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.

Up-front neck dissection followed by definitive (chemo)-radiotherapy in head and neck squamous cell carcinoma: Rationale, complications, toxicity rates, and oncological outcomes - A systematic review.

BACKGROUND AND PURPOSE: Lymph node metastases of head and neck cancer are considered one of the most negative prognostic factors. While outcomes and feasibility of chemo-radiotherapy ((C)RT) with or without adjuvant planned neck dissection (ND) in organ-preservation treatment strategy have been addressed, the role of ND before (C)RT, called up-front neck dissection (UFND), is not clearly established. This review provides a critical appraisal of UFND. MATERIAL AND METHODS: Articles were identified with a systematic approach. Outcomes included post-UFND delay of (C)RT, surgical complications, radiation toxicity and oncologic outcome. RESULTS: Fifteen studies met inclusion criteria, totaling 607 patients undergoing UFND. Part of the data suggest advantages toward less surgical complications compared with salvage ND, decreased serious acute radiation toxicity and better oncological outcomes when compared with (C)RT alone. The overall heterogeneity of the analyzed data does not allow a meta-analysis that provides high-quality evidence in favor or against UFND. CONCLUSIONS: Due to lack of well-designed randomized trials, it is difficult to assess the role of UFND in organ-preserving (C)RT setting of head and neck cancer.

Outcomes in Advanced Head and Neck Cancer Treated with Up-front Neck Dissection prior to (Chemo)Radiotherapy.

OBJECTIVE: Our aim was to compare outcomes with and without up-front neck dissection prior to (chemo)radiotherapy in head and neck squamous cell carcinoma. STUDY DESIGN: Case series with chart review. SETTING: Tertiary referral center. SUBJECTS AND METHODS: Outcomes of oropharyngeal, laryngeal, and hypopharyngeal squamous cell carcinoma cases with neck lymph node metastases treated from January 2001 to March 2012 were analyzed. Due to imbalances in baseline characteristics between groups treated with (n = 129) and without (n = 95) up-front neck dissection, propensity score matching was performed. RESULTS: Median follow-up was 48 months (range, 12-148). With up-front neck dissection, the hazard ratio for the primary end point, disease-free survival, was 0.63 (95% confidence interval: 0.37-1.06, P = .08). Up-front neck dissection reduced acute grade ≥3 toxicity significantly when xerostomia was excluded (odds ratio: 0.40, 95% confidence interval: 0.20-0.82, P = .012). CONCLUSION: Our results indicate less acute treatment toxicity without any significant difference in terms of oncologic outcome with up-front neck dissection prior to (chemo)radiotherapy as compared with (chemo)radiotherapy alone. Well-designed randomized trials are required to verify this result and further investigate the impact of this strategy on late toxicity and oncologic outcome.

Improved VMAT planning for head and neck tumors with an advanced optimization algorithm.

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 60-72 Gy in the PTV. The study is mainly focused on the phase 1 plans, which all have an identical PD of 54 Gy, 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 = 54 Gy) the near maximum dose D2% of the spinal cord, could be minimized to 22 ± 5 Gy with PRO3, as compared to 32 ± 12 Gy 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.

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

PURPOSE: To 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. METHODS: Data 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). RESULTS: Fifty 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. CONCLUSION: The 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.

Superior vena cava syndrome in thoracic malignancies.

The superior vena cava syndrome (SVCS) comprises various symptoms due to occlusion of the SVC, which can be easily obstructed by pathological conditions (eg, lung cancer, due to the low internal venous pressure within rigid structures of the thorax [trachea, right bronchus, aorta]). The resulting increased venous pressure in the upper body may cause edema of the head, neck, and upper extremities, often associated with cyanosis, plethora, and distended subcutaneous vessels. Despite the often striking clinical presentation, SVCS itself is usually not a life-threatening condition. Currently, randomized controlled trials on many clinically important aspects of SVCS are lacking. This review gives an interdisciplinary overview of the pathophysiology, etiology, clinical manifestations, diagnosis, and treatment of malignant SVCS.

Stereotactic radiation treatment planning and follow-up studies involving fused multimodality imaging.

OBJECT: Innovative new software solutions may enable image fusion to produce the desired data superposition for precise target definition and follow-up studies in radiosurgery/stereotactic radiotherapy in patients with intracranial lesions. The aim is to integrate the anatomical and functional information completely into the radiation treatment planning and to achieve an exact comparison for follow-up examinations. Special conditions and advantages of BrainLAB's fully automatic image fusion system are evaluated and described for this purpose. METHODS: In 458 patients, the radiation treatment planning and some follow-up studies were performed using an automatic image fusion technique involving the use of different imaging modalities. Each fusion was visually checked and corrected as necessary. The computerized tomography (CT) scans for radiation treatment planning (slice thickness 1.25 mm), as well as stereotactic angiography for arteriovenous malformations, were acquired using head fixation with stereotactic arc or, in the case of stereotactic radiotherapy, with a relocatable stereotactic mask. Different magnetic resonance (MR) imaging sequences (T1, T2, and fluid-attenuated inversion-recovery images) and positron emission tomography (PET) scans were obtained without head fixation. Fusion results and the effects on radiation treatment planning and follow-up studies were analyzed. The precision level of the results of the automatic fusion depended primarily on the image quality, especially the slice thickness and the field homogeneity when using MR images, as well as on patient movement during data acquisition. Fully automated image fusion of different MR, CT, and PET studies was performed for each patient. Only in a few cases was it necessary to correct the fusion manually after visual evaluation. These corrections were minor and did not materially affect treatment planning. High-quality fusion of thin slices of a region of interest with a complete head data set could be performed easily. The target volume for radiation treatment planning could be accurately delineated using multimodal information provided by CT, MR, angiography, and PET studies. The fusion of follow-up image data sets yielded results that could be successfully compared and quantitatively evaluated. CONCLUSIONS: Depending on the quality of the originally acquired image, automated image fusion can be a very valuable tool, allowing for fast (approximately 1-2 minute) and precise fusion of all relevant data sets. Fused multimodality imaging improves the target volume definition for radiation treatment planning. High-quality follow-up image data sets should be acquired for image fusion to provide exactly comparable slices and volumetric results that will contribute to quality contol.

Molecular whole-body cancer staging using positron emission tomography: consequences for therapeutic management and metabolic radiation treatment planning.

A prospective analysis was performed in 124 non-small cell lung cancer patients to determine the role of F-18 fluorodeoxyglucose (FDG)-positron emission tomography (PET) for molecular (metabolic) staging (n=63), therapy monitoring after induction-chemotherapy (n=34), and conformal radiation treatment planning (n=27). Staging by FDG-PET was significantly more accurate than CT (p<0.001) and changed therapeutic management in 52% of all patients. After induction-chemotherapy, patients with complete metabolic remission histologically did not show vital tumor cells in contrast to patients with metabolic partial remission or progressive disease. Metabolic radiation treatment planning by PET led to smaller planning target volumes (PTVs) for radiation therapy (between 3% and 21% in 25/27 patients), resulting in a reduction of dose exposure to healthy tissue. In two patients, PET-PTV was larger than CT-based PTV, since PET detected lymph node metastases smaller than 1 cm. FDG-PET provides clinically important information; changes therapeutic management, can predict noninvasively effectiveness of chemotherapy, and may lead to better tumor control with less radiation-induced toxicity.