Local control in advanced cancer of the nasopharynx: is a boost dose by endocavitary brachytherapy of prognostic significance?

PURPOSE: To analyze whether local tumor control in advanced nasopharyngeal cancer (NPC) can be optimized by boosting the primary dose by endocavitary brachytherapy (EBT). METHODS AND MATERIALS: To 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 70/2Gy). After 70/2Gy, 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 70/2Gy with concomitant chemotherapy. No second boost by EBT was applied. RESULTS: In 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). CONCLUSIONS: In 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).

Early hyperbaric oxygen therapy for reducing radiotherapy side effects: early results of a randomized trial in oropharyngeal and nasopharyngeal cancer.

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.

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.

Longitudinal changes in quality of life and costs in long-term survivors of tumors of the oropharynx treated with brachytherapy or surgery.

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 patient group. METHODS 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 16,112 euros and 56,060 euros and for surgery 26,590 euros and 93,275 euros, respectively. CONCLUSIONS: QoL scores don't change over time. Due to the number of admission days, surgery is more costly. Difference in costs for QALYs in favor of BT was observed.

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.

Treatment techniques and site considerations regarding dysphagia-related quality of life in cancer of the oropharynx and nasopharynx.

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 1 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).

Trismus in patients with oropharyngeal cancer: relationship with dose in structures of mastication apparatus.

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.

Can IMRT or brachytherapy reduce dysphagia associated with chemoradiotherapy of head and neck cancer? The Michigan and Rotterdam experiences.

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.

Dysphagia disorders in patients with cancer of the oropharynx are significantly affected by the radiation therapy dose to the superior and middle constrictor muscle: a dose-effect relationship.

PURPOSE/OBJECTIVE: To assess the relationship between the radiation therapy (RT) dose received by the muscular components of the swallowing (sw) apparatus and - dysphagia related - quality of life (QoL) in oropharyngeal cancer. MATERIALS/METHODS: Between 2000 and 2005, 81 patients with SCC of the oropharynx were treated by 3DCRT or IMRT, with or without concomitant chemotherapy (CHT); 43 out of these 81 patients were boosted by brachytherapy (BT). Charts of 81 patients were reviewed with regard to late dysphagia complaints; 23% experienced severe dysphagia. Seventeen patients expired. Fifty-six out of 64 (88%) responded to quality of life (QoL) questionnaires; that is, the Performance Status Scales of List, EORTC H&N35, and the M.D. Anderson Dysphagia Inventory. The superior (scm), middle (mcm), and inferior constrictor muscle (icm), the cricopharyngeus muscle and the inlet of the esophagus, are considered of paramount importance for swallowing. The mean dose was calculated in the muscular structures. Univariate analysis and multivariate analysis were performed using the proportional odds model. RESULTS: Mean follow-up was 18 months (range 2-34) for IMRT, and 46 months for 3DCRT (range 2-72). At 3-years, a LRC of 84%, DFS of 78% and OS of 77% were observed. A significant correlation was observed between the mean dose in the scm and mcm, and severe dysphagia complaints (univariate analysis). A steep dose-effect relationship, with an increase of the probability of dysphagia of 19% with every additional 10 Gy, was established. In the multivariate analysis, BT (dose) was the only significant factor. CONCLUSION: A dose-effect relationship between dose and swallowing complaints was observed. One way to improve the QoL is to constrain the dose to be received by the swallowing muscles.

Interstitial radiation therapy for early-stage nasal vestibule cancer: a continuing quest for optimal tumor control and cosmesis.

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 euro5772 (7044 US dollars). 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 euro5772 (7044 US dollars). This contrasts substantially with the full hospital costs when NV cancers are treated by plastic reconstructive surgery, being on average threefold as expensive.

Cancer in the oropharynx: cost calculation of different treatment modalities for controlled primaries, relapses and grade III/IV complications.

BACKGROUND AND PURPOSE: This paper presents a model for cost calculation using the different treatment modalities for oropharyngeal (OPh) cancers used in our hospital. We compared full hospital costs, the associated costs of localregional relapses (LRR) and/or treatment related grade III/IV complications. MATERIALS AND METHODS: Patients with OPh cancer are treated in the Erasmus MC preferably by an organ function preservation protocol. That is, by external beam radiation therapy (EBRT) followed by a brachytherapy (BT) boost, and neck dissection in case of N+ disease (BT-group: 157 patients). If BT is not feasible, resection with postoperative EBRT (S-group [S=Surgery]: 110 patients) or EBRT-alone (EBRT-group: 77 patients) is being pursued. Actuarial localregional control (LRC), disease free survival (DFS) and overall survival (OS) at 5-years were calculated according to the Kaplan-Meier method. The mean costs per treatment group for diagnosis, primary Tx per se, follow-up, (salvage of) locoregional relapse (LRR), distant metastasis (DM), and/or grade III/IV complications needing clinical admission, were computed. RESULTS: For the BT-, S-, or EBRT treatment groups, LRC rates at 5-years were 85, 82, and 55%, for the DFS, 61, 48, and 43%, and for the OS 65, 52, and 40%, respectively. The mean costs of primary Tx in case of the BT-group is 13,466; for the S-group 24,219, and 12,502 for the EBRT-group. The mean costs of S (the main salvage modality) for a LRR of the BT group or EBRT-group, were 17,861 and 15,887, respectively. The mean costs of clinical management of Grade III/IV complications were 7184 (BT-group), 16,675 (S-group) and 6437 (EBRT-group). CONCLUSION: The clinical outcome illustrates excellent LRC rates at 5-years for BT (85%), as well as for S (82%). The relatively low 55% LRC rate at 5-years for EBRT probably reflects a negative selection of patients. It is of interest that the total mean costs of patients alive with no evidence of disease is least for the BT-group: 15,101 as opposed to 25,288 (S) and 18,674 (EBRT). Main underlying cause for the high costs with S as opposed to RT alone is the number of associated clinical admission days, not only during primary treatment, but also at relapse. This might be taken into consideration when treating these patients.

Brachytherapy versus surgery in carcinoma of tonsillar fossa and/or soft palate: late adverse sequelae and performance status: can we be more selective and obtain better tissue sparing?

PURPOSE: To report on the tumor control, adverse late normal tissue sequelae, and functional performance in patients with tonsillar fossa and/or soft palate (SP) tumors. The aim of the study is to validate the use of a more selective clinical target volume in conjunction with highly conformal radiotherapy (RT) techniques to better spare the surrounding normal tissues. METHODS AND MATERIALS: Between 1986 and 2001, T1-T3 tonsillar fossa/SP tumors were treated in the Erasmus Medical Center using external beam radiotherapy (EBRT) to 46 Gy in 2-Gy fractions to the primary tumor and neck, followed by brachytherapy (BT) to the primary. Neck dissection was performed for node-positive disease (BT group; 104 patients). If BT was not feasible, patients underwent surgery and postoperative RT (PORT) to a dose of 50-70 Gy in 2-Gy fractions (surgery group; 86 patients). Local control, regional control, disease-free survival, and overall survival were determined. Late side effects were scored using the Radiation Therapy Oncology Group criteria. Univariate and multivariate Cox regression analyses were performed for regional failure (RF), with the parameters gender, age, site, TN stage, modality, dose, and overall treatment time. Recurrences in the contralateral neck were also related to significant ipsilateral involvement of the base of tongue and/or involvement of the SP crossing the midline. To determine the performance status scale scores and degree of xerostomia, a survey was conducted among patients living with no evidence of disease and a minimum of 2 years of follow-up. For that purpose, a research nurse interviewed patients regarding eating in public, normalcy of diet, normalcy of speech, and xerostomia. RESULTS: The tumor control rates after BT vs. surgery at 5 years were 88% vs. 88% for local control; 93% vs. 85% for regional control; 57% vs. 52% for disease-free survival; 67% vs. 57% for overall survival; and 5% vs. 6% for RF. No patient had RF in the contralateral untreated N0 neck (0 of 14 vs. 0 of 15). Multivariate Cox regression analysis for RF was statistically significant for Stage T2 vs. T3 (hazard ratio 0.09) and for the dose to the neck >46 Gy (hazard ratio, 8.7; 95% confidence interval, 1.3-57.1). The significant late side effects in the BT group vs. surgery group were ulcer in 39% vs. 7% (p = 0.001) and trismus in 1% vs. 21% (p = 0.005). The performance status scale scores and response to questions regarding xerostomia for BT vs. surgery revealed no statistically significant differences for eating in public, normalcy of diet, normalcy of speech, and xerostomia. The mean visual analog score for xerostomia was 5.5 in the BT group vs. 6 in the surgery group. CONCLUSION: Excellent locoregional control was obtained in T1-T3 tonsillar fossa and/or SP tumors. The rate at 10 years was 84% (BT group) vs. 78% (surgery group). However, adverse late side effects were not negligible. In addition to modality-specific side effects (ulcer/trismus), both treatment groups were significantly affected by xerostomia. Only 6 recurrences (4%) were observed in the 149 electively treated contralateral necks, and no relapses were seen in the 29 untreated contralateral necks. We, therefore, suggest that it is not necessary to treat the contralateral neck, unless the tumor extends beyond the midline of the soft palate (uvula) or beyond the lateral one-third of the ipsilateral base of the tongue. Moreover, with the currently available CT-based neck level definitions, more conformal contours (i.e., tighter boundaries) around the clinical target volume can be designed. In this way, critical structures such as the temporomandibular joint and part of the pterygoid muscles can be avoided more easily. Also, when using highly conformal treatment techniques (e.g., intensity-modulated RT), one can further reduce the dose to the major salivary glands and oral mucosa. We believe these measures will lead to less trismus and less xerostomia.

Cost analysis comparing brachytherapy versus surgery for primary carcinoma of the tonsillar fossa and/or soft palate.

PURPOSE: Locoregional control rates, late normal tissue sequelae, and functional outcome scores have not been different for tonsillar fossa and/or soft palate tumors treated by either brachytherapy (BT) or surgery in an organ function preservation protocol. For additional prioritizing in clinical decision-making, we focused on a comparison of the full hospital costs of the different treatment options. METHODS AND MATERIALS: Between 1986 and 2001, tonsillar fossa and/or soft palate tumors were treated by external beam radiotherapy (EBRT) to the primary tumor and neck, followed by fractionated BT to the primary. Neck dissection (ND) was performed for node-positive disease (BT group; 104 patients). If BT was not feasible, resection combined with postoperative EBRT was executed (surgery group; 86 patients). Locoregional control, disease-free survival, and overall survival were calculated according to the Kaplan-Meier method. The performance status scales, late side effects, and degree of xerostomia have been previously reported. This paper focused on the hospital and follow-up costs for the treatment groups EBRT and BT with or without ND compared with surgery followed by postoperative RT (PORT). Finally, these costs were also computed for future treatment strategies (e.g., better sparing of normal tissues by intensity-modulated RT [IMRT]). RESULTS: Locoregional control, disease-free survival, and overall survival rate at 5 years for patients treated with EBRT and BT with or without ND vs. surgery plus PORT was 80% vs. 78%, 58% vs. 55%, and 67% vs. 57%, respectively. The major late side effect was xerostomia. Dry mouth syndrome affected the BT group and surgery group equally. The total costs for all treatment groups were 14,262 euro (BT group), 16,628 euro (BT plus ND group), 18,782 euro (surgery plus PORT group), 14,532 euro (IMRT group), and 16,897 euro (IMRT plus ND group). CONCLUSION: Excellent locoregional tumor control was observed with either modality, with no statistically significant differences in the incidence of the most noted side effect xerostomia. The total costs for BT were less than for surgery: 16,628 euro (19,452 dollars) for EBRT plus BT plus ND vs. 18,782 euro(22,074 dollars) for surgery plus PORT. To reduce the morbidity of xerostomia, we propose further optimizing our organ function preservation protocol by implementing IMRT as a more conformal, tissue-sparing, RT technique. This is of particular interest because the costs of IMRT plus ND (16,897 euro; 19,767 dollars) were not very different from those for BT plus ND (16,628 euro; 19,452 dollars) and were far less than the costs for surgery.

Rotterdam and Brussels CT-based neck nodal delineation compared with the surgical levels as defined by the American Academy of Otolaryngology-Head and Neck Surgery.

PURPOSE/OBJECTIVE: Rotterdam and Brussels have independently published guidelines for the definition and delineation of CT-based neck nodal Levels I-VI. This paper first reports on the adequacy of contouring of the Rotterdam delineation protocol. Rotterdam and Brussels differed slightly in translating the original surgical level definitions as proposed by the 2002 American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) to CT guidelines. To adapt to the surgical level definitions to come to a unifying concept, adjustments of both CT-based classifications are proposed. METHODS AND MATERIALS: The clinical neck nodal target volumes of patients irradiated in Rotterdam by three-dimensional conformal radiotherapy (3D-CRT) between December 1998 and March 2001 were reviewed. Thirty-four patients with N0 and 27 patients with N+ disease with primary tumors located in the oral cavity (n = 1) oropharynx (n = 24), hypopharynx (n = 7), and larynx (n = 29) were evaluated. Seven patients underwent unilateral (3 N0 patients, 4 N+ patients) and 54 underwent bilateral (31 N0 patients, 23 N+ patients) irradiation of the neck. In 11 N+ patients, 3D-CRT of the neck was followed by unilateral neck dissection. The dose to the primary and nonresected N+ necks was 70 Gy and to the N0 neck was 46 Gy. Neck levels were analyzed for adequacy of contouring, dose distribution, and patterns of relapse. The mean dose and the percentage of the volume receiving a minimum of 95% (V95) or >107% (V107) of the prescribed dose was computed. RESULTS: In 4 patients treated with bilateral 3D-CRT, contouring was not in concordance with the guidelines of the protocol. The V95 and V107 in the 81 adequately contoured N0 necks (63 irradiated N0 necks from 33 N0 patients, 18 irradiated N0 necks from 24 N+ patients) was 95.6% and 6.3%, respectively. For the 26 N+ necks (15 N+ necks from 13 N+ RT-only patients, 11 N+ necks from 11 preoperatively irradiated patients), the V95 and V107 was 94.6% and 6.7%, respectively. With a median follow-up of 29 months, in 4 (8.6%) of 46 patients treated by 3D-CRT only, regional relapse was found. An actuarial regional and locoregional relapse-free survival and disease-free survival rate at 3 years of 90%, 78%, and 68%, respectively, was observed. All regional relapses were observed in the N0 necks of patients with supraglottic laryngeal carcinoma. Taking the surgical 2002 AAO-HNS classification as a reference, adjustments are proposed for the Rotterdam and Brussels delineation protocols to arrive at a unified CT-based neck nodal classification. CONCLUSION: Adequate dose coverage for the Rotterdam CT-based contours of the neck nodal levels was found. In the RT-only patients, only four failures were observed: one regional and three locoregional relapses. As a next step in optimizing the current Rotterdam and Brussels CT-based delineation protocols, adaptations are proposed to resolve the discrepancies compared with the 2002 AAO-HNS surgical classification.

High-dose, high-precision treatment options for boosting cancer of the nasopharynx.

PURPOSE: The aim of the study is to define the role and type of high-dose, high-precision radiation therapy for boosting early staged T1,2a, but in particular locally advanced, T2b-4, nasopharyngeal cancer (NPC). MATERIALS AND METHODS: Ninety-one patients with primary stage I-IVB NPC, were treated between 1991 and 2000 with 60-70Gy external beam radiation therapy (ERT) followed by 11-18Gy endocavitary brachytherapy (ECBT) boost. In 1996, for stage III-IVB disease, cisplatinum (CDDP)-based neoadjuvant chemotherapy (CHT) was introduced per protocol. Patients were analyzed for local control and overall survival. For a subset of 18 patients, a magnetic resonance imaging (MRI) scan at 46Gy was obtained. After matching with pre-treatment computed tomogram, patients (response) were graded into four categories; i.e. LD (T1,2a, with limited disease, i.e. disease confined to nasopharynx), LRD (T2b, with limited residual disease), ERD (T2b, with extensive residual disease), or patients initially diagnosed with T3,4 tumors. Dose distributions for ECBT (Plato-BPS v. 13.3, Nucletron) were compared to parallel-opposed three-dimensional conformal radiation therapy (Cadplan, Varian Dosetek v. 3.1), intensity modulated radiation therapy (IMRT) (Helios, Varian) and stereotactic radiotherapy (SRT) (X-plan, Radionics v. 2.02). RESULTS: For stage T1,2N0,1 tumors, at 2 years local control of 96% and overall survival of 80% were observed. For the poorest subset of patients, well/moderate/poorly differentiated T3,4 tumors, local control and overall survival at 2 years with CHT were 67 and 67%, respectively, vs. local control of 20% and overall survival of 12% without CHT. For LD and LRD, conformal target coverage and optimal sparing can be obtained with brachytherapy. For T2b-ERD and T3,4 tumors, these planning goals are better achieved with SRT and/or IMRT. CONCLUSIONS: The dosimetric findings, ease of application of the brachytherapy procedure, and the clinical results in early staged NPC, necessitates ERT combined with brachytherapy boost to be the therapy of preference for LD and LRD. For locally advanced T3,4 tumors, our current protocol indicates neoadjuvant chemotherapy in conjunction with high cumulative doses of radiotherapy (81Gy); IMRT and/or SRT to be the preferred technique for boosting the primary tumor.

Role of endocavitary brachytherapy with or without chemotherapy in cancer of the nasopharynx.

PURPOSE: We previously reported our preliminary experience with nasopharyngeal cancer boosted after 60-70 Gy external beam radiotherapy (EBRT) by fractionated endocavitary brachytherapy (ECBT) to cumulative doses of 78-82 Gy. As for Stage III-IVB disease, cisplatin (CDDP)-based neoadjuvant chemotherapy (CHT) was given. The aim of the present study was to define the role of ECBT more accurately. METHODS AND MATERIALS: Ninety-one patients with primary nasopharyngeal cancer, staged according to the 1997 UICC/AJCC classification system, were treated between 1991 and 2000 with 60-70 Gy external beam radiotherapy and 11-18 Gy ECBT. Of the 91 patients, 21 were treated in conjunction with CHT and 70 without CHT. Tumors were subdivided into undifferentiated (UD) and well, moderately, and poorly differentiated (WMP-D) subtypes. Treatment results were analyzed for local control (LC), disease-free survival (DFS), freedom from distant metastasis, and overall survival (OS). RESULTS: A univariate and multivariate Cox regression analysis found stage, treatment period, age, and grade significant for LC, DFS, and OS. At 2 years, for Stage I-IIB (1st period, 1991-1996), the LC, DFS, and OS were 96%, 88%, and 80%, respectively, vs. 65%, 46%, and 52% for Stage III-IVB. For the 2nd treatment period (1996-2000; CHT for Stage III-IVB), the LC, DFS, and OS at 2 years was 100%, 90%, and 61% (Stage I-IIB), respectively, vs. 86%, 74%, and 66% (Stage III-IVB). Three prognostic groups (PGs) were constructed. For the 1991-1996 period, at 2 years, patients in the good PG (UD Stage I-IIB disease) had 100% LC and 92% OS; those in the intermediate PG (UD Stage III-IVB or WMP-D Stage I-IIB), had 94% LC and 71% OS; and those in the poor PG (WMP-D Stage III-IVB) had 47% LC and 40% OS. For the 1996-2000 period, at 2 years, the good PG had 100% LC and 88% OS; the intermediate PG had 100% LC and 64% OS; and the poor PG had 71% LC and 60% OS. CONCLUSION: For Stage I-IIB disease treated between 1991 and 2000, at 3 years, the LC and OS was 97% and 67%, respectively. The results with 77-81 Gy without CHT warrant EBRT combined with ECBT to remain our standard of care for Stage I-IIB disease. For N2-3 and/or T3-4 tumors, in addition to high doses of RT, neoadjuvant CHT was administered as of 1996. For the 1991-2000 period, at 3 years, the LC was 86% and the OS was 72% with CHT, with little extra morbidity; they were 68% and 35% without CHT. Because of better target coverage and sparing, T3-4 tumors are currently boosted by stereotactic RT to 81.2 Gy.