Outcome and patterns of failure after postoperative intensity modulated radiotherapy for locally advanced or high-risk oral cavity squamous cell carcinoma

Background To determine the outcome and patterns of failure in oral cavity cancer (OCC) patients after postoperative intensity modulated radiotherapy (IMRT) with concomitant systemic therapy. Methods All patients with locally advanced (AJCC stage III/IV) or high-risk OCC (AJCC stage II) who underwent postoperative IMRT at our institution between December 2006 and July 2010 were retrospectively analyzed. The primary endpoint was locoregional recurrence-free survival (LRRFS). Secondary endpoints included distant metastasis-free survival (DMFS), overall survival (OS), acute and late toxicities. Results Overall 53 patients were analyzed. Twenty-three patients (43%) underwent concomitant chemotherapy with cisplatin, two patients with carboplatin (4%) and four patients were treated with the monoclonal antibody cetuximab (8%). At a median follow-up of 2.3 (range, 1.1–4.6) years the 3-year LRRFS, DMFS and OS estimates were 79%, 90%, and 73% respectively. Twelve patients experienced a locoregional recurrence. Eight patients, 5 of which had both a flap reconstruction and extracapsular extension (ECE), showed an unusual multifocal pattern of recurrence. Ten locoregional recurrences occurred marginally or outside of the high-risk target volumes. Acute toxicity grades of 2 (27%) and 3 (66%) and late toxicity grades of 2 (34%) and 3 (11%) were observed. Conclusion LRRFS after postoperative IMRT is satisfying and toxicity is acceptable. The majority of locoregional recurrences occurred marginally or outside of the high-risk target volumes. Improvement of high-risk target volume definition especially in patients with flap reconstruction and ECE might transfer into better locoregional control

Definitive intensity modulated radiotherapy in locally advanced hypopharygeal and laryngeal squamous cell carcinoma: mature treatment results and patterns of locoregional failure.

PurposeTo assess clinical outcomes and patterns of loco-regional failure (LRF) in relation to clinical target volumes (CTV) in patients with locally advanced hypopharyngeal and laryngeal squamous cell carcinoma (HL-SCC) treated with definitive intensity modulated radiotherapy (IMRT) and concurrent systemic therapy.MethodsData from HL-SCC patients treated from 2007 to 2010 were retrospectively evaluated. Primary endpoint was loco-regional control (LRC). Secondary endpoints included local (LC) and regional (RC) controls, distant metastasis free survival (DMFS), laryngectomy free survival (LFS), overall survival (OS), and acute and late toxicities. Time-to-event endpoints were estimated using Kaplan-Meier method, and univariate and multivariate analyses were performed using Cox proportional hazards models. Recurrent gross tumor volume (RTV) on post-treatment diagnostic imaging was analyzed in relation to corresponding CTV (in-volume, > 95% of RTV inside CTV; marginal, 20¿95% inside CTV; out-volume, < 20% inside CTV).ResultsFifty patients (stage III: 14, IVa: 33, IVb: 3) completed treatment and were included in the analysis (median follow-up of 4.2 years). Three-year LRC, DMFS and overall survival (OS) were 77%, 96% and 63%, respectively. Grade 2 and 3 acute toxicity were 38% and 62%, respectively; grade 2 and 3 late toxicity were 23% and 15%, respectively. We identified 10 patients with LRF (8 local, 1 regional, 1 local¿+¿regional). Six out of 10 RTVs were fully included in both elective and high-dose CTVs, and 4 RTVs were marginal to the high-dose CTVs.ConclusionThe treatment of locally advanced HL-SCC with definitive IMRT and concurrent systemic therapy provides good LRC rates with acceptable toxicity profile. Nevertheless, the analysis of LRFs in relation to CTVs showed in-volume relapses to be the major mode of recurrence indicating that novel strategies to overcome radioresistance are required

Verbesserte VMAT-Planung für Kopf- und Halstumore mit einem fortschrittlichen Optimierungs-Algorithmus

OBJECTIVE In this study, the "Progressive Resolution Optimizer PRO3" (Varian Medical Systems) is compared to the previous version "PRO2" with respect to its potential to improve dose sparing to the organs at risk (OAR) and dose coverage of the PTV for head and neck cancer patients. MATERIALS AND METHODS For eight head and neck cancer patients, volumetric modulated arc therapy (VMAT) treatment plans were generated in this study. All cases have 2-3 phases and the total prescribed dose (PD) was 60-72Gy in the PTV. The study is mainly focused on the phase 1 plans, which all have an identical PD of 54Gy, and complex PTV structures with an overlap to the parotids. Optimization was performed based on planning objectives for the PTV according to ICRU83, and with minimal dose to spinal cord, and parotids outside PTV. In order to assess the quality of the optimization algorithms, an identical set of constraints was used for both, PRO2 and PRO3. The resulting treatment plans were investigated with respect to dose distribution based on the analysis of the dose volume histograms. RESULTS For the phase 1 plans (PD=54Gy) the near maximum dose D2% of the spinal cord, could be minimized to 22±5 Gy with PRO3, as compared to 32±12Gy with PRO2, averaged for all patients. The mean dose to the parotids was also lower in PRO3 plans compared to PRO2, but the differences were less pronounced. A PTV coverage of V95%=97±1% could be reached with PRO3, as compared to 86±5% with PRO2. In clinical routine, these PRO2 plans would require modifications to obtain better PTV coverage at the cost of higher OAR doses. CONCLUSION A comparison between PRO3 and PRO2 optimization algorithms was performed for eight head and neck cancer patients. In general, the quality of VMAT plans for head and neck patients are improved with PRO3 as compared to PRO2. The dose to OARs can be reduced significantly, especially for the spinal cord. These reductions are achieved with better PTV coverage as compared to PRO2. The improved spinal cord sparing offers new opportunities for all types of paraspinal tumors and for re-irradiation of recurrent tumors or second malignancies.Zielsetzung In dieser Studie wird der „Progressive Resolution Optimizer PRO3“ (Varian Medical Systems) mit der Vorgängerversion „PRO2“ gezielt auf sein Potential bei Kopf-Hals-Tumoren untersucht. Im Vordergrund stehen die Dosisabdeckung des PTV und die Schonung der Risikoorgane (OAR). Methoden Für acht Patienten wurden VMAT-Pläne mit beiden Algorithmen erstellt. Die Gesamtdosis im PTV von 60-72 Gy ist in allen Fällen auf 2-3 Phasen verteilt, die nacheinander abgestrahlt werden. Die Studie ist fokussiert auf die erste Bestrahlungsphase, die in allen Fällen eine komplexe PTV-Struktur mit Planungsdosis von 54 Gy hatte und teilweise mit den Parotiden überlappte. Grundlage für die Optimierung sind die ICRU83-Richtlinien für das PTV und das Planungsziel, das Rückenmark und die Parotiden außerhalb des PTV maximal zu schonen. In einem ersten Schritt wurde durch interaktive Planung mit PRO3 ein möglichst optimaler Plan generiert. Die dabei gewählten Grenzwerte („dose constraints“) für PTV und Risikoorgane wurden in einem zweiten Schritt für den Vergleich der Optimierungsalgorithmen verwendet. Die Optimierung wurde also für diese nun fest vorgegebenen Dosisgrenzwerte sowohl mit PRO3 wiederholt als auch mit PRO2 durchgeführt, ohne zusätzliche Interaktion des Planers. Die resultierenden beiden Bestrahlungspläne wurden anhand der Dosis-Volumen-Histogramme verglichen. Ergebnisse Ein markanter Unterschied in Planqualität ergibt sich aus dem Vergleich der Rückenmarkdosis in der ersten Bestrahlungsphase mit 54 Gy Dosis im PTV. Die maximum-nahe Dosis D2% im Rückenmark konnte mit PRO3 auf 22±5 Gy reduziert werden, während die Optimierung mit identischen Randbedingungen bei PRO2 eine Dosis D2% von 32±12 Gy ergab. Auch die mittlere Dosis für die Parotiden war kleiner mit PRO3, allerdings mit einem weniger großen Unterschied. Eine PTV-Abdeckung von V95% = 97±1% konnte mit PRO3 erreicht werden. Mit PRO2 lag diese Abdeckung dagegen nur bei V95% = 86±5%. Die Mehrzahl der so generierten PRO2-Pläne würde in klinischer Routine nicht akzeptiert und müsste durch die Anpassung der Randbedingungen modifiziert werden, so dass die Dosis auf die Risikoorgane entsprechend höher wird. Schlussfolgerung Ein Vergleich der Optimierungsalgorithmen PRO2 und PRO3 wurde bei acht Patienten mit Kopf-Hals-Tumoren durchgeführt. Hierbei wurde mit dem Algorithmus PRO3 eine deutlich bessere Planqualität erzielt als mit PRO2. Die Verbesserung führt zu einer tieferen Belastung der Risikoorgane, mit dem deutlichsten Unterschied beim Rückenmark. Diese Schonung geht nicht zu Lasten der PTV-Abdeckung. Vielmehr wurde bei allen PRO3-Plänen eine bessere PTV-Abdeckung erzielt als mit PRO2. Die verbesserte Möglichkeit der Rückenmarkschonung, auch für komplexe PTV, eröffnet neue Möglichkeiten der Bestrahlung paraspinaler Tumore. Durch die Schonung des Rückenmarks ist zudem eine erneute Bestrahlung bei wiederauftretenden Tumoren möglich

Therapy options and long-term results of sinonasal malignancies

Nasal and paranasal sinus malignancies are rare. The most common lesions are located in the nasal cavity and the maxillary sinus, although they also occur in the ethmoid, sphenoid and frontal sinuses. Treatment often combines surgery, radiotherapy and chemotherapy. Endoscopic surgical approaches are increasingly used in order to reduce the morbidity associated with standard open resection. The aim of our study was to analyse the long-term treatment results of sinonasal malignancies (SNM), with a special focus on surgical approaches

Outcome and patterns of failure after postoperative intensity modulated radiotherapy for locally advanced or high-risk oral cavity squamous cell carcinoma

Abstract Background To determine the outcome and patterns of failure in oral cavity cancer (OCC) patients after postoperative intensity modulated radiotherapy (IMRT) with concomitant systemic therapy. Methods All patients with locally advanced (AJCC stage III/IV) or high-risk OCC (AJCC stage II) who underwent postoperative IMRT at our institution between December 2006 and July 2010 were retrospectively analyzed. The primary endpoint was locoregional recurrence-free survival (LRRFS). Secondary endpoints included distant metastasis-free survival (DMFS), overall survival (OS), acute and late toxicities. Results Overall 53 patients were analyzed. Twenty-three patients (43%) underwent concomitant chemotherapy with cisplatin, two patients with carboplatin (4%) and four patients were treated with the monoclonal antibody cetuximab (8%). At a median follow-up of 2.3 (range, 1.1–4.6) years the 3-year LRRFS, DMFS and OS estimates were 79%, 90%, and 73% respectively. Twelve patients experienced a locoregional recurrence. Eight patients, 5 of which had both a flap reconstruction and extracapsular extension (ECE), showed an unusual multifocal pattern of recurrence. Ten locoregional recurrences occurred marginally or outside of the high-risk target volumes. Acute toxicity grades of 2 (27%) and 3 (66%) and late toxicity grades of 2 (34%) and 3 (11%) were observed. Conclusion LRRFS after postoperative IMRT is satisfying and toxicity is acceptable. The majority of locoregional recurrences occurred marginally or outside of the high-risk target volumes. Improvement of high-risk target volume definition especially in patients with flap reconstruction and ECE might transfer into better locoregional control.</p

Intensity-modulated radiotherapy for a rendu-osler-weber disease patient with recurrent severe epistaxis: a case report

We present a case of a Rendu-Osler-Weber disease patient with recurrent life threatening epistaxis demanding multiple blood transfusions despite of repetitive endoscopic laser and electrocoagulations, endovascular embolisation, septodermoplasty, and long-term intranasal dressings. As alternative treatment modalities repeatedly failed and the patient became almost permanently dependent on nasal dressing, we performed a highly conformal intensity-modulated radiotherapy of the nasal cavity; a total dose of 50 Gy in 2 Gy single fractions was applied. The therapy was very well tolerated, no acute toxicities occurred. Two weeks after the last radiation dose had been applied, the nasal dressing could be removed without problems. Endoscopical control revealed an almost avascular white mucosa without any trace of bleeding spots; previously existing hemangiomas and crusts had disappeared. After a 1-year-follow up, the patient had no significant recurrent epistaxis

Volumetric regression ratio of the primary tumor and metastatic lymph nodes after induction chemotherapy predicts overall survival in head and neck squamous cell carcinoma: a retrospective analysis.

PURPOSE We looked for any predictive value of change in primary tumor and metastatic lymph node volumes after induction chemotherapy (IC) on oncologic outcome in head and neck squamous cell carcinoma (HNSCC). METHODS Nineteen patients with stage IVA/B HNSCC treated between 2004 and 2010 with at least one cycle of IC (docetaxel, cisplatin and 5-fluorouracil/TPF) and concomitant chemoradiotherapy (CRT) with cisplatin were retrospectively analyzed. Volumes were calculated separately for primary tumor (Vtm), lymph node metastases (Vln) and their sum (Vsum) on computed tomography (CT) images before and after IC. The effect of volumetric changes on locoregional failure (LRF), distant metastasis (DM) and overall survival (OS) was assessed. P values <0.05 were considered as statistically significant. RESULTS The median follow-up of surviving patients was 25 months (range: 10.7-83.3). The median number of cycles and duration of TPF was 3 (range: 1-4) and 44 days (range: 4-116), respectively. Empirical area under the curve (AUC) analyses for death, LRF and DM revealed optimal cut-off values of Vtm diminution (30.54%, AUC: 87%) and Vsum decrease (35.45%, AUC: 64.55%) only for OS (p <0.05). Among those, a reduction in Vsum more than 35.4% between pre- and post-IC was significantly correlated with better OS (100 vs 43% at 2 years, p <0.05). CONCLUSION Volumetric shrinkage of the tumor load after IC assessed with CT seems to predict OS. The assessment of volumetric shrinkage upon IC might be used to decide whether to offer patients alternative strategies like palliative/de-intensified treatments or more aggressive combined modalities after IC