Objectives: Patients with head and neck cancer (HNC) are often highly affected by disease and treatment, resulting in impaired physical functioning and quality of life. Therefore, evaluation of... Show moreObjectives: Patients with head and neck cancer (HNC) are often highly affected by disease and treatment, resulting in impaired physical functioning and quality of life. Therefore, evaluation of patients' psychosocial and functional outcomes can be facilitated by patient-reported outcome measures (PROMs). By providing the patients' own perspectives, PROMs are crucial to improving patient-centered care. This study aimed to improve understanding of the perceived value of PROMs in HNC care and how to optimize their clinical value based on patients' and multidisciplinary healthcare professionals' (HCPs)Methods: Population-based surveys among patients with HNC through their patient association and among HCPs nationwide through the Dutch Head and Neck Audit.Results: A total of 54 patients and 40 multidisciplinary HCPs from all 14 nationwide HNC centers (100%) responded. For patients, the most important element of patient-reported outcome collection systems was including a call to action for those with worse-than-average scores (28%), whereas clinicians found discussing scores during clinical visits the most important (39%). Although 16% of clinicians found short completion time the most important element, none of the patients selected completion time as most important. Additionally, 17% of patients stated completion time was not an issue, provided clinicians would use the outcomes for clinical purposes.Conclusions: Although patients and clinicians acknowledged the value of patient-reported outcomes, patients would like to be more involved in the clinical implications of their outcomes. Enhancing patients' involvement by a call to action and providing feedback on their scores during outpatient clinic visits may improve the clinical value of PROMs. Show less
Verhoeff, S.R.; Donk, P.P. van de; Aarntzen, E.H.J.G.; Oosting, S.F.; Brouwers, A.H.; Miedema, I.H.C.; ... ; Herpen, C.M.L. van 2022
In this PD-L1 ImagiNg to prediCt durvalumab treatment response in SCCHN (PINCH) study, we performed 89Zr-DFO-durvalumab (anti- PD-L1 [programmed death ligand 1]) PET/CT in patients with recurrent... Show moreIn this PD-L1 ImagiNg to prediCt durvalumab treatment response in SCCHN (PINCH) study, we performed 89Zr-DFO-durvalumab (anti- PD-L1 [programmed death ligand 1]) PET/CT in patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) before monotherapy durvalumab treatment. The primary aims were to assess safety and feasibility of 89Zr-DFO-durvalumab PET imag-ing and predict disease control rate during durvalumab treatment. Sec-ondary aims were to correlate 89Zr-DFO-durvalumab uptake to tumor PD-L1 expression, 18F-FDG uptake, and treatment response of individ-ual lesions.Methods: In this prospective multicenter phase I-II study (NCT03829007), patients with incurable R/M SCCHN underwent base-line 18F-FDG PET and CT or MRI. Subsequently, PD-L1 PET imaging was performed 5 d after administration of 37 MBq of 89Zr-DFO-durvalumab. To optimize imaging conditions, dose finding was per-formed in the first 14 patients. For all patients (n = 33), durvalumab treatment (1,500 mg/4 wk, intravenously) was started within 1 wk after PD-L1 PET imaging and continued until disease progression or unacceptable toxicity (maximum, 24 mo). CT evaluation was assessed according to RECIST 1.1 every 8 wk. PD-L1 expression was deter-mined by combined positive score on (archival) tumor tissue. 89Zr-DFO-durvalumab uptake was measured in 18F-FDG-positive lesions, primary and secondary lymphoid organs, and blood pool.Results: In total, 33 patients with locoregional recurrent (n = 12) or metastatic SCCHN (n = 21) were enrolled. 89Zr-DFO-durvalumab injection was safe. A dose of 10 mg of durvalumab resulted in highest tumor-to-blood ratios. After a median follow-up of 12.6 mo, overall response rate was 26%. The disease control rate at 16 wk was 48%, with a mean duration of 7.8 mo (range, 1.7-21.1). On a patient level, 89Zr-DFO-durvalumab SUVpeak or tumor-to-blood ratio could not predict treatment response (hazard ratio, 1.5 [95% CI, 0.5-3.9; P = 0.45] and 1.3 [95% CI, 0.5-3.3; P = 0.60], respectively). Also, on a lesion level, 89Zr-DFO-durvalumab SUVpeak showed no substantial correlation to treatment response (Spearman p, 0.45; P = 0.051). Lesional 89Zr-DFO-durvalumab uptake did not correlate to PD-L1 combined positive score but did correlate to 18F-FDG SUVpeak (Spearman p, 0.391; P = 0.005).Conclusion: PINCH is the first, to our knowledge, PD-L1 PET/CT study in patients with R/M SCCHN and has shown the feasibility and safety of 89Zr-DFO-durvalumab PET/CT in a multicenter trial. 89Zr-DFO-durvalumab uptake did not correlate to durvalumab treat-ment response. Show less
Gruijs, M.; Ganzevles, S.H.; Stigter-van Walsum, M.; Mast, R. van der; Ostaijen-ten Dam, M.M. van; Tuk, C.W.; ... ; Bakema, J.E. 2021
The immunosuppressive character of head and neck cancers may explain the relatively low response rates to antibody therapy targeting a tumor antigen, such as cetuximab, and anti-PD-1 checkpoint... Show moreThe immunosuppressive character of head and neck cancers may explain the relatively low response rates to antibody therapy targeting a tumor antigen, such as cetuximab, and anti-PD-1 checkpoint inhibition. Immunostimulatory agents that overcome tumor-derived inhibitory signals could augment therapeutic efficacy, thereby enhancing tumor elimination and improving patient survival. Here, we demonstrate that cetuximab treatment combined with immunostimulatory agonists for Toll-like receptor (TLR) 2 induces profound immune responses. Natural killer (NK) cells, isolated from healthy individuals or patients with head and neck cancer, harbored enhanced cytotoxic capacity and increased tumor-killing potential in vitro. Additionally, combination treatment increased the release of several pro-inflammatory cytokines and chemokines by NK cells. Tumor-bearing mice that received cetuximab and the TLR2 ligand Pam3CSK4 showed increased infiltration of immune cells into the tumors compared to mice that received cetuximab monotherapy, resulting in a significant delay in tumor growth or even complete tumor regression. Moreover, combination treatment resulted in improved overall survival in vivo. In conclusion, combining tumor-targeting antibody-based immunotherapy with TLR stimulation represents a promising treatment strategy to improve the clinical outcomes of cancer patients. This treatment could well be applied together with other therapeutic strategies such as anti-PD-(L)1 checkpoint inhibition to further overcome immunosuppression. Show less
Buckle, T.; Alphen, M. van; Oosterom, M.N. van; Beurden, F. van; Heimburger, N.; Wal, J.E. van der; ... ; Karakullukcu, B. 2021
Simple SummaryTranslation of tumor-specific fluorescent tracers is crucial in the realization intraoperative of tumor identification during fluorescence-guided surgery. Ex vivo assessment of... Show moreSimple SummaryTranslation of tumor-specific fluorescent tracers is crucial in the realization intraoperative of tumor identification during fluorescence-guided surgery. Ex vivo assessment of surgical specimens after topical tracer application has the potential to reveal the suitability of a potential surgical target prior to in vivo use in patients. In this study, the c-Met receptor was identified as a possible candidate for fluorescence-guided surgery in oral cavity cancer. Freshly excised tumor specimens obtained from ten patients with squamous cell carcinoma of the tongue were incubated with EMI-137 and imaged with a clinical-grade Cy5 prototype fluorescence camera. In total, 9/10 tumors were fluorescently illuminated, while non-visualization could be linked to non-superficial tumor localization. Immunohistochemistry revealed c-Met expression in all ten specimens. Tumor assessment was improved via video representation of the tumor-to-background ratio.Intraoperative tumor identification (extension/margins/metastases) via receptor-specific targeting is one of the ultimate promises of fluorescence-guided surgery. The translation of fluorescent tracers that enable tumor visualization forms a critical component in the realization of this approach. Ex vivo assessment of surgical specimens after topical tracer application could help provide an intermediate step between preclinical evaluation and first-in-human trials. Here, the suitability of the c-Met receptor as a potential surgical target in oral cavity cancer was explored via topical ex vivo application of the fluorescent tracer EMI-137. Freshly excised tumor specimens obtained from ten patients with squamous cell carcinoma of the tongue were incubated with EMI-137 and imaged with a clinical-grade Cy5 prototype fluorescence camera. In-house developed image processing software allowed video-rate assessment of the tumor-to-background ratio (TBR). Fluorescence imaging results were related to standard pathological evaluation and c-MET immunohistochemistry. After incubation with EMI-137, 9/10 tumors were fluorescently illuminated. Immunohistochemistry revealed c-Met expression in all ten specimens. Non-visualization could be linked to a more deeply situated lesion. Tumor assessment was improved via video representation of the TBR (median TBR: 2.5 (range 1.8-3.1)). Ex vivo evaluation of tumor specimens suggests that c-Met is a possible candidate for fluorescence-guided surgery in oral cavity cancer. Show less
Valstar, M.H.; Schaapveld, M.; Broek, E.C. van den; Velthuysen, M.L.F. van; Ridder, M. de; Schmidt, M.K.; ... ; Smeele, L.E. 2020
Salivary and mammary gland tumors show morphological similarities and share various characteristics, including frequent overexpression of hormone receptors and female preponderance. Although this... Show moreSalivary and mammary gland tumors show morphological similarities and share various characteristics, including frequent overexpression of hormone receptors and female preponderance. Although this may suggest a common etiology, it remains unclear whether patients with a salivary gland tumor carry an increased risk of breast cancer (BC). Our purpose was to determine the risk of BC in women diagnosed with salivary gland carcinoma (SGC) or pleomorphic adenoma (SGPA). BC incidence (invasive and in situ) was assessed in two nationwide cohorts: one comprising 1567 women diagnosed with SGC and one with 2083 women with SGPA. BC incidence was compared with general population rates using standardized incidence ratio (SIR). BC risk was assessed according to age at SGC/SGPA diagnosis, follow-up time and (for SGC patients) histological subtype. The mean follow-up was 7.0 years after SGC and 9.9 after SGPA diagnosis. During follow-up, 52 patients with SGC and 74 patients with SGPA developed BC. The median time to BC was 6 years after SGC and 7 after SGPA. The cumulative risk at 10 years of follow-up was 3.1% after SGC and 3.5% after SGPA (95% Confidence Interval (95%CI) 2.1%-4.7% and 2.6%-4.6%, respectively). BC incidence was 1.59 times (95%CI 1.19-2.09) higher in the SGC-cohort than expected based on incidence rates in the general population. SGPA-patients showed a 1.48 times (95%CI 1.16-1.86) higher incidence. Women with SGC or SGPA have a slightly increased risk of BC. The magnitude of risk justifies raising awareness, but is no reason for BC screening. Show less
Deudekom, F.J. van; Velden, L.A. van der; Zijl, W.H.; Schimberg, A.S.; Langeveld, A.P.; Slingerland, M.; ... ; Mooijaart, S.P. 2019
Background The aim is to describe the association of functional capacity and cognitive functioning with 1-year mortality in older patients with cancer in the head and neck region. Methods We... Show moreBackground The aim is to describe the association of functional capacity and cognitive functioning with 1-year mortality in older patients with cancer in the head and neck region. Methods We performed a cohort study in which all patients aged 70 years and older received a geriatric screening before treatment. Main outcome was 1-year mortality. Results A total of 102 patients were included. Median age was 78.7 years (interquartile range [IQR], 72.3-84.5), 25% were cognitive impaired, 40% were malnourished, and 28.4% used a walking device. Overall, 1-year mortality was 42.3%. Male sex (hazard ratio [HR], 4.30; 95% confidence interval [CI], 1.35-13.67), malnutrition (HR, 2.55; 95% CI, 1.19-5.16), and using a walking device (HR, 2.80; 95% CI 1.13-6.93) were associated with higher mortality risk, independent of stage and comorbidities. Conclusion In older patients with head and neck cancer, the mortality rates are high. Nutritional status and mobility are determinants of 1-year mortality, independent of tumor stage, age, and comorbidity. Show less
Heukelom, J.; Navran, A.; Gouw, Z.A.R.; Tesselaar, M.E.; Zuur, C.L.; Werkhoven, E. van; ... ; Al-Mamgani, A. 2019
Objective The aim of the current study was to determine the incidence of organ function preservation failure (OFPF) in patients with head and neck squamous cell carcinoma (HNSCC) treated by (chemo... Show moreObjective The aim of the current study was to determine the incidence of organ function preservation failure (OFPF) in patients with head and neck squamous cell carcinoma (HNSCC) treated by (chemo)radiotherapy and to identify its risk factors. Study Design Retrospective cohort analysis. Setting Tertiary cancer care center. Subjects and Methods A single-center retrospective cohort analysis was done (n = 703) in which OFPF after (chemo)radiotherapy was assessed. OFPF was defined as local failure or pure functional failure in the absence of local failure because of major surgical intervention (total laryngectomy, commando resection, permanent tracheostomy) or feeding tube dependence >2 years. Results OFPF occurred in 153 patients (21.8%). Reasons for OFPF were local failure in 103 patients (14.6%) and functional failure in 50 patients (7.2%). Evidence of functional failure included need for total laryngectomy (n = 9, 1.3%), commando resection (n = 2, 0.3%), permanent tracheostomy (n = 16, 2.3%), and/or long-term feeding tube for functional reasons (n = 23, 3.3%). In a Cox proportional hazards model, OFPF was worse for patients with T4 tumors (hazard ratio [HR] <0.5 and P < .001 for all other stages), for laryngeal vs oropharyngeal cancer (HR, 1.83; 95% confidence interval [CI], 1.20-2.79, P = .005, hypopharyngeal not significant), and for smokers (HR, 1.68; 95% CI, 1.10-2.56, P = .015). Exploratory multivariate analysis by tumor site showed that T4 tumor and pretreatment tracheostomy were the strongest predictive factors for OFPF in laryngeal and hypopharyngeal carcinoma while T4 tumor and smoking were predictive for poor OFPF in oropharyngeal carcinoma. Conclusion This work shows a detrimental effect of smoking on functional outcomes after (chemo-)radiotherapy for HNSCC. Moreover, T4 tumor, laryngeal subsite, and pretreatment tracheostomy are strong predictors of OFPF. Show less
Setup and range uncertainties compromise radiotherapy plan robustness. We introduce a method to evaluate the clinical effect of these uncertainties on the population using tumor control probability... Show moreSetup and range uncertainties compromise radiotherapy plan robustness. We introduce a method to evaluate the clinical effect of these uncertainties on the population using tumor control probability (TCP) and normal tissue complication probability (NTCP) models.Eighteen oropharyngeal cancer patients treated with curative intent were retrospectively included. Both photon (VMAT) and proton (IMPT) plans were created using a planning target volume as planning objective. Plans were recalculated for uncertainty scenarios: two for range over/undershoot (IMPT) or CT-density scaling (VMAT), six for shifts. An average shift scenario (< XYZ >) was calculated to assess random errors. Dose differences between nominal and scenarios were translated to TCP (2 models) and NTCP (15 models). A weighted average (W_Avg) of the TCP\NTCP based on Gaussian distribution over the variance scenarios was calculated to assess the clinical effect of systematic errors on the population.TCP/NTCP uncertainties were larger in IMPT compared to VMAT. Although individual perturbations showed risks of plan deterioration, the < XYZ > scenario did not show a substantial decrease in any of the TCP endpoints suggesting evaluated plans in this cohort were robust for random errors. Evaluation of the W_Avg scenario to assess systematic errors showed in VMAT no substantial decrease in TCP endpoints and in IMPT a limited decrease. In IMPT, the W_Avg scenario had a mean TCP loss of 0%-2% depending on plan type and primary or nodal control. The W_Avg for NTCP endpoints was around 0%, except for mandible necrosis in IMPT (W_Avg: 3%).The estimated population impact of setup and range uncertainties on TCP/NTCP following VMAT or IMPT of oropharyngeal cancer patients was small for both treatment modalities. The use of TCP/NTCP models allows for clinical interpretation of the population effect and could be considered for incorporation in robust evaluation methods.Highlights:TCP/NTCP models allow for a clinical evaluation of uncertainty scenarios.For this cohort, in silico-PTV based IMPT plans and VMAT plans were robust for random setup errors.Effect of systematic errors on the population was limited: mean TCP loss was 0%-2%. Show less
Background. The radiation and concomitant high-dose intra-arterial or intravenous cisplatin (RADPLAT) phase III trial compared intra-arterial (IA) to intravenous (IV) cisplatin-based chemoradiation... Show moreBackground. The radiation and concomitant high-dose intra-arterial or intravenous cisplatin (RADPLAT) phase III trial compared intra-arterial (IA) to intravenous (IV) cisplatin-based chemoradiation for head and neck cancer. Long-term efficacy and toxicity are reported after a median follow-up of 7.5 years.Methods. Patients with inoperable squamous cell carcinoma (SCC) of the oropharynx, oral cavity, or hypopharynx, were randomized between radiotherapy (RT) + IA cisplatin 150 mg/m(2), followed by systemic rescue or RT + I. V. cisplatin 100 mg/m(2). RT consisted of 46 Gy to the affected and elective areas, followed by a boost of 24 Gy.Results. Among 237 patients, 57 recurred locally, 35 regionally, and 80 locoregionally. There were 32 second primary tumors, 65 distant metastases, and 154 deaths. Locoregional control and overall survival were not different between the treatment arms. Late dysphagia was worse in the I.V. arm (log-rank p=.014).Conclusion. IA cisplatin did not improve tumor control compared to I.V. administered cisplatin, despite the higher dose in IA delivery of the drug. (C) 2015 Wiley Periodicals, Inc. Show less
Theunissen, E.A.R.; Bosma, S.C.J.; Zuur, C.L.; Spijker, R.; Baan, S. van der; Dreschler, W.A.; ... ; Rasch, C.R.N. 2015
BackgroundBoth radiotherapy (RT) and cisplatin-based chemoradiotherapy (CRT) in patients with head and neck cancer may cause sensorineural hearing loss (SNHL). The purpose of this review was to... Show moreBackgroundBoth radiotherapy (RT) and cisplatin-based chemoradiotherapy (CRT) in patients with head and neck cancer may cause sensorineural hearing loss (SNHL). The purpose of this review was to provide more insight into SNHL because of CRT compared to RT.MethodsComprehensive search of Medline and Embase with the terms radiotherapy combined with ototoxicity, head and neck squamous cell carcinoma, and synonyms.ResultsOf the 2507 studies found, 21 were included in this study. Pooled analysis could not be committed because of heterogeneity. Incidence rates of SNHL after RT and CRT varied considerably, with percentages ranging from 0% to 43% and 17% to 88%, respectively. Factors that influenced the risk of SNHL were radiation dose to the cochlea, follow-up time, age, baseline hearing level, and cisplatin dose.ConclusionThe wide range of SNHL incidence rates makes it impossible to draw any conclusions on the severity of RT- and CRT-induced ototoxicity. To allow for future comparison of study outcomes, development of uniform criteria is of utmost importance. (c) 2014 Wiley Periodicals, Inc. Head Neck37: 281-292, 2015 Show less
Theunissen, E.A.R.; Zuur, C.L.; Bosma, S.C.J.; Lopez-Yurda, M.; Hauptmann, M.; Baan, S. van der; ... ; Balm, A.J.M. 2014
Objectives/HypothesisThe purpose of this study was to determine whether concomitant chemoradiation (CCRT)-induced hearing loss is progressive over time or not.Study DesignLong-term (LT) follow-up... Show moreObjectives/HypothesisThe purpose of this study was to determine whether concomitant chemoradiation (CCRT)-induced hearing loss is progressive over time or not.Study DesignLong-term (LT) follow-up study.MethodsBetween 1999 and 2004, 158 patients with head and neck cancer were treated with intravenous (IV) CCRT (n=80) or intraarterial CCRT (n=78). Audiometry was performed before, short-term (ST), and LT posttreatment. Differences in hearing were assessed with a multivariable linear regression analysis, incorporating the effect of aging.ResultsLong-term audiometry (median 4.5 years) was available in 67 patients (42%). At ST follow-up, a deterioration of 21.6 decibel was seen compared to baseline at pure-tone averages (PTA) 8-10-12.5 kHz. At LT follow-up, this deterioration further increased with 5 decibel (P = 0.005). Only in CCRT-IV patients was a significant progressive treatment-induced hearing loss seen, at PTA 8-10-12.5 kHz (P = 0.005), PTA 1-2-4 kHz air conduction (P = 0.014), and PTA 0.5-1-2 kHz bone conduction (P = 0.045).ConclusionCCRT-induced hearing impairment was progressive over time, especially in higher frequencies and only in CCRT-IV patients, with a modest deterioration of 5 decibel 4.5 years post-treatment.Level of Evidence4. Laryngoscope, 124:2720-2725, 2014 Show less
Mencarelli, A.; Beek, S. van; Kranen, S. van; Rasch, C.; Herk, M. van; Sonke, J.J. 2012
Purpose: Deformable image registration (DIR) is often validated based on a distance-to-agreement (DTA) criterion of automatically propagated anatomical landmarks that were manually identified. Due... Show morePurpose: Deformable image registration (DIR) is often validated based on a distance-to-agreement (DTA) criterion of automatically propagated anatomical landmarks that were manually identified. Due to human observer variability, however, the performance of the registration method is diluted. The purpose of this study was to evaluate an analysis of variance (ANOVA) based validation to account for such observer variation.Methods: Weekly cone beam CTs (CBCTs) of ten head and neck cancer patients undergoing five weeks of radiotherapy were used. An expert identified 23 anatomical features (landmarks) on the planning CT. The landmarks were automatically propagated to the CBCT using multiregion-of-interest (mROI) registration. Additionally, two human observers independently localized these landmarks on the CBCTs. Subsequently, ANOVA was used to compute the variance of each observer on the pairwise distance (PWD).Results: ANOVA based analysis demonstrated that a classical DTA approach underestimated the precision for the mROI due to human observer variation by about 25%. The systematic error (accuracy) of mROI ranged from 0.13 to 0.17 mm; the variability (1 SD) (precision) ranged from 1.3 to 1.5 mm demonstrating that its performance is dominated by the precision.Conclusions: The PWD-ANOVA method accounts for human observer variation allowing a better estimation of the of DIR errors. c 2012 American Association of Physicists in Medicine. [http://dx.doi.org/10.1118/1.4760990] Show less
Background: Concomitant chemo-radiotherapy (CCRT) has become an indispensable organ, but not always function preserving treatment modality for advanced head and neck cancer. To prevent/limit the... Show moreBackground: Concomitant chemo-radiotherapy (CCRT) has become an indispensable organ, but not always function preserving treatment modality for advanced head and neck cancer. To prevent/limit the functional side effects of CCRT, special exercise programs are increasingly explored. This study presents cost-effectiveness analyses of a preventive (swallowing) exercise program (PREP) compared to usual care (UC) from a health care perspective.Methods: A Markov decision model of PREP versus UC was developed for CCRT in advanced head and neck cancer. Main outcome variables were tube dependency at one-year and number of post-CCRT hospital admission days. Primary outcome was costs per quality adjusted life years (cost/QALY), with an incremental cost-effectiveness ratio (ICER) as outcome parameter. The Expected Value of Perfect Information (EVPI) was calculated to obtain the value of further research.Results: PREP resulted in less tube dependency (3% and 25%, respectively), and in fewer hospital admission days than UC (3.2 and 4.5 days respectively). Total costs for UC amounted to (sic)41,986 and for PREP to (sic)42,271. Quality adjusted life years for UC amounted to 0.68 and for PREP to 0.77. Based on costs per QALY, PREP has a higher probability of being cost-effective as long as the willingness to pay threshold for 1 additional QALY is at least (sic)3,200/QALY. At the prevailing threshold of (sic)20,000/QALY the probability for PREP being cost-effective compared to UC was 83%. The EVPI demonstrated potential value in undertaking additional research to reduce the existing decision uncertainty.Conclusions: Based on current evidence, PREP for CCRT in advanced head and neck cancer has the higher probability of being cost-effective when compared to UC. Moreover, the majority of sensitivity analyses produced ICERs that are well below the prevailing willingness to pay threshold for an additional QALY (range from dominance till (sic)45,906/QALY). Show less
Knegjens, J.L.; Hauptmann, M.; Pameijer, F.A.; Balm, A.J.; Hoebers, F.J.; Bois, J.A. de; ... ; Rasch, C.R. 2011
Background. Tumor volume is an important predictor of outcome in radiotherapy alone. Its significance in concomitant chemoradiation (CCRT) is much less clear. We analyzed the prognostic value of... Show moreBackground. Tumor volume is an important predictor of outcome in radiotherapy alone. Its significance in concomitant chemoradiation (CCRT) is much less clear. We analyzed the prognostic value of primary tumor volume for advanced head and neck squamous cell carcinoma (HNSCC) treated with CCRT.Methods. Three hundred sixty patients treated with definitive CCRT for advanced HNSCC were selected. The pretreatment MRI or CT scan was used to calculate the primary tumor volume. Median follow-up was 19.8 months.Results. The average primary tumor volume was 37.0 cm(3) (range, 2.1-182.7 cm(3); median, 28.7 cm(3)). Multivariate analysis showed a significant effect of tumor volume on local control. The hazard ratio for a local recurrence increased by 14% per 10 cm(3) volume increase (95% CI, 8% to 21%). There was no significant independent effect of T and N status on local control.Conclusion. For advanced HNSCC, tumor volume is more powerful for predicting outcome after CCRT than TNM status. (C) 2010 Wiley Periodicals, Inc. Head Neck 33: 375-382, 2011 Show less
BACKGROUND: Chemoradiation is the preferred treatment for advanced stage IV head and neck cancer. Higher doses of chemotherapy yielded promising results in vitro and vivo, confirmed by intra... Show moreBACKGROUND: Chemoradiation is the preferred treatment for advanced stage IV head and neck cancer. Higher doses of chemotherapy yielded promising results in vitro and vivo, confirmed by intra-arterial (IA) cisplatin-based chemoradiation in phase 2 studies. METHODS: Two hundred and thirty-nine patients with (functionally) unresectable head and neck cancer were included, from 2000 to 2004, in a multicenter, randomized phase 3 trial, comparing IA and intravenous chemoradiation. Intravenous chemoradiation comprised 3x100 mg/m(2) cisplatin infusion on Days 1, 22, 43 combined with 70 Gy in 35 daily fractions. The IA chemoradiation treatment arm comprised 4x150 mg/m2 cisplatin administered in the tumor-feeding artery on Days 1, 8, 15, 22, immediately followed by systemic rescue with sodium thiosulfate with the same radiotherapeutic regimen. RESULTS: Two patients were excluded from analysis because of nontreatment-related death immediately after randomization (n=1) and esophageal carcinoma (n=1). The median follow-up was 33 months 1-104 months. Ninety percent of the patients required tube feeding during treatment. Renal toxicity >grade 2 was 9% in the intravenous compared with 1% in the IA treatment arm (P <= .0001). There was no difference in locoregional control, disease-free survival (DFS) or overall survival (OS), between the treatment arms. At 3 years, local control, locoregional control, DFS, and OS was .76, .63, .44, .51 in the IA versus .70, .65, .47, .47 in the intravenous treatment arm, respectively. CONCLUSIONS: Cisplatin-based IA chemoradiation was not superior to intravenous chemoradiation for advanced stage IV head and neck cancer regarding locoregional control and survival. Cancer 2010;116:2159-65. (C) 2010 American Cancer Society. Show less
