A multicentric randomized controlled phase III trial of adaptive and 18F-FDG-PET-guided dose-redistribution in locally advanced head and neck squamous cell carcinoma (ARTFORCE).

BACKGROUND AND PURPOSE: This multicenter randomized phase III trial evaluated whether locoregional control of patients with LAHNSCC could be improved by fluorodeoxyglucose-positron emission tomography (FDG-PET)-guided dose-escalation while minimizing the risk of increasing toxicity using a dose-redistribution and scheduled adaptation strategy. MATERIALS AND METHODS: Patients with T3-4-N0-3-M0 LAHNSCC were randomly assigned (1:1) to either receive a dose distribution ranging from 64-84 Gy/35 fractions with adaptation at the 10thfraction (rRT) or conventional 70 Gy/35 fractions (cRT). Both arms received concurrent three-cycle 100 mg/m2cisplatin. Primary endpoints were 2-year locoregional control (LRC) and toxicity. Primary analysis was based on the intention-to-treat principle. RESULTS: Due to slow accrual, the study was prematurely closed (at 84 %) after randomizing 221 eligible patients between 2012 and 2019 to receive rRT (N = 109) or cRT (N = 112). The 2-year LRC estimate difference of 81 % (95 %CI 74-89 %) vs. 74 % (66-83 %) in the rRT and cRT arm, respectively, was not found statistically significant (HR 0.75, 95 %CI 0.43-1.31,P=.31). Toxicity prevalence and incidence rates were similar between trial arms, with exception for a significant increased grade ≥ 3 pharyngolaryngeal stenoses incidence rate in the rRT arm (0 versus 4 %,P=.05). In post-hoc subgroup analyses, rRT improved LRC for patients with N0-1 disease (HR 0.21, 95 %CI 0.05-0.93) and oropharyngeal cancer (0.31, 0.10-0.95), regardless of HPV. CONCLUSION: Adaptive and dose redistributed radiotherapy enabled dose-escalation with similar toxicity rates compared to conventional radiotherapy. While FDG-PET-guided dose-escalation did overall not lead to significant tumor control or survival improvements, post-hoc results showed improved locoregional control for patients with N0-1 disease or oropharyngeal cancer treated with rRT.

Long-term outcomes, quality of life, and costs of treatment modalities for T1-T2 lip carcinomas.

PURPOSE: Early stage lip squamous cell carcinoma (lip SCC) can be treated with conventional excision, Mohs micrographic surgery (MMS), or brachytherapy. The aim of this retrospective study was to describe the medical outcomes, patient-reported outcomes, and costs of these treatments. METHODS: A retrospective cohort study of T1-T2 lip SSCs treated between 1996 and 2019. Medical outcomes, recurrences, and survival were retrieved from medical records. Facial appearance, facial function, and Quality of Life (QoL) were measured with the Face-Q H&N and EQ-5D-5L questionnaires. Costs were also calculated. RESULTS: Of the 336 lip SCCs, 122 were treated with excision, 139 with MMS, and 75 with brachytherapy. Locally, the recurrence rate was 2.7% and regionally 4.8%. There were 2% disease-related deaths. T2-stage and poor tumor differentiation were associated with recurrences. Posttreatment QoL, facial function, and appearance were rated as good. Brachytherapy was the most expensive treatment modality. CONCLUSION: Early-stage lip SCC has a good prognosis, with a disease-specific survival of 98.2% after a median follow-up of 36 months, there was a high QoL and satisfaction at long-term follow-up. Based on the costs and the risk of locoregional recurrences, we believe that, for most noncomplex lip SCCs, MMS would be the most logical treatment option.

Longitudinal Patient-Reported Voice Quality in Early-Stage Glottic Cancer.

OBJECTIVE: Patient-reported voice quality is an important outcome during counseling in early-stage glottic cancer. However, there is a paucity of adequate longitudinal studies concerning voice outcomes. This study aimed to investigate longitudinal trajectories for patient-reported voice quality and associated risk factors for treatment modalities such as transoral CO2 laser microsurgery, single vocal cord irradiation, and local radiotherapy. STUDY DESIGN: A longitudinal observational cohort study. SETTING: Tertiary cancer center. METHODS: Patients treated for Tcis-T1b, N0M0 glottic cancer were included in this study (N = 294). The Voice Handicap Index was obtained at baseline and during follow-up (N = 1944). Mixed-effects models were used for investigating the different trajectories for patient-reported voice quality. RESULTS: The mean follow-up duration was 43.4 (SD 21.5) months. Patients received transoral CO2 laser microsurgery (57.8%), single vocal cord irradiation (24.5%), or local radiotherapy (17.5%). A steeper improvement during the first year after treatment for single vocal cord irradiation (-15.7) and local radiotherapy (-12.4) was seen, compared with a more stable trajectory for laser surgery (-6.1). All treatment modalities showed equivalent outcomes during long-term follow-up. Associated risk factors for different longitudinal trajectories were age, tumor stage, and comorbidity. CONCLUSION: Longitudinal patient-reported voice quality after treatment for early-stage glottic cancer is heterogeneous and nonlinear. Most improvement is seen during the first year of follow-up and differs between treatment modalities. No clinically significant differences in long-term trajectories were found. Insight into longitudinal trajectories can enhance individual patient counseling and provide the foundation for an individualized dynamic prediction model.

Single vocal cord irradiation for early-stage glottic cancer: Excellent local control and favorable toxicity profile.

OBJECTIVE: To validate the earlier reported promising oncologic outcomes and favorable toxicity profile following single vocal cord irradiation (SVCI) in an expanded cohort of patients with early-stage glottic cancer treated at our institute with longer follow-up time. MATERIALS AND METHODS: Between February 2011 and January 2020, 111 consecutive patients with early-stage glottic cancer were treated with SVCI to the whole involved vocal cord (58.08 Gy, given in 16 fractions of 3.63 Gy). Setup verification was done using cone-beam CT, prior to each fraction. The endpoints were local control (LC), overall survival (OS), grade ≥ 3 toxicity and voice quality assessment using voice-handicap index (VHI) questionnaires. RESULTS: Median follow-up was 41 months (range; 8-84). Two patients developed in-field local failure (LF). The 3- and 5-year LC rates were 99.1% and 97.1%, respectively. As both patients with LF were successfully salvaged with total laryngectomy, the 5-year ultimate LC-rates was 99%. The 5-years OS was 80.6%. All patients finished treatment without any interruption. No patients developed acute grade ≥ 3 toxicity. Late grade 3 toxicity was reported in 7 patients (6.5%) out of 108 patients evaluable for late toxicity; 2 because of severe hoarseness and 5 because of laryngeal radionecrosis (4.5%). The 5-years laryngectomy-free survival was 98.1%. The VHI-scores improved over time, only 22% of patients had VHI > 30 at 3-years post-radiotherapy, compared to 38% at baseline. CONCLUSIONS: Local control rate and laryngectomy-free survival of SVCI are excellent with favorable toxicity profile and good VHI-score. These results validate our early results.

Postoperative radiotherapy in stage I-III Merkel cell carcinoma.

BACKGROUND: Postoperative radiotherapy (PORT) is currently recommended for the treatment of Merkel cell carcinoma. Nevertheless, deviations occur frequently due to the generally elderly and frail patient population. We aimed to evaluate the influence of PORT on survival in stage I-III MCC patients treated in the Netherlands. METHODS: Patients were included retrospectively between 2013 and 2018. Fine-Gray method was used for cumulative incidence of recurrence and MCC-related death, cox regression was performed for overall mortality. Analyses were performed in patients with clinical (sentinel node biopsy [SN] not performed) stage I/II (c-I/II-MCC), pathologic (SN negative) stage I/II (p-I/II-MCC) and stage III MCC (III-MCC), separately. Propensity score matching (PSM) was performed to assess confounding by indication. RESULTS: In total 182 patients were included, 35 had p-I/II-MCC, 69 had c-I/II-MCC and 78 had III-MCC. Median follow up time was 53.5 (IQR 33.4-67.4), 30.5 (13.0-43.6) and 29.3 (19.3-51.0) months, respectively. Multivariable analysis showed PORT to be associated with less recurrences and reduced overall mortality, but not with MCC-related mortality. In stage III-MCC, extracapsular extension (sub-distribution hazard [SDH] 4.09, p = 0.012) and PORT (SDH 0.45, p = 0.044) were associated with recurrence, and ≥ 4 positive lymph nodes (SDH 3.24, p = 0.024) were associated with MCC-related mortality. CONCLUSIONS: PORT was associated with less recurrences and reduced overall mortality in patients with stage I-III MCC, but not with MCC-related mortality. Trends in overall survival benefit are likely to be caused by selection bias suggesting further refinement of criteria for PORT is warranted, for instance by taking life expectancy into account.

Randomized controlled trial to identify the optimal radiotherapy scheme for palliative treatment of incurable head and neck squamous cell carcinoma.

BACKGROUND: No randomized controlled trials (RCT) have yet identified the optimal palliative radiotherapy scheme in patients with incurable head and neck squamous cell carcinoma (HNSCC). We conducted RCT to compare two radiation schemes in terms of efficacy, toxicity and quality-of-life (QoL). MATERIALS AND METHODS: Patients with locally-advanced HNSCC who were ineligible for radical treatment and those with limited metastatic disease were randomly assigned in 1:1 ratio to arm 1 (36 Gy in 6 fractions, twice a week) or arm 2 (50 Gy in 16 fractions, four times a week). RESULTS: The trial was discontinued early because of slow accrual (34 patients enrolled). Objective response rates were 38.9% and 57.1% for arm 1 and 2 respectively (p = 0.476). The median time to loco-regional progression was not reached. The loco-regional control rates at 1 year was 57.4% and 69.3% in arm 1 and 2 (p = 0.450, HR = 0.56, 95%CI 0.12-2.58). One-year overall survival was 33.3% and 57.1%, with medians of 35.4 and 59.5 weeks, respectively (p = 0.215, HR = 0.55, 95%CI 0.21-1.43). Acute grade ≥3 toxicity was lower in arm 1 (16.7% versus 57.1%, p = 0.027), with the largest difference in grade 3 mucositis (5.6% versus 42.9%, p = 0.027). However, no significant deterioration in any of the patient-reported QoL-scales was found. CONCLUSION: No solid conclusion could be made on this incomplete study which is closed early. Long-course radiotherapy did not show significantly better oncologic outcomes, but was associated with more acute grade 3 mucositis. No meaningful differences in QoL-scores were found. Therefore, the shorter schedule might be carefully advocated. However, this recommendation should be interpreted with great caution because of the inadequate statistical power.

The impact of treatment accuracy on proton therapy patient selection for oropharyngeal cancer patients.

BACKGROUND AND PURPOSE: The impact of treatment accuracy on NTCP-based patient selection for proton therapy is currently unknown. This study investigates this impact for oropharyngeal cancer patients. MATERIALS AND METHODS: Data of 78 patients was used to automatically generate treatment plans for a simultaneously integrated boost prescribing 70 GyRBE/54.25 GyRBE in 35 fractions. IMRT treatment plans were generated with three different margins; intensity modulated proton therapy (IMPT) plans for five different setup and range robustness settings. Four NTCP models were evaluated. Patients were selected for proton therapy if NTCP reduction was ≥10% or ≥5% for grade II or III complications, respectively. RESULTS: The degree of robustness had little impact on patient selection for tube feeding dependence, while the margin had. For other complications the impact of the robustness setting was noticeably higher. For high-precision IMRT (3 mm margin) and high-precision IMPT (3 mm setup/3% range error), most patients were selected for proton therapy based on problems swallowing solid food (51.3%) followed by tube feeding dependence (37.2%), decreased parotid flow (29.5%), and patient-rated xerostomia (7.7%). CONCLUSIONS: Treatment accuracy has a significant impact on the number of patients selected for proton therapy. Therefore, it cannot be ignored in estimating the number of patients for proton therapy.

Single Vocal Cord Irradiation: Image Guided Intensity Modulated Hypofractionated Radiation Therapy for T1a Glottic Cancer: Early Clinical Results.

PURPOSE: To report, from a retrospective analysis of prospectively collected data, on the feasibility, outcome, toxicity, and voice-handicap index (VHI) of patients with T1a glottic cancer treated by a novel intensity modulated radiation therapy technique developed at our institution to treat only the involved vocal cord: single vocal cord irradiation (SVCI). METHODS AND MATERIALS: Thirty patients with T1a glottic cancer were treated by means of SVCI. Dose prescription was set to 16 × 3.63 Gy (total dose 58.08 Gy). The clinical target volume was the entire vocal cord. Setup verification was done by means of an online correction protocol using cone beam computed tomography. Data for voice quality assessment were collected prospectively at baseline, end of treatment, and 4, 6, and 12 weeks and 6, 12, and 18 months after treatment using VHI questionnaires. RESULTS: After a median follow-up of 30 months (range, 7-50 months), the 2-year local control and overall survival rates were 100% and 90% because no single local recurrence was reported and 3 patients died because of comorbidity. All patients have completed the intended treatment schedule; no treatment interruptions and no grade 3 acute toxicity were reported. Grade 2 acute dermatitis or dysphagia was reported in only 5 patients (17%). No serious late toxicity was reported; only 1 patient developed temporary grade 2 laryngeal edema, and responded to a short-course of corticosteroid. The VHI improved significantly, from 33.5 at baseline to 9.5 and 10 at 6 weeks and 18 months, respectively (P<.001). The control group, treated to the whole larynx, had comparable local control rates (92.2% vs 100%, P=.24) but more acute toxicity (66% vs 17%, P<.0001) and higher VHI scores (23.8 and 16.7 at 6 weeks and 18 months, respectively, P<.0001). CONCLUSION: Single vocal cord irradiation is feasible and resulted in maximal local control rate at 2 years. The deterioration in VHI scores was slight and temporary and subsequently improved to normal levels. Long-term follow-up is needed to consolidate these promising results.

Radiotherapy for T1a glottic cancer: the influence of smoking cessation and fractionation schedule of radiotherapy.

The objective of the presented study is to report on retrospectively collected data on long-term outcome and toxicity and prospective assessment of quality of life (QoL) and Voice-Handicap Index (VHI) of patients with T1a glottic cancer treated with radiotherapy. Between 1985 and 2011, 549 patients were treated. Endpoints were local control (LC), toxicity, QoL and VHI. After a median follow-up of 93 months, the actuarial rates of LC were 91, and 90 % at 5- and 10-years, respectively. Continuing smoking (p < 0.001) and anaemia (p = 0.02) were significantly correlated with poor LC on univariate analysis and fractionation schedule did not show significant correlation (p = 0.08). On multivariate analysis, only continuing smoking retained significance (p = 0.001). These patients had also significantly increased incidence of second primary tumour and lower overall survival rates. The incidence of grade ≥2 late xerostomia and dysphagia were 10 and 6 %, respectively. Slight and temporary deterioration of QoL-scores was reported. The scores on the EROTC-QOL-H&N35 dysphagia and xerostomia at 24 months were -2 and -3, compared to baseline, respectively. VHI improved significantly from 34 at baseline to 21 at 24 months. Patients who continued smoking had significantly worse VHI. In conclusion, excellent outcome with good QoL and VHI were reported. Patients who continued smoking after radiotherapy had significantly poor LC and worse VHI. The current study emphasizes the importance of smoking cessation and the non-inferiority of hypofractionated schemes in terms of outcome and VHI. At our institution, phase II study is going to evaluate the role of single vocal cord irradiation with high fraction dose.

Brachytherapy or stereotactic body radiotherapy boost for early-stage oropharyngeal cancer: comparable outcomes of two different approaches.

OBJECTIVES: To compare outcome, toxicity and QoL of two boost modalities for T1-2 oropharyngeal carcinoma (OPC). MATERIALS AND METHODS: Between 2000 and 2012, 250 consecutive patients with T1-2N0-3 were treated with 46-Gy of IMRT followed by boost using brachytherapy (BTB) or stereotactic body radiotherapy (CKB). Endpoints were local control (LC), disease-free survival (DFS), overall survival (OS), toxicity and prospective QoL-assessment. RESULTS: The 3-year actuarial incidence of LC were 97% and 94% for the CKB and BTB, respectively (p=0.33). The figures for DFS were 92% and 86% (p=0.15) and for OS were 81% and 83% (p=0.82), respectively. The incidence of tube feeding were 17% and 20%, respectively (p=0.47). The figures for grade ⩾2 late dysphagia were 11% and 8% (p=0.34) and for xerostomia were 16% and 12% (p=0.28), respectively. For both modalities, clinically relevant deteriorations were seen on all scales at end of treatment but the scores returned to almost baseline levels within 6-12months, with exception of QLQ-H&N35-xerostomia. The difference on that scale was neither statistically significant nor clinically relevant between both modalities. CONCLUSION: Comparable outcome, toxicity and QoL-scores were achieved with both modalities. In the light of the logistical hassle around the implantation, the need of dexterity, and the risk of anaesthesia and peri-operative complications associated with BTB, CKB might be regarded as the optimal option to boost early-stage OPC. However, in radiotherapy departments where no facilities are available for stereotactic radiotherapy, BTB is an elegant option to achieve excellent outcome with low toxicity profile and good QoL.

A prospective evaluation of patient-reported quality-of-life after (chemo)radiation for oropharyngeal cancer: which patients are at risk of significant quality-of-life deterioration?

BACKGROUND AND PURPOSE: To prospectively investigate the impact of different patients' characteristics on quality-of-life (QoL) after (chemo)radiation for oropharyngeal cancer (OPC). MATERIALS AND METHODS: Between 2008 and 2011, 207 patients were treated with 46-Gy of (chemo)-IMRT followed by a boost by means of IMRT, brachytherapy (BT), or Cyberknife (CK). QoL-assessment was performed using the EORTC QLQ-C30, and QLQ-H&N35-questionnaires at baseline, end of treatment, 2, 4, 6 weeks and 3, 6, 12, and 18 months after treatment. The correlation between patients' characteristics (AJCC-stage, tumor subsite, chemotherapy, neck dissection, unilateral neck irradiation, and boost technique), and changes in QoL over time were investigated. RESULTS: At 18months, improvements were seen in QLQ-C30 emotional functioning, insomnia, and pain and QLQ-H&N35 pain and speech. The scores on QLQ-H&N35 swallowing returned to baseline level while the scores on dry mouth, sticky saliva, opening mouth, and teeth were significantly deteriorated compared to baseline. Boost techniques and unilateral neck irradiation were significantly predictive for dry mouth, swallowing and opening mouth while chemotherapy was correlated with changes on swallowing and opening mouth scales. CONCLUSIONS: The most significant deterioration was seen in patient-related xerostomia. Boost technique, unilateral neck irradiation and chemotherapy were significantly predictive for QoL-changes over time.

Combined-modality treatment improved outcome in sinonasal undifferentiated carcinoma: single-institutional experience of 21 patients and review of the literature.

The optimal treatment of sinonasal undifferentiated carcinoma (SNUC) remains unclear. We report our results on the outcome and toxicity of patients with SNUC treated by a combined modality and attempt to define the optimal treatment strategies by reviewing the literature. Between 1996 and 2010, 21 consecutive patients with SNUC were treated by any combination of surgery, chemotherapy and radiotherapy. End points were local control (LC), regional control (RC), disease-free (DFS), cause-specific (CSS) overall survival (OS), and late toxicity. Organ preservation was defined as visual preservation without orbital exenteration. After median follow-up of 54 months, the 5-year actuarial rates of LC, RC, DFS, CSS, and OS were 80, 90, 64, 74, and 74 % respectively. On multivariate analysis, T-stage and multimodality treatment approach correlated significantly with LC. Elective nodal irradiation was given to 42 % of high-risk node-negative patients. None of them developed regional failure. The overall 5-year incidence of grade ≥ 2 late toxicity was 30 %. Treatment-related blindness was significantly decreased in patients treated with intensity-modulated radiotherapy (IMRT), compared to 2D and 3D-conformal radiotherapy (3DCRT), with organ preservation rates of 86 and 14 % respectively (p = 0.006). We concluded that combined-modality treatment with three, or at least two, modalities resulted in good LC, but with high overall rate of late toxicity. However, the incidence of late toxicity and permanent visual impairment were decreased over time by the introduction of IMRT. Because of the improvement in therapeutic ratio achieved by using IMRT, this highly conformal radiation technique should be the standard of care in patients with SNUC.

Toxicity and outcome of intensity-modulated radiotherapy versus 3-dimensional conformal radiotherapy for oropharyngeal cancer: a matched-pair analysis.

Because of the scarcity of randomized trials comparing toxicity and outcomes of intensity-modulated radiotherapy (IMRT) for oropharyngeal cancer (OPC) with 3D-conformal radiotherapy (3DCRT), we performed a matched-pair analysis from prospectively collected data from the Head and Neck Tumor Registry of our institution. In the absence of phase III trials, we believe this approach provides the highest quality data possible. Ninety-two patients treated with 3DCRT were matched (1:1) to 92 patients treated with IMRT for 9 potential predictive factors for toxicity and outcome: gender, age, T-stage, N-stage, tumor subsite, unilateral neck irradiation, chemotherapy, neck dissection and boost technique. Groups were compared for acute and late toxicity, locoregional control (LRC), disease-free survival (DFS), and overall survival (OS). Oncologic outcomes were estimated using Kaplan-Meier analyses and toxicity was analyzed according to Common Terminology Criteria for Adverse Events v3.0. The overall incidence of grade 3 acute toxicity was significantly reduced by IMRT, compared to 3DCRT (45% vs. 70%, p = 0.001). The need for tube feeding was reduced from 50% to 37% (p = 0.04). The 3-year actuarial incidence of grade ≥2 late toxicity was also significantly reduced by IMRT, compared to 3DCRT (20% vs. 45%, respectively; p ≤ 0.0001). The incidence of grade ≥ 2 late dysphagia and xerostomia for IMRT vs. 3DCRT were 10% vs. 31% for dysphagia, p = 0.004 and 13% vs. 37%, for xerostomia, respectively (p = 0.001). The 3-year Kaplan-Meier estimates of LRC, DFS, and OS for IMRT vs. 3DCRT were 90% vs. 82% (p = 0.1), 82% vs. 76% (p = 0.3), and 72% vs. 64% (p = 0.2), respectively. In conclusion, the presented non-randomized comparative study of well-matched groups demonstrates the superiority of IMRT vs. 3DCRT for OPC by significantly reducing radiation-induced toxicity without jeopardizing outcomes. The improved therapeutic ratio achieved by the use of IMRT would allow dose escalation of radiotherapy to further improve outcomes of patients with OPC.

Toxicity, quality of life, and functional outcomes of 176 hypopharyngeal cancer patients treated by (chemo)radiation: the impact of treatment modality and radiation technique.

OBJECTIVES/HYPOTHESIS: The main goal of the current study was to comprehensively address the impact of chemoradiation and radiation techniques on toxicity, quality of life (QoL), and functional outcome. STUDY DESIGN: Retrospective analysis of toxicity and functional outcome and prospective QoL assessment. METHODS: From 1996 to 2010, 176 consecutive patients with hypopharyngeal cancer (HPC) were treated with (chemo)radiotherapy. End points were acute and late toxicity, QoL assessment, and functional outcome using laryngoesophageal dysfunction-free survival (LED-FS) defined by the Laryngeal Preservation Consensus Panel. RESULTS: Chemoradiation significantly increased grade 3 acute toxicity compared to radiotherapy alone (71% vs. 55%, P = .02). The 3-year grade ≥2 late toxicity was 32%. Intensity-modulated radiotherapy (IMRT) significantly reduced late toxicity compared to three-dimensional conformal radiotherapy (3DCRT) (24% vs. 44%, P = .007). Slight deterioration in QoL scores was observed on almost all scales, and was more pronounced in patients treated with chemoradiation, albeit not statistically significant except for xerostomia. Chemoradiation, compared to radiotherapy alone, improved LED-FS at 3 years (51% vs. 24% for the entire group and 83% vs. 63% for the 78 living patients at last follow-up, respectively [P = .05]). CONCLUSIONS: Compared to radiotherapy alone, chemoradiation significantly improved functional outcome, increased acute toxicity, but without significant increase in late radiation-induced side effects. Statistically significant deterioration in QoL scores was reported only for xerostomia. IMRT, compared to 3DCRT, reduced the incidence and severity of acute and late toxicity, thereby broadening the therapeutic window, and may allow dose escalation for further improvement of outcomes of laryngeal preservation protocols.

Adenoid cystic carcinoma of parotid gland treated with surgery and radiotherapy: long-term outcomes, QoL assessment and review of the literature.

To assess outcomes, toxicity and quality-of-life (QoL) of patients with parotid gland adenoid cystic carcinoma (PGACC) treated by surgery and postoperative radiotherapy. Between 1995 and 2010, 46 patients with PGACC were treated with parotidectomy±neck dissection followed by radiotherapy. Endpoints were loco-regional control (LRC), distant metastasis-free (DMFS), disease-free (DFS), cause-specific (CSS), and overall survival (OS), late toxicity, and QoL. After a median follow-up of 58 months (range 4-171), the 5-year Kaplan-Meier estimates of LRC, DMFS, DFS, CSS, and OS were 88%, 78%, 75%, 80%, and 67%, respectively and the 8-year rates were 88%, 75%, 72%, 77%, and 64%, respectively. On multivariate analysis, T-stage, N-stage, tumor grade, and perineural invasion correlate significantly with DMFS and DFS. The overall 5-year cumulative incidence of grade ≥2 late toxicity was 9%. QoL-scores deteriorate during and shortly after treatment but returned in all scales to almost baseline levels within 6 months. Excellent LRC rates were achieved in patients with PGACC treated by surgery and postoperative radiotherapy with low rate of late side-effects and preservation of good QoL. Despite the effective local therapy, 9 of 46 patients (20%) failed distantly. Because effective treatment strategies for this problem are lacking, prospective trials are needed to determine the role of adjuvant systemic or targeted therapy in patients at high risk of DM.

A single-institutional experience of 15 years of treating T3 laryngeal cancer with primary radiotherapy, with or without chemotherapy.

PURPOSE: To retrospectively analyze the outcomes, toxicity, quality of life, and voice quality of patients with T3 laryngeal cancer treated with radiotherapy and to identify subgroups of patients in whom the addition of chemotherapy to radiotherapy is necessary. METHODS AND MATERIALS: Between March 1996 and November 2009, 170 consecutive patients with T3 tumor were treated with (chemo)radiotherapy. Endpoints of the study were local control (LC), locoregional control (LRC), disease-free survival (DFS), overall survival (OS), late toxicity, quality of life, and voice handicap index. RESULTS: After a median follow-up time of 32 months (range, 7-172), the 3-year actuarial rates of LC, LRC, DFS, and OS were 73%, 70%, 64%, and 61%, respectively, and the 5-year figures were 68%, 65%, 60%, and 49%, respectively. At last follow-up, 84 patients (49.5%) were still alive, 65 of them (77.3%) without local progression. Laryngectomy was performed in 16 patients, leaving 49 patients with anatomic organ preservation, corresponding to an actuarial laryngectomy-free survival of 58.3% at 3 years. The figures for patients treated with chemoradiotherapy and radiotherapy alone were 76.8% and 53.5%, respectively (p = 0.001). Chemoradiotherapy was the only significant predictor for LC on multivariate analysis. The overall 5-year cumulative incidence of late Grade ≥2 toxicity was 28.2%. Chemoradiotherapy, compared with radiotherapy alone, resulted in slight increase in late toxicity and slight deterioration of quality of life and voice-handicap-index scores. However, the differences were statistically not significant. CONCLUSION: The addition of chemotherapy to radiotherapy in T3 laryngeal cancer significantly improved LC and laryngectomy-free survival without statistically significant increases in late toxicity or deterioration of quality of life or voice handicap index.

Stereotactic body radiotherapy: a promising treatment option for the boost of oropharyngeal cancers not suitable for brachytherapy: a single-institutional experience.

PURPOSE: To prospectively assess the outcome and toxicity of frameless stereotactic body radiotherapy (SBRT) as a treatment option for boosting primary oropharyngeal cancers (OPC) in patients who not suitable for the standard brachytherapy boost (BTB). METHODS AND MATERIALS: Between 2005 and 2010, 51 patients with Stage I to IV biopsy-proven OPC who were not suitable for BTB received boosts by means of SBRT (3 times 5.5 Gy, prescribed to the 80% isodose line), after 46 Gy of IMRT to the primary tumor and neck (when indicated). Endpoints of the study were local control (LC), disease-free survival (DFS), overall survival (OS), and acute and late toxicity. RESULTS: After a median follow-up of 18 months (range, 6-65 months), the 2-year actuarial rates of LC, DFS, and OS were 86%, 80%, and 82%, respectively, and the 3-year rates were 70%, 66%, and 54%, respectively. The treatment was well tolerated, as there were no treatment breaks and no Grade 4 or 5 toxicity reported, either acute or chronic. The overall 2-year cumulative incidence of Grade ≥2 late toxicity was 28%. Of the patients with 2 years with no evidence of disease (n = 20), only 1 patient was still feeding tube dependent and 2 patients had Grade 3 xerostomia. CONCLUSIONS: According to our knowledge, this study is the first report of patients with primary OPC who received boosts by means of SBRT. Patients with OPC who are not suitable for the standard BTB can safely and effectively receive boosts by SBRT. With this radiation technique, an excellent outcome was achieved. Furthermore, the SBRT boost did not have a negative impact regarding acute and late side effects.

The role of chemo-radiotherapy in the management of locally advanced carcinoma of the vulva: single institutional experience and review of literature.

OBJECTIVE: To retrospectively investigate the outcome and toxicity of concurrent chemo-radiotherapy in the treatment of locally advanced vulvar cancer (LAVC). PATIENTS AND METHODS: Between 1996 and 2007, 28 consecutive patients with LAVC were treated with chemoradiation (20 primary tumors and 8 loco-regional recurrences). Treatment consists of 2 separate courses of external-beam radiotherapy (40 Gy-2 weeks split-20 Gy). During each course of radiotherapy, 5-fluorouracil (1000 mg/m/d), was given as a continuous intravenous infusion over the first 4 days, and mitomycin-C (10 mg/m on day 1), as a bolus intravenous injection. Outcome measures were rates of complete and partial response, loco-regional control, progression-free survival, overall survival, and toxicity. RESULTS: The median follow-up was 42 months and the median age of patients was 68 years. Twenty patients (72%) achieved complete remission, 4 patients (14%) partial remission, for an overall response rate of 86%. Four patients (14%) had progressive disease directly after chemo-radiotherapy. The actuarial rates of loco-regional control, progression-free survival and overall survival at 4 years were 75%, 71%, and 65%, respectively. There was no treatment break for acute toxicity. Vulvar desquamation was the main acute treatment-related side effect (93%). Three patients developed transient grade 2 neutropenia or thrombocytopenia. Mild skin fibrosis and atrophy (n = 6, 21%), radiation ulcer (n = 4, 14%, in one patient treatment was needed), telangectasia (n = 3, 11%), and lymphoedema (n = 2, 7%) were the most common late toxicity of chemoradiation. CONCLUSION: These data support the use of concurrent chemoradiotherapy as an effective alternative to primary ultra-radical surgery to treat LAVC with an acceptable toxicity profile.

Controversies in the treatment of high-risk prostate cancer--what is the optimal combination of hormonal therapy and radiotherapy: a review of literature.

BACKGROUND: In high-risk prostate carcinoma, there is controversy whether these patients should be treated with escalated-dose (> or =74 Gy) or conventional-dose radiotherapy (<74 Gy) combined with hormonal therapy. Furthermore, the issue of the optimal duration and timing of hormonal therapy are not well crystallized. PATIENTS AND METHODS: A search for evidence from randomized- and large non-randomized studies in order to address these issues, was therefore initiated. For this purpose, MedLine, EMbase, and PubMed and the data base of the Dutch randomized dose-escalation trial, were consulted. RESULTS AND CONCLUSIONS: From this search it was concluded that the benefit of hormonal therapy in combination with conventional-dose radiotherapy (<74 Gy) in high-risk prostate cancer is evident (Level 2 evidence); Levels 2 and 3 evidence were provided by several studies supporting the use of escalated-dose radiotherapy in high-risk prostate cancer. For the combination of hormonal therapy with escalated-dose radiotherapy in these patients, there is Level 2 evidence for moderately escalated dose (74 Gy) and high escalated dose (> or =78 Gy). The optimal duration and timing of hormonal therapy are not well defined. More randomized-controlled trials and meta-analyses are therefore needed to clearly determine the independent role of dose-escalation in high-risk patients treated with hormonal therapy and the optimal duration and timing of hormonal therapy.

Hypofractionated radiotherapy denoted as the "Christie scheme": an effective means of palliating patients with head and neck cancers not suitable for curative treatment.

OBJECTIVES: A prospective study of the efficacy and toxicity profile of patients with squamous cell carcinoma of the head and neck (HNSCC) without curative treatment options treated consistently with hypofractionated radiotherapy schedule. PATIENTS AND METHODS: Between 1995 and 2006, 158 patients with HNSCC, unsuitable for curative treatment, were treated with a hypofractionated scheme of radiotherapy consisting of 16 fractions of 3.125 Gy. Endpoints of the study were response rates, loco-regional control, disease-free survival, overall survival, acute and late toxicity, and quality of life (QoL). RESULTS: Seventy four percent of patients were male, 31% had oropharyngeal cancer and 81% stage IV disease. With 45% complete response and 28% partial response an overall response rate of 73% was achieved, 6% had stable disease, and 21% progressed during or directly after completion of treatment. Median survival time was 17 months and 62 patients (40%) survived > or =1 year after RT. The actuarial rates of loco-regional control, disease-free survival and overall survival were 62%, 32% and 40% at 1-year, respectively and 32%, 14% and 17% at 3-years, respectively. Acute grade > or =3 skin and mucosal toxicities were observed in 45% and 65% of patients, respectively. Severe late toxicity was reported in 4.5% of patients. Of patients surviving > or =1 year after RT, retrospective chart review showed that 50% gained weight, pain improved in 77%, performance status in 47% and only 29% of them was still feeding-tube dependent. CONCLUSIONS: Our hypofractionated radiotherapy scheme is an effective, well-tolerated and safe palliative schedule in HNSCC who are unsuitable for curative treatment options. Using 3.125 Gy per fraction (Christie scheme), excellent palliation was achieved resulting in acceptable response rates, excellent symptom control, acceptable toxicity profile, and good QoL of patients surviving > or =1 year after completion of treatment.