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.

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.

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.

Quality of life of oropharyngeal cancer patients treated with brachytherapy.

Brachytherapy (BT) is a highly conformal (accurate clinical target volume delineation, no planning target volume margin) radiotherapy technique; the radioactive source, guided by afterloading catheters, is implanted into the heart of the tumor. The localized high dose of radiation enables high tumor control rates and, because of rapid dose fall-off, sparing of the adjacent normal tissues. At the Erasmus Medical Center, excellent results were observed: 5-year local regional control of 84%, 5-year disease-free survival of 59%, and 5-year overall survival of 64%. Therefore, in the case of moderately sized tumors, for well-trained, skillful physicians, BT is the therapy of choice (if technically feasible). However, side effects are not totally negligible, partly because of the cumulative dose of BT and the first series of 46/2 Gy. However, patients treated with BT still have a better swallowing-related quality of life, which might improve further if summation of BT and the first series of 46/2 Gy, as well as autocontouring of the neck levels, are realized. So far, there is no significant relationship between the -quality index of the BT implants and local control/overall survival and/or quality of life.

Results of fiberoptic endoscopic evaluation of swallowing vs. radiation dose in the swallowing muscles after radiotherapy of cancer in the oropharynx.

BACKGROUND AND PURPOSE: Dysphagia is a serious complaint but frequently underreported. This paper assesses for oropharyngeal cancer (OPC) the relationship between the dose received by the swallowing structures, and the findings of a fiberoptic endoscopic evaluation of the swallowing process (FEES). MATERIALS AND METHODS: Between 2000 and 2005, 60 of 67 OPC patients local-regionally NED for at least one year following treatment responded to three types of QoL questionnaires; i.e. Performance Status Scales, EORTC H&N35, and M.D. Anderson Dysphagia Inventory. Twenty-four patients agreed to the FEES procedure. The main swallowing muscles were delineated, with the mean dose per muscle calculated using the original 3D CT-based treatment plans. Regression analysis was performed between FEES variables and the doses in the different swallowing muscles and the dysphagia related questionnaires. RESULTS: A significant relationship was found between the results of FEES and the mean dose in the superior constrictor muscle (SCM). Some of the subjective dysphagia complaints were significantly correlated with the FEES variables in this retrospectively study. CONCLUSION: A higher dose in the SCM generally results in worsening of the findings obtained by the FEES examination.

Bladder function preservation with brachytherapy, external beam radiation therapy, and limited surgery in bladder cancer patients: Long-term results [corrected].

PURPOSE: To report long-term results of a bladder preservation strategy for muscle-invasive bladder cancer (MIBC) using external beam radiation therapy and brachytherapy/interstitial radiation therapy (IRT). METHODS AND MATERIALS: Between May 1989 and October 2011, 192 selected patients with MIBC were treated with a combined regimen of preoperative external beam radiation therapy and subsequent surgical exploration with or without partial cystectomy and insertion of source carrier tubes for afterloading IRT using low dose rate and pulsed dose rate. Data for oncologic and functional outcomes were prospectively collected. The primary endpoints were local recurrence-free survival (LRFS), bladder function preservation survival, and salvage cystectomy-free survival. The endpoints were constructed according to the Kaplan-Meier method. RESULTS: The mean follow-up period was 105.5 months. The LRFS rate was 80% and 73% at 5 and 10 years, respectively. Salvage cystectomy-free survival at 5 and 10 years was 93% and 85%. The 5- and 10-year overall survival rates were 65% and 46%, whereas cancer-specific survival at 5 and 10 years was 75% and 67%. The distant metastases-free survival rate was 76% and 69% at 5 and 10 years. Multivariate analysis revealed no independent predictors of LRFS. Radiation Therapy Oncology Group grade ≥3 late bladder and rectum toxicity were recorded in 11 patients (5.7%) and 2 patients (1%), respectively. CONCLUSIONS: A multimodality bladder-sparing regimen using IRT offers excellent long-term oncologic outcome in selected patients with MIBC. The late toxicity rate is low, and the majority of patients preserve their functional bladder.

Unilateral neck irradiation for well-lateralized oropharyngeal cancer.

BACKGROUND AND PURPOSE: To investigate the impact of unilateral neck irradiation (UNI) of well-lateralized oropharyngeal cancer (OPC) on outcome and toxicity. MATERIALS AND METHODS: Unilateral neck IMRT was applied to 185 consecutive patients with well-lateralized OPC (restricted to tonsillar fossa, soft palate with at least 1cm from midline or lateral pharyngeal wall). Endpoints were regional control (RC), local control (LC), disease-free survival (DFS), overall survival (OS), and toxicity. RESULTS: Six regional failures were reported (3.2%); 2 were contralateral (1.1%). The 5-year Kaplan-Meier estimates of RC, LC, DFS, and OS were 96%, 91%, 84%, and 70%, respectively. Feeding tube was given to 11.3%. Chemotherapy was significantly predictive for toxicity. However, no patient was still feeding tube dependent 6 weeks after treatment. Overall grade 3 late toxicity was 2.2%. Grade 3 xerostomia was reported in only 1 patient while no patient developed grade 3 dysphagia. CONCLUSION: This largest study on unilateral neck IMRT for well-lateralized OPC showed excellent outcome and favorable toxicity profile. Given the increasing incidence of OPC, especially among younger patients, and the favorable results reported in the current study and by other investigators, expanding the indications for UNI still needs to be further investigated in prospective, preferably, randomized trials.

Stereotactic body radiotherapy with a focal boost to the MRI-visible tumor as monotherapy for low- and intermediate-risk prostate cancer: early results.

BACKGROUND: There is growing evidence that prostate cancer (PC) cells are more sensitive to high fraction dose in hypofractionation schemes. High-dose-rate (HDR) brachytherapy as monotherapy is established to be a good treatment option for PC using extremely hypofractionated schemes. This hypofractionation can also be achieved with stereotactic body radiotherapy (SBRT). We report results on toxicity, PSA response, and quality of life (QOL) in patients treated with SBRT for favorable-risk PC. METHODS: Over the last 4 years, 50 hormone-naïve patients with low- and intermediate-risk PC were treated with SBRT to a total dose of 38 Gy delivered in four daily fractions of 9.5 Gy. An integrated boost to 11 Gy per fraction was applied to the dominant lesion if visible on MRI. Toxicity and QoL was assessed prospectively using validated questionnaires. RESULTS: Median follow-up was 23 months. The 2-year actuarial biochemical control rate was 100%. Median PSA nadir was 0.6 ng/ml. Median International Prostate Symptoms Score (IPSS) was 9/35 before treatment, with a median increase of 4 at 3 months and remaining stable at 13/35 thereafter. The EORTC/RTOG toxicity scales showed grade 2 and 3 gastrointestinal (GI) acute toxicity in 12% and 2%, respectively. The late grade 2 GI toxicity was 3% during 24 months FU. Genitourinary (GU) grade 2, 3 toxicity was seen in 15%, 8%, in the acute phase and 10%, 6% at 24 months, respectively. The urinary, bowel and sexual domains of the EORTC-PR25 scales recovered over time, showing no significant changes at 24 months post-treatment. CONCLUSIONS: SBRT to 38 Gy in 4 daily fractions for low- and intermediate-risk PC patients is feasible with low acute and late genitourinary and gastrointestinal toxicity. Longer follow-up preferably within randomized studies, is required to compare these results with standard fractionation schemes.

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.

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.

Intensity-modulated radiotherapy followed by a brachytherapy boost for oropharyngeal cancer.

BACKGROUND: The purpose of this study was to reduce the incidence of radiation-induced toxicity in patients with early-stage oropharyngeal cancer, using highly conformal radiation techniques. METHODS: Between 2000 and 2011, 167 patients with T1-3N0-3 oropharyngeal cancer were treated with 46-Gy intensity-modulated radiation therapy (IMRT) followed by 22-Gy brachytherapy boost. In patients with node-positive disease, neck dissection was performed. RESULTS: The 5-year Kaplan-Meier estimates of local control, regional control, disease-free survival (DFS), and overall survival (OS) were 94%, 97%, 84%, and 72%, respectively. Feeding tubes were required in 26% of the patients. Grade ≥2 late xerostomia and dysphagia were 11% and 8%, respectively. Chemotherapy, tumor subsite, and bilateral neck irradiation correlate significantly with toxicity. Quality of life (QOL) scores deteriorate during and shortly after treatment but returned in all scales to baseline scores within 6 to 12 months, with the exception of xerostomia. CONCLUSION: Brachytherapy boost and neck dissection (in node-positive oropharyngeal cancer) after 46-Gy of IMRT resulted in excellent outcomes with low incidence of late toxicity and good QOL scores.

Node-positive hypopharyngeal cancer treated by (chemo)radiotherapy: impact of up-front neck dissection on outcome, toxicity, and quality of life.

BACKGROUND: To investigate the impact of up-front neck dissection on the outcome of patients with node-positive hypopharyngeal cancer (HPC) treated with (chemo)radiation. METHODS: Of 135 consecutive patients with node-positive HPC, 32 patients underwent up-front neck dissection followed by (chemo)radiation (group 1), and 103 patients received definitive (chemo)radiation (group 2). RESULTS: The 3-year regional, local and distant control for groups 1 and 2 were 92% versus 87% (p = .37), 84% versus 72% (p = .15), and 80% versus 62% (p = .08), respectively. High T classification was the only significant predictor for poor overall survival on multivariate analysis (OR = 3.0, p = .02). Acute and late toxicities and the prospectively assessed quality of life were comparable in both groups. CONCLUSION: Upfront neck dissection followed by (chemo)radiation did not negatively impact on oncologic outcomes, toxicity, or quality of life and therefore is to be regarded as a safe and effective treatment option for small HPC with bulky nodal disease, especially in busy radiation departments with unacceptably long waiting time for definitive (chemo)radiation.

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.

The impact of treatment modality and radiation technique on outcomes and toxicity of patients with locally advanced oropharyngeal cancer.

OBJECTIVES/HYPOTHESIS: To investigate the impact of treatment modality and radiation technique on oncologic outcomes and toxicity of patients with locally advanced oropharyngeal cancer (OPC). STUDY DESIGN: Retrospective analysis of outcomes and toxicity. METHODS: Between 2000 and 2011, 204 consecutive patients with locally advanced OPC were treated with definitive (chemo)radiotherapy using 3-dimensional conformal (3DCRT) or intensity-modulated radiotherapy (IMRT). Endpoints were local control (LC), regional control (RC), disease-free survival (DFS), cause-specific survival (CSS), and overall survival (OS), and toxicity. RESULTS: After a median follow-up of 44 months (range 4-134), the 5-year Kaplan-Meier estimates of LC, RC, DFS, CSS, and OS were 78%, 92%, 60%, 64%, and 48%, respectively. Grade 3 mucositis and dysphagia (feeding-tube dependency) were reported in 75% and 65%, respectively. The overall incidence of grade ≥ 2 and grade 3 late toxicities were 44% and 16%, respectively. Dysphagia and xerostomia were the most frequently reported late toxicity. Chemotherapy was significantly predictive for improved outcomes and increased toxicity. IMRT was significantly correlated with reduced toxicity. CONCLUSIONS: Compared to radiation alone, chemoradiotherapy significantly improved oncologic outcomes, but with significantly increased toxicity. Compared to 3DCRT, the introduction of IMRT resulted in a significant reduction of acute and late toxicity with slightly better, or at least comparable, outcomes. Despite the improvements achieved by the implementation of chemo-IMRT, different new strategies to further improve outcome and reduce toxicity need to be thoroughly investigated in prospective, preferably, randomized trials.

Prevalence of left and balanced coronary arterial dominance decreases with increasing age of patients at autopsy. A postmortem coronary angiograms study.

BACKGROUND: In patients presenting with an acute coronary syndrome, left over right coronary dominance appears to be independently associated with increased long-term mortality. This could lead to decreasing numbers of patients with a left dominant coronary artery system in older age groups. METHODS: We assessed the type of coronary dominance in different age groups in postmortem angiograms that were routinely performed at autopsy between 1993 and 2007. Coronary dominance was determined by identifying the origin of the posterior descending artery and posterolateral branches on postmortem angiography. Age, gender, and cause of death were recorded from the autopsy database. The prevalence of left dominant, right dominant, and codominant systems was determined in three increasing age categories, with cutoffs based on tertiles. RESULTS: A total 1620 coronary angiograms were assessed; 167 were excluded because it was not possible to determine coronary dominance. The median age of all patients was 71 years; 56% were male. Of all deaths, 40% were classified as cardiac. Regarding coronary dominance, 81.2% was right, 9.1% was left, and 9.7% was codominant. Overall, a decrease in prevalence of left and codominant coronary systems was observed with increasing age in the three age cohorts (≤ 63 years, 64-75 years, and ≥ 76 years) (P=.001 for overall comparison). CONCLUSIONS: In this large autopsy cohort, the prevalence of a left dominant or codominant coronary system decreased with increasing age. These findings could relate to a slightly higher risk of mortality in case of left versus right coronary artery occlusion.

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.

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.

Long-term outcomes and quality of life of 186 patients with primary parotid carcinoma treated with surgery and radiotherapy at the Daniel den Hoed Cancer Center.

PURPOSE: To assess the outcomes, toxicity, and quality of life (QOL) of patients with primary parotid carcinoma treated with surgery and postoperative radiotherapy at the Daniel den Hoed Cancer Center. METHODS AND MATERIALS: Between 1995 and 2010, 186 patients with parotid carcinoma were treated with parotidectomy with or without neck dissection, followed by radiotherapy. Elective nodal irradiation (ENI) was applied to high-risk, node-negative disease. End points were locoregional control (LRC), disease-free survival (DFS), cause-specific survival (CSS), and overall survival (OS), late toxicity, and QOL. RESULTS: After a median follow-up of 58 months (range, 4-172 months), the 5-year Kaplan-Meier estimates for LRC, DFS, CSS, and OS were 89%, 83%, 80%, and 68%, respectively. Forty-five events were reported: 24 distant metastases (DM) and 21 locoregional failures (LRF). Event-free survival rates by histological types were 89%, 78%, 76%, 74%, and 70% for acinic cell, mucoepidermoid, adenoid cystic, adenocarcinoma, and squamous cell carcinoma, respectively. More LRF were reported in patients with squamous cell and high-grade mucoepidermoid carcinoma (21% and 19%, respectively) than in patients with other histological types (p = 0.04) and more DM in patients with adenoid cystic and adenocarcinoma (20% and 19%, respectively) than in patients with other types (p = 0.03). None of the high-risk node-negative patients who received ENI developed regional failure. On multivariate analysis, T stage, N stage, grade, and presence of perineural invasion and facial paralysis correlated significantly with DFS. The 5-year cumulative incidence of grade ≥2 late toxicity was 8%. QOL scores deteriorate during and shortly after treatment but returned in almost all scales to baseline scores within 6 months. CONCLUSIONS: Of the entire group, surgery and postoperative radiotherapy resulted in excellent outcomes with minimal side effects and preservation of good QOL scores. However, in view of the pattern of failures observed in this study, the role of adjuvant systemic or targeted therapy in patients at high risk of DM should be investigated in prospective trials.

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.