The impact of local control on overall survival after stereotactic body radiotherapy for liver and lung metastases from colorectal cancer: a combined analysis of 388 patients with 500 metastases.

BACKGROUND: The aim of this analysis was to model the effect of local control (LC) on overall survival (OS) in patients treated with stereotactic body radiotherapy (SBRT) for liver or lung metastases from colorectal cancer. METHODS: The analysis is based on pooled data from two retrospective SBRT databases for pulmonary and hepatic metastases from 27 centers from Germany and Switzerland. Only patients with metastases from colorectal cancer were considered to avoid histology as a confounding factor. An illness-death model was employed to model the relationship between LC and OS. RESULTS: Three hundred eighty-eight patients with 500 metastatic lesions (lung n = 209, liver n = 291) were included and analyzed. Median follow-up time for local recurrence assessment was 12.1 months. Ninety-nine patients with 112 lesions experienced local failure. Seventy-one of these patients died after local failure. Median survival time was 27.9 months in all patients and 25.4 months versus 30.6 months in patients with and without local failure after SBRT. The baseline risk of death after local failure exceeds the baseline risk of death without local failure at 10 months indicating better survival with LC. CONCLUSION: In CRC patients with lung or liver metastases, our findings suggest improved long-term OS by achieving metastatic disease control using SBRT in patients with a projected OS estimate of > 12 months.

The SBRT database initiative of the German Society for Radiation Oncology (DEGRO): patterns of care and outcome analysis of stereotactic body radiotherapy (SBRT) for liver oligometastases in 474 patients with 623 metastases.

BACKGROUND: The intent of this pooled analysis as part of the German society for radiation oncology (DEGRO) stereotactic body radiotherapy (SBRT) initiative was to analyze the patterns of care of SBRT for liver oligometastases and to derive factors influencing treated metastases control and overall survival in a large patient cohort. METHODS: From 17 German and Swiss centers, data on all patients treated for liver oligometastases with SBRT since its introduction in 1997 has been collected and entered into a centralized database. In addition to patient and tumor characteristics, data on immobilization, image guidance and motion management as well as dose prescription and fractionation has been gathered. Besides dose response and survival statistics, time trends of the aforementioned variables have been investigated. RESULTS: In total, 474 patients with 623 liver oligometastases (median 1 lesion/patient; range 1­4) have been collected from 1997 until 2015. Predominant histologies were colorectal cancer (n = 213 pts.; 300 lesions) and breast cancer (n = 57; 81 lesions). All centers employed an SBRT specific setup. Initially, stereotactic coordinates and CT simulation were used for treatment set-up (55%), but eventually were replaced by CBCT guidance (28%) or more recently robotic tracking (17%). High variance in fraction (fx) number (median 1 fx; range 1­13) and dose per fraction (median: 18.5 Gy; range 3­37.5 Gy) was observed, although median BED remained consistently high after an initial learning curve. Median follow-up time was 15 months; median overall survival after SBRT was 24 months. One- and 2-year treated metastases control rate of treated lesions was 77% and 64%; if maximum isocenter biological equivalent dose (BED) was greater than 150 Gy EQD2Gy, it increased to 83% and 70%, respectively. Besides radiation dose colorectal and breast histology and motion management methods were associated with improved treated metastases control. CONCLUSION: After an initial learning curve with regards to total cumulative doses, consistently high biologically effective doses have been employed translating into high local tumor control at 1 and 2 years. The true impact of histology and motion management method on treated metastases control deserve deeper analysis. Overall survival is mainly influenced by histology and metastatic tumor burden.

The relevance of the lymph node ratio as predictor of prognosis is higher in HPV-negative than in HPV-positive oropharyngeal squamous cell carcinoma.

OBJECTIVES: Lymph node ratio (LNR) is an established predictor in different entities of carcinoma, including head and neck malignancies. In oropharyngeal squamous cell carcinoma (OPSCC), lymph node involvement differs between human papilloma virus (HPV)-positive and HPV-negative tumours. Herein, we evaluate the impact of HPV association on the concept of LNR. METHODS: 88 surgically treated patients were included in this retrospective chart review. HPV-positive and HPV-negative OPSCC were evaluated for prediction of outcome by LNR separately. The endpoints were 5-year overall survival (OS) and recurrence-free survival (RFS). RESULTS: The OS of all patients was 60.1%. In univariate analysis, LNR was a significant predictor of overall survival rate (P=.008) in OPSCC independently of the HPV status, as well as extracapsular spread (ECS). T-classification was only a significant predictor in the univariate analysis in HPV-positive OPSCC carcinoma. However, in the multivariate analysis LNR remained predictor of prognosis in all OPSCC and in HPV-negative OPSCC. In patients with HPV-positive OPSCC, only T-classification reached significance to predict OS. CONCLUSION: Prognosis of primarily operated HPV-positive patients might be more dependent on the extent of primary tumour site, whereas prognosis of HPV-negative patients is based more on cervical metastatic spread, represented by LNR.

[CyberKnife®: new treatment option for uveal melanoma]. / CyberKnife®: Eine neue Therapieoption bei uvealem Melanom.

BACKGROUND: CyberKnife® stereotactic radiosurgery is a new treatment option for uveal melanoma. OBJECTIVE: This review outlines the technique of robot-assisted CyberKnife® therapy, as well as the pros and cons in the treatment of uveal melanoma. METHODS: The study provides a PubMed literature review and own preliminary clinical experiences. RESULTS: CyberKnife® therapy for choroidal and ciliary body melanomas shows comparable results concerning local tumor control and overall survival matching those of conventional therapies. With only low complication rates, a high level of quality of life can be conserved by possible preservation of visual acuity as well as the ocular globe. CONCLUSION: Stereotactic radiosurgery using CyberKnife® seems to be an efficient and safe therapeutic option for malignant melanomas affecting the choroid and ciliary body. Comparative studies with conventional radiation strategies are now a high priority.

Neoadjuvant chemotherapy or chemoradiation for patients with advanced adenocarcinoma of the oesophagus? A propensity score-matched study.

BACKGROUND: Multimodal therapies are the standard of care for advanced adenocarcinomas of the oesophagus and gastro-oesophageal junction (AEG Types I and II). Only three randomised trials have compared preoperative chemotherapy with and without radiation. The results showed a small benefit for combined chemoradiation. In the meantime, newer therapy protocols are available. AIM: In a propensity-score matched study, we analysed patients with locally advanced AEG type I or II, treated with chemotherapy (FLOT-protocol) or chemoradiation (CROSS-protocol), followed by oesophagectomy, in a single high-volume centre. PATIENTS AND METHODS: Between 2011 and 2015, 137 patients with advanced (cT3NxcM0) adenocarcinoma received pre-operative therapy; 70% had chemoradiation (CROSS-protocol) and 30% had chemotherapy (FLOT-protocol). After propensity-score matching, 40 patients from the CROSS-group were selected for analysis. Postoperative histopathological response and prognosis were analysed. RESULTS: The two groups were comparable according to the matching criteria age, gender, tumour location, and year of surgery. R0-resection was achieved in 97% of patients in the CROSS-group and 85% of the FLOT-group (p = 0.049). Major response of the primary tumour was evident more often in the CROSS-group (17/40 pts. 43%) versus FLOT-group (11/40 pts. 27%) as well no lymph node metastasis (ypN0 = 68% versus ypN0 = 40%) (p = 0.014). Prognosis were not significantly different between the two groups. In multivariate analysis, only ypN-category was an independent prognostic factor. CONCLUSION: Compared to FLOT-chemotherapy, neoadjuvant chemoradiotherapy with the CROSS-protocol in locally advanced adenocarcinoma AEG types I and II resulted in better response by the primary tumour and less lymph node metastasis but without superior survival.

Interobserver variability in target volume delineation of hepatocellular carcinoma : An analysis of the working group "Stereotactic Radiotherapy" of the German Society for Radiation Oncology (DEGRO).

BACKGROUND: Definition of gross tumor volume (GTV) in hepatocellular carcinoma (HCC) requires dedicated imaging in multiple contrast medium phases. The aim of this study was to evaluate the interobserver agreement (IOA) in gross tumor delineation of HCC in a multicenter panel. METHODS: The analysis was performed within the "Stereotactic Radiotherapy" working group of the German Society for Radiation Oncology (DEGRO). The GTVs of three anonymized HCC cases were delineated by 16 physicians from nine centers using multiphasic CT scans. In the first case the tumor was well defined. The second patient had multifocal HCC (one conglomerate and one peripheral tumor) and was previously treated with transarterial chemoembolization (TACE). The peripheral lesion was adjacent to the previous TACE site. The last patient had an extensive HCC with a portal vein thrombosis (PVT) and an inhomogeneous liver parenchyma due to cirrhosis. The IOA was evaluated according to Landis and Koch. RESULTS: The IOA for the first case was excellent (kappa: 0.85); for the second case moderate (kappa: 0.48) for the peripheral tumor and substantial (kappa: 0.73) for the conglomerate. In the case of the peripheral tumor the inconsistency is most likely explained by the necrotic tumor cavity after TACE caudal to the viable tumor. In the last case the IOA was fair, with a kappa of 0.34, with significant heterogeneity concerning the borders of the tumor and the PVT. CONCLUSION: The IOA was very good among the cases were the tumor was well defined. In complex cases, where the tumor did not show the typical characteristics, or in cases with Lipiodol (Guerbet, Paris, France) deposits, IOA agreement was compromised.

Stereotactic body radiotherapy for oligo-metastatic liver disease - Influence of pre-treatment chemotherapy and histology on local tumor control.

INTRODUCTION: Stereotactic body radiation therapy (SBRT) is applied in the oligometastatic setting to treat liver metastases. However, factors influencing tumor control probability (TCP) other than radiation dose have not been thoroughly investigated. Here we set out to investigate such factors with a focus on the influence of histology and chemotherapy prior to SBRT using a large multi-center database from the German Society of Radiation Oncology. METHODS: 452 SBRT treatments in 363 patients were analyzed after collection of patient, tumor and treatment data in a multi-center database. Histology was considered through random effects in semi-parametric and parametric frailty models. Dose prescriptions were parametrized by conversion to the maximum biologically effective dose using alpha/beta of 10Gy (BEDmax). RESULTS: After adjusting for histology, BEDmax was the strongest predictor of TCP. Larger PTV volumes, chemotherapy prior to SBRT and simple motion management techniques predicted significantly lower TCP. The model predicted a BED of 209±67Gy10 necessary for 90% TCP at 2years with no prior chemotherapy, but 286±78Gy10 when chemotherapy had been given. Breast cancer metastases were significantly more responsive to SBRT compared to other histologies with 90% TCP at 2years achievable with BEDmax of 157±80Gy10 or 80±62Gy10 with and without prior chemotherapy, respectively. CONCLUSIONS: Besides dose, histology and pretreatment chemotherapy were important factors influencing local TCP in this large cohort of liver metastases. After adjusting for prior chemotherapy, our data add to the emerging evidence that breast cancer metastases do respond better to hypofractionated SBRT compared to other histologies.

Prediction of outcome by lymph node ratio in patients with parotid gland cancer.

OBJECTIVE: Lymph node ratio (LNR) has been shown to be an independent predictor of recurrence risk and survival in different entities of carcinoma. METHODS: In this retrospective chart review, 128 patients with parotid gland cancer (PGC) subsequently treated by primary surgery were included. About 64% (n = 82) of these patients were additionally treated with adjuvant radiotherapy. Five-year overall survival rates were determined by subgroups based on LNR value. RESULTS: Lymph node ratio was found to be significantly associated with overall survival rate (P < 0.001). Using univariate analyses, pathological tumour-node-metastasis (TNM)-stage, UICC-stage grouping and extracapsular spread were found to be significant predictors of overall survival (P < 0.001). However, with a multivariate analyses, LNR remained the only independent predictor of overall survival (P = 0.043). CONCLUSIONS: After surgery for PGC, evaluation of the neck using LNR was found to reliably stratify the overall survival rate.

Checkpoint inhibitors and radiation treatment in Hodgkin's lymphoma : New study concepts of the German Hodgkin Study Group.

BACKGROUND: Patients with classical Hodgkin's lymphoma (cHL) have a good prognosis even in advanced stages. However, combined chemo- and radiotherapy, as the standard of care, is also associated with treatment-related toxicities such as organ damage, secondary neoplasias, infertility, or fatigue and long-term fatigue. Many patients suffer from this burden although their cHL was cured. Therefore, the efficacy of immune checkpoint inhibitors like anti-PD1/PD-L1 antibodies in the treatment of solid cancers and also in HL offers new options. A remarkable and durable response rate with a favorable toxicity profile was observed in heavily pretreated cHL patients. METHODS: Planning to perform prospective randomized clinical trials in the content of radio-immune treatment in patients with Hodgkin's lymphoma (HL), we transferred the results of preliminary clinical studies and basic research in clinical relevant study concepts. RESULTS: Based on these promising early phase trial data, the German Hodgkin Study Group (GHSG) will investigate innovative treatment regimens in upcoming phase II trials. CONCLUSION: The therapeutic efficacy and potential synergies of anti-PD1 antibodies in combination with chemo- or radiotherapy will be investigated in various settings of HL.

[Second neoplasms after percutaneous radiotherapy]. / Sekundärmalignome nach perkutaner Radiotherapie.

Radiation therapy represents an alternative treatment to radical prostatectomy in the management of clinically localized prostate cancer. Radiation-induced second neoplasms are defined by a latency period of at least 5 years, location within the field of radiation therapy, and a histology which differs from the primary tumor. Based on the data in the literature, there is a consistently increased risk of bladder cancer (HR: 1.67, 95% CI 1.55-1.80), rectal cancer (HR: 1.79, 95% CI 1.34-2.38), and colorectal cancer (HR: 1.79, 95% CI 1.34-23.8) following percutaneous radiation therapy. Following brachytherapy only an increased for the development of bladder cancer (HR: 2.14, 95% CI 1.03-3.94) has been observed. The incidence of second neoplasms increases significantly and continuously with the posttreatment time interval. Although bladder cancers following RT of the prostate are usually more locally advanced and of high grade, no negative impact in terms of overall survival and cancer-specific survival has been observed. Symptoms or findings of microhematuria need to be examined thoroughly after radiation therapy to identify bladder cancer quite early.

Endocrine and visual function after fractionated stereotactic radiotherapy of perioptic tumors.

PURPOSE: To find out whether the use of stereotactic techniques for fractionated radiotherapy reduces toxicity to the endocrine and visual system in patients with benign perioptic tumors. PATIENTS AND METHODS: From 1993 to 2009, 29 patients were treated with fractionated stereotactic radiotherapy. The most frequent tumor types were grade I meningioma (n = 11) and pituitary adenoma (n = 10, 7 nonfunctioning, 3 growth hormone-producing). Patients were immobilized with the GTC frame (Radionics, USA) and the planning target volume (PTV; median 24.7, 4.6-58.6 ml) was irradiated with a total dose of 52.2 Gy (range, 45.0-55.8 Gy) in 1.8-Gy fractions using a linear accelerator (6 MeV photons) equipped with a micro-multileaf collimator. Maximum doses to the optic system and pituitary gland were 53.4 Gy (range, 11.5-57.6 Gy) and 53.6 Gy (range, 12.0-57.9 Gy). RESULTS: Median follow-up was 45 months (range, 10-105 months). Local control was achieved in all but 1 patient (actuarial rate 92% at 5 years and 10 years). In 9 of 29 patients (31%), partial remission was observed (actuarial response rate 40% at 5 years and 10 years). In 4 of 26 patients (15%) with at least partial pituitary function, new hormonal deficits developed (actuarial rate 21% at 5 years and 10 years). This rate was significantly higher in patients treated for a larger PTV (< /> 25 ml: 0% vs. 42% at 5 years and 10 years, p = 0.028). Visual function improved in 4 of 15 patients (27%) who had prior impairment. None of the patients developed treatment-related optic neuropathy, but 2 patients experienced new disease-related visual deficits. CONCLUSION: Fractionated stereotactic radiotherapy for benign tumors of the perioptic and sellar region results in satisfactory response and local control rates and does not affect the visual system. The assumption that patients can be spared hypophyseal insufficiency only holds for small tumors.

Radiotherapy in elderly patients with inoperable esophageal cancer. Is there a benefit?

BACKGROUND: Radiation oncologists increasingly face elderly cancer patients impaired by comorbidities and reduced performance status. As less data are available for this particular group of patients, the aim of the study was to assess the prognosis of inoperable esophageal cancer patients ≥ 70 years undergoing definitive radiotherapy or radiochemotherapy. PATIENTS AND TREATMENT PROTOCOL: Patients aged ≥ 70 with inoperable carcinoma of the esophagus undergoing definitive radio(chemo)therapy between 1995 and 2006 at the University of Cologne were included retrospectively. Maximal total dose of radiotherapy administered was 63 Gy (5 × 1.8 Gy/week). Chemotherapy consisted of cisplatin (20 mg/m(2) on days 1-5 and days 29-33) and 5-fluorouracil (650-1,000 mg/m(2) on days 1-5 and days 29-33). Efficacy was compared with a cohort of 152 patients < 70 years treated with the same protocol during the same time period. RESULTS: A total of 51 patients aged ≥ 70 with inoperable cancer of the esophagus undergoing definitive therapy were identified (stage I/II 23.5%, stage III 56.9%, stage IV 9.8%; squamous cell carcinoma 74.5%, adenocarcinoma 25.5%). While 15 patients (29.4%) received combined radiochemotherapy (RCT), 40 patients (70.6%) were treated with radiotherapy alone (RT). Median progression-free survival (PFS) was 9.5 months; median overall survival (OS) was 13.9 months. Patients treated with RCT had a 2-year OS rate of 53.3% compared with 16.7% for RT patients (p = 0.039). The 2-year OS for clinically lymph node negative patients was 38.5% compared with 21.2% for lymph node positive patients (p = 0.072). Median OS was not significantly different between patients ≥ 70 years versus the patient cohort (n = 152) aged < 70 years (13.9 vs. 7.2 months, p = 0.072) but PFS showed a significant difference (4.9 vs. 9.5 months, p = 0.026) in favor of the > 70 years group. CONCLUSION: Prognosis in elderly patients with inoperable esophageal cancer undergoing definitive radiotherapy/radiochemotherapy is limited, although it is not inferior to patients < 70 years.

Prognostic factors in definitive radiochemotherapy of advanced inoperable esophageal cancer.

The aim of this study was to assess the efficacy and prognostic factors of definitive radiochemotherapy (RCT) for inoperable esophageal cancer. Between 1995 and 2005 all patients with inoperable esophageal cancer that underwent concurrent RCT were included in this retrospective study. Conventional computed tomography-based treatment planning as well as 3D-conformal radiotherapy (RT) was used. Maximum radiotherapy dose was 63 Gy. Chemotherapy consisted of cisplatin (20 mg/m(2) d1-5 and 29-33) and 5-FU (650-1000 mg/m(2) d1-5 and 29-33). Patients not suitable for RCT received radiotherapy alone. Toxicity was measured according to common toxicity criteria (CTC). Two hundred three consecutive patients with inoperable esophageal cancer that received definitive therapy were identified in this time period (160 with squamous cell carcinoma and 43 with adenocarcinoma). The 2-year overall survival probability was 21.2% whereas the progression-free survival at 2 years was 13.8% for all patients. In the univariate analysis, type of histology, T-stage, N-stage, application of chemotherapy, and the radiation dose were significantly correlated with overall/progression-free survival. Moreover, multivariate analysis revealed an independent prognostic impact for N-stage, radiation dose, and concurrent chemotherapy. Definitive RCT is an important palliative treatment option for patients with inoperable esophageal cancer. N-stage, radiation dose, and concurrent chemotherapy are important prognostic factors for survival.

[Update on HPV-induced oropharyngeal cancer]. / Aktuelles zu HPV-induzierten Oropharynxkarzinomen.

Oropharyngeal squamous cell carcinoma (OSCC) is associated with oncogenic human papillomavirus (HPV) infection in 30-40% of all cases in Germany. The use of PCR and / or in situ hybridisation to detect HPV in tumour tissue is used in combination with p16 immunohistochemistry to reliably distinguish HPV-related and HPV-unrelated OSCC. The distinct biological behaviour of the HPV-related subset of OSCC results in a more favourable prognosis. This might be the result of a greater response to chemotherapy and radiotherapy as seen in recent studies. Ongoing and future clinical trials will stratify for HPV status. If the results of these prospective, randomized trials are consistent with the preliminary results of recent studies, HPV status will be of enormous clinical relevance in the future.

[Neoadjuvant therapy of adenocarcinomas of the upper gastrointestinal tract. Status of radiotherapy]. / Neoadjuvante Therapie der Adenokarzinome des oberen Gastrointestinaltraktes. Rolle der Strahlentherapie.

Radiotherapy in combination with simultaneous chemotherapy can improve survival of advanced esophageal adenocarcinoma. The extent of histopathological tumor regression achieved by the therapy is a relevant prognostic factor for this tumor entity. Response evaluation after radiochemotherapy of esophageal carcinoma will rely more and more on molecular factors and will allow individualization of the therapy. New combinations with taxanes and irinotecan as well as EGF receptor antagonists need to be evaluated in phase III trials. Postoperative chemoradiation and perioperative chemotherapy are evaluated in gastric adenocarcinomas and show a survival advantage. Surgery techniques used in theses trials are not recommended in current clinical guidelines.

[Radical salvage prostatectomy : Treatment of local recurrence of prostate cancer after radiotherapy]. / Die radikale Salvageprostatektomie : Therapie der lokalen Prostatakarzinomrezidivs nach Strahlentherapie.

External beam radiation and low- and high-dose interstitial brachytherapy represent therapeutic alternatives to radical prostatectomy for organ-confined and locally advanced prostate cancer. Local recurrences are described in 5-35% of the patients depending on the individual risk profile, and most recurrences are detected due to asymptomatic PSA rise only. According to the most recent data, recurrences are defined by a PSA increase >2 ng/ml above the post-radiation nadir. Radical salvage prostatectomy represents a secondary local treatment with curative intent in patients with organ-confined recurrences. Preoperative risk factors predicting organ-confined disease are initial LDR brachytherapy, preoperative Gleason biopsy score < or =6, < or =50% biopsy cores involved with cancer, and a PSA doubling time >12 months. Metastatic disease should be ruled out preoperatively by skeletal scintigraphy, computed tomography, or magnetic resonance imaging of the abdomen and the small pelvis, and/or choline PET/CT. Functionality of the lower urinary tract is evaluated by urethrocystoscopy and urodynamics. The most appropriate candidates for radical salvage prostatectomy are patients with organ-confined disease or those with symptomatic local recurrences. In experienced hands, morbidity is low with a continence rate of 83-96% depending on the type of previous radiation therapy. Long-term oncological control can be achieved in more than 80% of the patients.

Nuclear survivin expression is associated with HPV-independent carcinogenesis and is an indicator of poor prognosis in oropharyngeal cancer.

The relationship between expression of the inhibitor of apoptosis protein survivin and the presence of high-risk human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma (OSCC) remains unclear. This also accounts for its role as a predictor of survival. Therefore, we conducted a multicentre retrospective study on 106 consecutive oropharyngeal cancer patients. Human papillomavirus sequences were detected by nested PCR protocols. Survivin and p16 expression as a surrogate marker for HPV status were analysed by immunohistochemistry. Sequences of high-risk HPV were detected in 29% of cases. Prominent cytoplasmatic expression of survivin was found in 58% of cases and nuclear expression of survivin was found in 19% of the survivin-positive tumours. Nuclear expression of survivin was significantly correlated with HPV-negative tumours (P=0.023) and with a poor disease-free survival rate with an estimated 3-year disease-free survival probability of 35% for tumours with nuclear expression of survivin vs 78% for tumours with non-nuclear expression of survivin (hazard ratio=8.264; 95% confidence interval (95% CI)=2.510-27.210; P<0.001). In multivariate analysis, p16 expression status as well as nuclear expression of survivin were strong independent and opposing prognostic indicators of disease-free survival (hazard ratio=0.068; 95% CI=0.005-0.892; P=0.041 and hazard ratio=15.975; 95% CI=2.377-107.360; P=0.004, respectively). Our data show that nuclear accumulation of survivin correlates with HPV-independent carcinogenesis and is an independent predictor of poor survival in patients with OSCC.

Long-term results of the combined modality therapy for advanced cervical metastatic head and neck squamous cell carcinoma.

AIM: A consensus treatment strategy for advanced cervical metastatic head and neck squamous cell carcinoma has not been established. The aim of this retrospective study was to investigate the outcome of these patients uniformely using a strategy which consists of surgery for the primary tumor and the neck metastases followed by postoperative radio(chemo)therapy. METHODS: We included a selected series of 518 patients with previously untreated head and neck squamous cell carcinoma. The overall survival (OS), the disease specific survival (DSS), the disease free survival (DFS), the local control (LC) and regional control (RC) estimates were calculated. The statistical relationship of various clinical and histopathological variables on the above mentioned estimates were analyzed. RESULTS: The overall survival probability was 73.2% for pN0 stage, 43% for pN>1 stages and 31% for pN2c/pN3 stages. The pN stage significantly influenced the survival probabilities in oropharyngeal (p=0.0001) and laryngeal tumors (p<0.0001) in univariate analyses. In multivariate analysis, age, pT stage, pN stage, M stage, and extranodal spreading were independent risk factors for decreased disease-specific survival. CONCLUSIONS: We could show that pN stage is an important independent prognostic factor in head and neck cancer. The presented multimodal treatment protocol provides excellent oncological outcomes and should therefore be standard of care for patients with operable advanced cervical metastatic head and neck squamous cell carcinoma.

Single modality and multimodality treatment of nasal and paranasal sinuses cancer: a single institution experience of 229 patients.

AIMS: To assess the single and multimodal treatment results and prognostic factors for sinonasal carcinoma. METHODS: Overall survival (OS), disease-specific survival (DSS), local control (LC), and disease-free survival (DFS) in 229 patients with sinonasal carcinoma treated from 1967 to 2003 were calculated. Prognostic factors were univariately and multivariately analyzed. The median follow-up period for survivors was 126 months. RESULTS: 32% of the patients were operated only, 47% underwent multimodal therapy, and 20% were treated without operation. The 5-year OS rate was 41%, and the DSS rate was 51%. The LC rate was 64%, and the DFS rate was 34%. Prognostic for DSS were M status (p<0.001), UICC stage (p<0.001), T classification (p=0.001), N status (p=0.002), intracranial tumor infiltration (p=0.008), infiltration of the pterygopalatine fossa (p=0.02), infiltration of the skull base (p=0.021), infiltration of the orbita (p=0.041), and the type of therapy (p<0.001): The 5-year DSS rate was 63% for patients operated only, 56% for all operated patients, 46% for patients undergoing surgery and radiotherapy, but only 21% for patients treated with radiotherapy+/-chemotherapy. Multivariate analysis revealed that T classification (p=0.042), N classification (p=0.035), M classification (p=0.007), UICC stage (p=0.038), and type of therapy (p=0.038) were independent prognostic factors for DSS. CONCLUSIONS: Radical surgery is recommended for stage I/II sinonasal carcinomas. Stage III/IV carcinomas still have a poor prognosis, but multimodal treatment seems to favor the outcome.