND METHODS Twenty patients of similar age and stage of disease treated with curative external beam radiotherapy for prostate cancer were included prospectively. Ten patients were sequentially allocated to one of the two groups, and treated either with or without a leg holder. Treatment set-up alignment accuracy was assessed with an electronic portal imaging device (EPID). RESULTS Set-up accuracy was 0.3, 0.3 and 0.2 cm for patients with a leg holder, and 0.3, 0.4 and 0.2 cm for patients without a leg holder in the cranio-caudal, anterior-posterior and in the lateral positions, respectively. The difference is not significant. The repositioning accuracy of combined (sagittal and lateral) in-plane rotations on the other hand, was significantly improved with a leg holder device (P = 0.04). CONCLUSIONS Set-up accuracy can be improved using a leg holder immobilisation device in terms of rotational movement accuracy, thus making on-line corrections more accurate using EPID in the treatment of prostate cancer.

Letter by G. Studer, U. M. Luetolf, C. Glanzmann on the comment by H. Christiansen & C. F. Hess. Locoregional failure analysis in head and neck cancer patients treated with IMRT.

We would like to reply on the comment by Christiansen & Hess [1] on our article “Locoregional failure analysis in head and neck cancer patients treated with IMRT” [3] in Strahlenther Onkol 2007;183:417–25 (No. 8). The authors state that our study results do considerably modify the widely accepted clinical target volume (CTV) definitions for head and neck cancer (HNC) published by Gregoire et al. [2]. This statement requires some precision, as Gregoire et al. did not recommend CTVs related to specific HNC situations, but offered a highly appreciated anatomic image atlas of the relevant lymph node regions in HNC, which per se are well known for decades (original article, p. 234, under “6. Discussion”: “These guidelines do not intend to give any recommendations for the optimal treatment strategy for node negative patients with a head neck primary, or the selection of various levels that require treatment”). As described in our methods, we are somewhat more restrictive in the elective irradiation of node negative neck sides, compared to the recommendations of many RTOG protocols, e.g., with respect to the upper level II (often not going up to the skull base on the noninvolved neck side), or the medial retropharyngeal node groups, or regarding the submandibular groups in many patients with other than oral cavity tumors, respectively. However, results of a recent update of our intensity modulated radiotherapy (IMRT) cohort of meanwhile 410 curatively irradiated patients (01/2002–04/2007) confirm the appropriateness of chosen planning target volumes (PTVs), as no nodal relapses developed in initially noninvolved lymphatic areas, and no additional failures out of boost areas developed in the meantime. Unfortunately, the authors do not give any information about their own practice of IMRT PTV/CTV and treatment schedules. The authors state, that the follow-up time of 2 years is too short. In concordance with many published reports in the literature, our updated results again confirm a 2 year follow-up time being long enough to draw reliable conclusions in HNC, as only two out of 89 events occurred later than 2 years post IMRT (Figure 1). Concerning the other points issued by Christiansen & Hess, combined chemotherapy should be considered the standard treatment in HNC today. Slight dose escalation using simultaneously integrated boost (SIB) IMRT is recently under investigation in a prospective study set up at our institution (started spring 2007). Dose escalation and variation of the fractionation regimen have to be performed very carefully: