PurposeTo analyze whether local tumor control in advanced nasopharyngeal cancer (NPC) can be optimized by boosting the primary dose by endocavitary brachytherapy (EBT).Methods and MaterialsTo study the role of EBT, three data sets on NPC, that is, the “Vienna”, “Rotterdam,” and “Amsterdam” series, with a total number of 411 advanced NPC patients, were available. The Rotterdam series consisted of 72 patients (34 T1,2N+ and 38 T3,4N0,+) and were treated with neoadjuvant chemotherapy followed by external beam radiotherapy (dose 70/2 Gy). After 70/2 Gy, a boost was applied by EBT (in case of T1,2N+) or stereotactic radiation (in case of T3,4 tumors). The Amsterdam (Antoni van Leeuwenhoek Hospital/The Netherlands Cancer Institute) series consisted of 76 patients (40 T1,2N+ and 36 T3,4N0,+) and were irradiated to a dose of 70/2 Gy with concomitant chemotherapy. No second boost by EBT was applied.ResultsIn the case of T1,2N+ tumors, the local relapse rate (LRR) was significantly smaller if a boost was applied, that is, 0% (0/34, EBT boost) vs. 14% (14/102, no EBT boost) (p=0.023). For the T3,4 tumors, an LRR of 10% (4/38, EBT or stereotactic radiation boost) vs. 15% (17/111, no boost) was found (p=0.463).ConclusionsIn the case of advanced NPC (T1,2N+ vs. T3,4N+,0), for early T-stages (T1,2N+), an EBT boost seems an excellent way to deliver highly conformal high doses of radiation to the nasopharynx, with high local control rates. For advanced T-stages (T3,4N+,0), the reduction in LRR (10% vs. 15%) was not significant (p=0.463).

In organ preservation therapy, for cancer in the head and neck, over the years a number of investigators have noted a signifi cant increase in dysphagia, defi ned as swallowing problems that most likely relate to more aggressive treatment regimes used in order to obtain better tumor control rates. The aggressive nature of the treatment modalities is exemplifi ed by high doses of radiation and/or (accelerated) fractionation regimens, with or without (concomitant) chemotherapy (Levendag et al. 2004). Xerostomia has been well documented in patients treated with chemotherapy (CHT) and/or radiation. It has been argued that the degree of xerostomia corresponds with the amount of dysphagia experienced by the patient (Logemann et al. 2001, 2003). To defi ne potential rehabilitation strategies, it is important to investigate fi rst the anatomical structures and functionality of the swallowing apparatus. Examples of preventative measures are the pre- and posttreatment exercises and/or the introduction of Therabite (Burkhead et al. 2006; Kulbersh et al. 2006). Few studies have examined the association of dysphagia with the location of the primary tumor site (Pauloski et al. 2000, 2002). This chapter analyses the response to validated QOL questionnaires in search of (severe) late side effects, such as swallowing disorders and xerostomia, in patients with oropharyngeal cancers treated between 1991 and 2005 in a single institution (Erasmus MC). The patient retrieval for the current analysis consisted of patients with tonsillar fossa and/or soft palate (TF and/or SP) or base-of-tongue (BOT) tumors treated by radiation therapy (RT). Over time the primary tumor was boosted by various RT techniques, that is, by either a parallel-opposed (P-O) fi eld confi guration, or by 3D conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT), or brachytherapy (BT). A treatment regime using conventional 2 Gy/day fractionation, combined with a BT boost, has been applied in our institute by far the most over a great number of years (1991– 2008) for various reasons: With regard to tumor control, HDR/PDR fractionation is given in an accelerated fashion with intrinsic dose escalation. A high confor-mality is obtained because of an accurate CTV delineation, no PTV margin (because catheters move with movement of target area), and rapid dose fall-off. The invasiveness of the procedure, the need for albeit some dexterity, the logistics in the OR, and patients being medically unfi t for any type of surgical procedure are some of the disadvantages of BT. This chapter reports in particular those patients treated with BT.

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 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 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 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 1 year after completion of treatment.

Purpose: Comparison of quality of life (QoL) and side effects in a randomized trial for early hyperbaric oxygen therapy (HBOT) after radiotherapy (RT).Methods and Materials: From 2006, 19 patients with tumor originating from the tonsillar fossa and/or soft palate (15), base of tongue (1), and nasopharynx (3) were randomized to receive HBOT or not. HBOT consisted of 30 sessions at 2.5 ATA (15 msw) with oxygen breathing for 90 min daily, 5 days per week, applied shortly after the RT treatment was completed. As of 2005, all patients received validated questionnaires (i.e., the European Organization for Research and Treatment of Cancer [EORTC] QLQ-C30, EORTC QLQ Head and Neck Cancer Module (H&N35), Performance Status Scale): before treatment; at the start of RT treatment; after 46 Gy; at the end of RT treatment; and 2, 4, and 6 weeks and 3, 6, 12, and 18 months after follow-up.Results: On all QoL items, better scores were obtained in patients treated with hyperbaric oxygen. The difference between HBOT vs. non-HBOT was significant for all parameters: EORTC H&N35 Swallowing (p = 0.011), EORTC H&N35 Dry Mouth (p = 0.009), EORTC H&N35 Sticky Saliva (p = 0.01), PSS Eating in Public (p 0.027), and Pain in Mouth (visual analogue scale; p < 0.0001).Conclusions: Patients randomized for receiving hyperbaric oxygen after the RT had better QoL scores for swallowing, sticky saliva, xerostomia, and pain in mouth. (C) 2009 Elsevier Inc.

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.

Purpose: To assess the relationship for oropharyngeal (OP) cancer and nasopharyngeal (NP) cancer between the dose received by the swallowing structures and the dysphagia related quality of life (QoL).Methods and Materials: Between 2000 and 2005, 85 OP and 47 NP cancer patients were treated by radiation therapy. After 46 Gy, OP cancer is boosted by intensity-modulated radiation therapy (IMRT), brachytherapy (BT), or frameless stereotactic radiation/cyberknife (CBK). After 46 Gy, the NP cancer was boosted with parallel-opposed fields or IMRT to a total dose of 70 Gy; subsequently, a second boost was given by either BT (11 Gy) or stereotactic radiation (SRT)/CBK (11.2 Gy). Sixty OP and 21 NP cancer patients responded to functional and QoL questionnaires (i.e., the Performance Status Scales, European Organization for Research and Treatment of Cancer H&N35, and M.D. Anderson Dysphagia Inventory). The swallowing muscles were delineated and the mean dose calculated using the original three-dimensional computed tomography-based treatment plans. Univariate analyses were performed using logistic regression analysis.Results: Most dysphagia problems were observed in the base of tongue tumors. For OP cancer, boosting with IMRT resulted in more dysphagia as opposed to BT or SRT/CBK. For NPC patients, in contrast to the first booster dose (46-70 Gy), no additional increase of dysphagia by the second boost was observed.Conclusions: The lowest mean doses of radiation to the swallowing muscles were achieved when using BT as opposed to SRT/CBK or IMRT. For the 81 patients alive with no evidence of disease for at least I year, a dose-effect relationship was observed between the dose in the superior constrictor muscle and the "normalcy of diet" (Performance Status Scales) or "swallowing scale" (H&N35) scores (p < 0.01). (C) 2008 Elsevier Inc.

Background. Our aim was to assess the correlation between the radiation therapy (RT) dose to the mastication apparatus and trismus of oropharyngeal cancer patients.Methods. Eighty-one patients treated with RT were analyzed. The masseter, pterygoid, and temporalis muscles and the coronoid and condyl were delineated on axial CT slices. The mean dose in these structures was correlated with outcome of quality of life questionnaires.Results. Fifty-six (88%) patients responded; 16% of the patients scored grade 3/4 on the Head & Neck 35 "opening mouth" question. A significant correlation was observed between dose in masseter and pterygoid muscles and trismus (p =.02).Conclusion. Patients treated with brachytherapy received a lower dose in masticatory muscles. A steep dose-effect relationship between mean dose in masseter muscle and pterygoid muscles and the probability of having trismus complaints was observed; with every additional 10 Gy to the pterygoid muscle, an increase of the probability of trismus of 24% was observed. (c) 2008 Wiley Periodicals, Inc.

PURPOSE: Based on earlier Studies we were interested in finding Out if longitudinal assessment of quality of life (QoL) and costs in long-term Survivors of oropharyngeal cancers treated with external beam radiation therapy and brachytherapy (BT) or surgery and postoperative radiotherapy showed a change in QoL over the years. Besides, we were curious to know how much the costs per life year and the QALY would be for this patientMETHODS AND MATERIALS: Performance status scales: eating in public, understandability of speech, normalcy of diet, xerostomia and ability to swallow were determined in 2003 and 2005. In 2005, the responses to EORTC QLQ-C30, EORTC H&N35, and the Euroqol questionnaire were also measured. Costs and quality-adjusted life years (QALYs) were calculated.RESULTS: Eating in public, understandability of speech, and normalcy of diet significantly differed in favor of BT. Surgical patients experienced more speech, teeth, and mouth-opening problems. Mean costs and QALYs for BT were (sic)16,112 and (sic)56,060 and for surgery (sic)26,590 and (sic)93,275, respectively.CONCLUSIONS: QoL scores don't change over little. Due to the number of admission days, surgery is more costly. Difference in costs for QALYs in favor of BT was observed. (C) 2008 Published by Elsevier Inc on behalf of American Brachytherapy Society.

Purpose: Dysphagia is a major late complication of intensive chemoradiotherapy of head and neck cancer. The initial clinical results of intensity-modulated radiotherapy (IMRT), or brachytherapy, planned specifically to reduce dysphagia are presented.Patients and Methods: Previous research at Michigan University has suggested that the pharyngeal constrictors and glottic and supraglottic larynx are likely structures whose damage by chemo-RT causes dysphagia and aspiration. In a prospective Michigan trial, 36 patients with oropharyngeal (n = 31) or nasopharyngeal (n = 5) cancer underwent chemo-IMRT. IMRT cost functions included sparing noninvolved pharyngeal constrictors and the glottic and supraglottic larynx. After a review of published studies, the retropharyngeal nodes at risk were defined as the lateral, but not the medial, retropharyngeal nodes, which facilitated sparing of the swallowing structures. In Rotterdam, 77 patients with oropharyngeal cancer were treated with IMRT, three dimensional RT, or conventional RT; also one-half received brachytherapy. The dysphagia endpoints included videofluoroscopy and observer-assessed scores at Michigan and patient- reported quality-of-life instruments in both studies.Results: In both studies, the doses to the upper and middle constrictors correlated highly with the dysphagia endpoints. In addition, doses to the glottic and supraglottic larynx were significant in the Michigan series. In the Rotterdam series, brachytherapy (which reduced the doses to the swallowing structures) was the only significant factor on multivariate analysis.Conclusion: The dose-response relationships for the swallowing structures found in these studies suggest that reducing their doses, using either IMRT aimed at their sparing, or brachytherapy, might achieve clinical gains in dysphagia. (C) 2007 Elsevier Inc.

As a basis for making decisions regarding optimal treatment for patients with tonsillar fossa and soft palate tumors, we conducted a preliminary investigation of costs and quality of life (QoL) for two modalities [brachytherapy (BT) and robotic radiosurgery] used to boost radiation to the primary tumors following external beam radiotherapy. BT was well established in our center; a boost by robotic radiosurgery was begun more recently in patients for whom BT was not technically feasible. Robotic radiosurgery boost treatment has the advantage of being non-invasive and is able to reach tumors in cases where there is deep parapharyngeal tumor extension. A neck dissection was performed for patients with nodal-positive disease. Quality of life (pain and difficulty swallowing) was established in long-term follow-up for patients undergoing BT and over a one-year follow-up in robotic radiosurgery patients. Total hospital costs for both groups were computed. Our results show that efficacy and quality of life at one year are comparable for BT and robotic radiosurgery. Total cost for robotic radiosurgery was found to be less than BT primarily due to the elimination of hospital admission and operating room expenses. Confirmation of robotic radiosurgery treatment efficacy and reduced morbidity in the long term requires further study. Quality of life and cost analyses are critical to Health Technology Assessments (HTA). The present study shows how a preliminary HTA of a new medical technology such as robotic radiosurgery with its typical hypofractionation characteristics might be based on short-term clinical outcomes and assumptions of equivalence.

Introduction: This article reports on the effectiveness, cosmetic outcome, and costs of interstitial high-dose-rate (HDR) brachytherapy for early-stage cancer of the nasal vestibule (NV) proper and/or columella high-dose-rate (HDR).Methods and Materials: Tumor control, survival, cosmetic outcome, functional results, and costs were established in 64 T1/T2N0 nasal vestibule cancers treated from 1991-2005 by fractionated interstitial radiation therapy (IRT) only. Total dose is 44 Gy: 2 fractions of 3 Gy per day, 6-hour interval, first and last fraction 4 Gy. Cosmesis is noted in the chart by the medical doctor during follow-up, by the patient (visual analog scale), and by a panel. Finally, full hospital costs are computed.Results: A local relapse-free survival rate of 92% at 5 years was obtained. Four local failures were observed; all four patients were salvaged. The neck was not treated electively; no neck recurrence in follow-up was seen. Excellent cosmetic and functional results were observed. With 10 days admission for full treatment, hospital costs amounted to EUR5772 ($7044).Conclusion: Excellent tumor control, cosmesis, and function of nasal airway passage can be achieved when HDR-IRT for T1/T2N0 NV cancers is used. For the more advanced cancers (Wang classification: T3 tumor stage), we elect to treat by local excision followed by a reconstructive procedure. The costs, admission to hospital inclusive, for treatment by HDR-IRT amounts to EUR5772 ($7044 US). This contrasts substantially with the full hospital costs when NV cancers are treated by plastic reconstructive surgery, being on average threefold as expensive. (c) 2006 Elsevier Inc.