Recurrences after conformal parotid-sparing radiotherapy for head and neck cancer.

BACKGROUND AND PURPOSE: Evaluation of loco-regional failure patterns and survival after parotid-sparing three-dimensional conformal and intensity modulated radiotherapy (IMRT) for head and neck cancer. PATIENTS AND METHODS: From June 1999 to July 2002, seventy-two patients with lateralised head and neck tumours, excluding nasopharyngeal tumours and patients with bilateral or contralateral neck disease, were irradiated with a parotid-sparing technique. Three-dimensional conformal planning was used in 68 patients, 4 patients were treated with dynamic IMRT. Bilateral neck node irradiation was performed in all patients, the junctional (or high level II) nodes, contralateral to the tumour, however, were excluded from the clinical target volume to spare the adjacent parotid from irradiation. In 20 patients with persistent or recurrent loco-regional disease, the localisation and volume of the treatment failure, as determined by computed tomography (CT), was copied on the pre-treatment CT-study used for treatment planning. Minimum, mean and maximum doses administered to the region of the failure were calculated and dose--volume histograms were computed of each failure. The failures were divided in three groups depending on the percentage of their volume receiving 95% of the prescribed dose. Recurrences were defined to be in-field (IF) if >95% of their volume received 95% of the prescribed dose and out-field (OF) if <20% of their volume received 95% of the prescribed dose. When 20-95% of the volume of the recurrence received 95% of the prescribed dose, this recurrence was defined as extending outside the field (EOF). RESULTS: With a median follow-up time of 19 months, the 2-year loco-regional control rate was 69% with primary radiotherapy and 63.5% with surgery followed by irradiation (P = 0.77). The 2-year overall survival rate for the entire patient population was 67.4%. At the time of analysis, 20 of the 72 patients had developed a loco-regional failure; 2 patients (2/20) presented with a loco-regional relapse combined with distant metastasis. Fifteen of the 20 loco-regional failures (15/20) occurred within the high dose region (IF). Five patients (5/20) developed a failure of which the bulky tumour mass was located within the high dose region but extending outside the treatment volume (EOF). No relapses were seen out-field (OF) and no patients relapsed in the spared junctional area contralateral to the tumour. CONCLUSIONS: The selection of patients treated with parotid-sparing radiotherapy, by omitting irradiation to the junctional nodes contralateral to the tumour, proved to be safe in our hands, since no recurrences developed in the spared area. As this parotid-sparing technique reduces significantly the dose to the contralateral parotid and is easy to perform, it should be considered for all selected patients.     

Preserved salivary output and xerostomia-related quality of life in head and neck cancer patients receiving parotid-sparing radiotherapy

Radiotherapy (RT) for head and neck cancers causes salivary dysfunction and diminished xerostomia-related quality of life. We have demonstrated that three-dimensional treatment planning and conformational dose-delivery techniques can minimize RT doses to contralateral parotid glands while providing therapeutic doses to tumors. This study's purpose was to assess parotid salivary function up to 1 year post-RT in patients receiving bilateral neck parotid-sparing RT, and to determine if parotid preservation would significantly improve xerostomia-related quality of life. Unstimulated (UPFR) and stimulated (SPFR) parotid flow rates were collected from 20 head and neck cancer patients. All subjects completed a 15-item xerostomia-related quality of life scale (XeQoLS) prior to RT, at the completion of RT, 1, 3, 6 and 12 months post-RT. Salivary flow rates from spared and treated glands were significantly decreased at the completion of RT. After RT completion, spared UPFR and SPFR function increased and was not significantly different from baseline values. Output from treated glands remained statistically indistinguishable from zero throughout the post-RT period. Subjects had a significantly worse xerostomia-related quality of life at the completion of RT compared to baseline, and XeQoLS responses improved significantly 1 month post-RT. Responses at 1 year were markedly better than at the completion of RT, but still significantly worse than baseline. These findings suggest that despite parotid-sparing RT, salivary flow rates from treated and spared glands and xerostomia-related quality of life decrease at the completion of RT. However, with the use of parotid-sparing RT, contralateral glands are preserved at 1 year post-RT with a concomitant improvement in xerostomia-related quality of life.     

Management of xerostomia related to radiotherapy for head and neck cancer

Xerostomia is a permanent and devastating sequela of head and neck irradiation, and its consequences are numerous. Pharmaceutical therapy attempts to preserve or salvage salivary gland function through systemic administration of various protective compounds, most commonly amifostine (Ethyol) or pilocarpine. When these agents are ineffective or the side effects too bothersome, patients often resort to palliative care, for example, with tap water, saline, bicarbonate solutions, mouthwashes, or saliva substitutes. A promising surgical option is the Seikaly-Jha procedure, a method of preserving a single submandibular gland by surgically transferring it to the submental space before radiotherapy. Improved radiation techniques, including intensity-modulated radiotherapy and tomotherapy, allow more selective delivery of radiation to defined targets in the head and neck, preserving normal tissue and the salivary glands. Acupuncture may be another option for patients with xerostomia. All of these therapies need to be further studied to establish the most effective protocol to present to patients before radiotherapy has begun.     

Two-year longitudinal study of parotid salivary flow rates in head and neck cancer patients receiving unilateral neck parotid-sparing radiotherapy treatment

Radiotherapy (RT) is a common treatment for head and neck cancers, and frequently causes permanent salivary dysfunction and xerostomia. This 2-year longitudinal study evaluated unstimulated and stimulated parotid flow rates in 11 patients with head and neck cancers who received unilateral neck parotid-sparing RT. The results demonstrated that treated parotid glands had essentially no output up to 2 years post-RT. Alternatively, spared parotid flow rates were indistinguishable from pre-RT values at 1 and 2 years post-RT, and increased slightly over time. Total unstimulated and stimulated parotid flow rates 2 years after completion of RT were similar to pre-RT values, suggesting that spared parotid function may compensate for lost function from treated parotid glands. These results demonstrate that unilateral neck parotid-sparing techniques are effective in preserving contralateral parotid glands up to 2 years after the completion of RT.     

Patterns of local-regional recurrence following parotid-sparing conformal and segmental intensity-modulated radiotherapy for head and neck cancer

Purpose: To analyze the patterns of local-regional recurrence in patients with head and neck cancer treated with parotid-sparing conformal and segmental intensity-modulated radiotherapy (IMRT).

Methods and Materials: Fifty-eight patients with head and neck cancer were treated with bilateral neck radiation (RT) using conformal or segmental IMRT techniques, while sparing a substantial portion of one parotid gland. The targets for CT-based RT planning included the gross tumor volume (GTV) (primary tumor and lymph node metastases) and the clinical target volume (CTV) (postoperative tumor bed, expansions of the GTVs and lymph node groups at risk of subclinical disease). Lymph node targets at risk of subclinical disease included the bilateral jugulodigastric and lower jugular lymph nodes, bilateral retropharyngeal lymph nodes at risk, and high jugular nodes at the base of skull in the side of the neck at highest risk (containing clinical neck metastases and/or ipsilateral to the primary tumor). The CTVs were expanded by 5 mm to yield planning target volumes (PTVs). Planning goals included coverage of all PTVs (with a minimum of 95% of the prescribed dose) and sparing of a substantial portion of the parotid gland in the side of the neck at less risk. The median RT doses to the gross tumor, the operative bed, and the subclinical disease PTVs were 70.4 Gy, 61.2 Gy, and 50.4 Gy respectively. All recurrences were defined on CT scans obtained at the time of recurrence, transferred to the pretreatment CT dataset used for RT planning, and analyzed using dose–volume histograms. The recurrences were classified as 1) “in-field,” in which 95% or more of the recurrence volume (V_recur) was within the 95% isodose; 2) “marginal,” in which 20% to 95% of V_recur was within the 95% isodose; or 3) “outside,” in which less than 20% of V_recur was within the 95% isodose.

Results: With a median follow-up of 27 months (range 6 to 60 months), 10 regional recurrences, 5 local recurrences (including one noninvasive recurrence) and 1 stomal recurrence were seen in 12 patients, for a 2-year actuarial local-regional control rate of 79% (95% confidence interval 68–90%). Ten patients (80%) relapsed in-field (in areas of previous gross tumor in nine patients), and two patients developed marginal recurrences in the side of the neck at highest risk (one in the high retropharyngeal nodes/base of skull and one in the submandibular nodes). Four regional recurrences extended superior to the jugulodigastric node, in the high jugular and retropharyngeal nodes near the base of skull of the side of the neck at highest risk. Three of these were in-field, in areas that had received the dose intended for subclinical disease. No recurrences were seen in the nodes superior to the jugulodigastric nodes in the side of the neck at less risk, where RT was partially spared.

Conclusions: The majority of local-regional recurrences after conformal and segmental IMRT were “in-field,” in areas judged to be at high risk at the time of RT planning, including the GTV, the operative bed, and the first echelon nodes. These findings motivate studies of dose escalation to the highest risk regions.     

Impact of radiation-induced xerostomia on quality of life after primary radiotherapy among patients with head and neck cancer

PURPOSE: To investigate the impact of xerostomia on overall quality of life (QoL) outcome and related dimensions among head and neck cancer patients treated with primary radiotherapy. METHODS AND MATERIALS: A total of 288 patients with Stage I-IV disease without distant metastases were included. Late xerostomia according to the Radiation Therapy Oncology Group (RTOG-xerostomia) and QoL (European Organization for Research and Treatment of Cancer QLC-C30) were assessed at baseline and every 6th month from 6 months to 24 months after radiotherapy. RESULTS: A significant association was found between RTOG-xerostomia and overall QoL outcome (effect size [ES] 0.07, p < 0.001). A significant relationship with global QoL, all functioning scales, and fatigue and insomnia was observed. A significant interaction term was present between RTOG-xerostomia and gender and between RTOG-xerostomia and age. In terms of gender, RTOG-xerostomia had a larger impact on overall QoL outcome in women (ES 0.13 for women vs. 0.07 for men). Furthermore, in women ES on individual scales were larger, and a marked worsening was observed with increasing RTOG-xerostomia. No different ES according to age was seen (ES 0.10 for 18-65 years vs. 0.08 for >65 years). An analysis of the impact of RTOG-xerostomia on overall QoL outcome over time showed an increase from 0.09 at 6 months to 0.22 at 24 months. With elapsing time, a worsening was found for these individual scales with increasing RTOG-xerostomia. CONCLUSIONS: The results of this prospective study are the first to show a significant impact of radiation-induced xerostomia on QoL. Although the incidence of Grade > or =2 RTOG-xerostomia decreases with time, its impact on QoL increases. This finding emphasizes the importance of prevention of xerostomia.     

Radiation-induced xerostomia in patients with head and neck cancer: a literature review

A dry mouth or xerostomia is one of the most common complications during and after radiotherapy for head and neck cancer, because irreparable damage is caused to the salivary glands, which are included in the radiation fields. Xerostomia not only significantly impairs the quality of life of potentially cured cancer patients, it may also lead to severe and long-term oral disorders. Because management of xerostomia is rarely effective, prevention is paramount. Several strategies have been developed to avoid radiation-induced salivary dysfunction without compromising definitive oncologic treatment. These include salivary gland-sparing radiation techniques, such as 3-dimensional conformal or intensity-modulated radiotherapy, concomitant cytoprotectants, and surgical salivary gland transfer. However, these preventive approaches are not applicable to all patients, and comprehensive scientific research that incorporates new biological insights is warranted to optimize the therapeutic index of radiotherapy for head and neck cancer.     

Acupuncture for pilocarpine-resistant xerostomia following radiotherapy for head and neck malignancies

OBJECTIVE: Xerostomia is a frequent and potentially debilitating toxicity of radiotherapy (XRT) for cancers of the head and neck. This report describes the use of acupuncture as palliation for such patients. METHODS AND MATERIALS: Eighteen patients with xerostomia refractory to pilocarpine therapy after XRT for head and neck malignancy were offered acupuncture as palliation. All patients are without evidence of cancer recurrence at the primary site. Acupuncture was provided to three auricular points and one digital point bilaterally, with electrostimulation used variably. The Xerostomia Inventory (XI) was administered retrospectively to provide an objective measure of efficacy. RESULTS: Acupuncture contributed to relief from xerostomia to varying degrees. Palliative effect as measured by the XI varied from nil to robust (pre- minus post- therapy values of over 20 points). Nine patients had benefit of over 10 points on the XI. CONCLUSIONS: Acupuncture reduces xerostomia in some patients who are otherwise refractory to best current management.     

The efficacy of Xialine in patients with xerostomia resulting from radiotherapy for head and neck cancer: a pilot-study.

Changes in subjective sensations due to xerostomia before and after administration of Xialine, a xanthan gum-based saliva substitute, were evaluated in 30 patients with radiation-induced xerostomia using the QLQ-H&N35. Xerostomia in general decreased with both Xialine and placebo to almost the same degree. A trend was seen for Xialine to improve problems with speech and senses.     

Cevimeline for the treatment of postirradiation xerostomia in patients with head and neck cancer

PURPOSE: To study the efficacy and safety of cevimeline in two double-blind trials (Studies 003 and 004) enrolling patients with head and neck cancer in whom xerostomia developed after radiotherapy. METHODS AND MATERIALS: Subjects were randomly assigned to receive cevimeline, 30 mg three times daily, or placebo for 12 weeks, with the possibility of dose escalation to 45 mg three times daily at 6 weeks. The primary efficacy endpoint was the patient's final global evaluation of oral dryness; change in unstimulated salivary flow was a secondary endpoint. RESULTS: Five hundred seventy subjects (284 in Study 003 and 286 in Study 004) were randomized. Significantly more cevimeline-treated subjects than placebo recipients (47.4% vs. 33.3%, p = 0.0162) in Study 003 reported improvement in dry mouth in the final global evaluation of oral dryness. No significant difference between groups in the final global evaluation was seen in Study 004, in which a high placebo response rate of 47.6% was observed. In both studies, cevimeline-treated subjects had significantly greater increases in the objective measure of unstimulated salivary flow than placebo recipients (p = 0.0093 [Study 003] and p = 0.0215 [Study 004]), whereas no significant differences in stimulated salivary flow were observed. The most frequent adverse event was increased sweating. CONCLUSION: Cevimeline was well tolerated by patients with xerostomia after radiotherapy for head and neck cancer, and oral administration of 30-45 mg of cevimeline three times daily increased unstimulated salivary flow.     

Contralateral parotid-sparing radiotherapy in patients with unilateral squamous cell carcinoma of the head and neck: technical methodology and preliminary results

AIMS AND BACKGROUND: Radiation-induced permanent xerostomia occurs frequently in patients affected by squamous cell carcinoma of the head and neck treated by parallel opposed lateral fields. An ipsilateral technique by using co-planar multiple-field arrangement was designed to restrict treatment to the primary tumor and neck on the same side for patients with selected lateralized squamous cell carcinoma of the head and neck. METHODS: From November 2001 till December 2002, 30 patients affected by squamous cell carcinoma of tonsillar fossa, retromolar trigone, alveolar ridge and oropharyngeal lateral wall were included in this investigational trial and treated with an ipsilateral multiple field technique: in detail, oblique opposed two upper half fields were planned ipsilaterally to the squamous cell carcinoma site to cover PTV1 and PTV2, whereas an anterior-lower half field was planned to encompass the lower neck node area above clavicles. On CT scans, the contralateral parotid gland was outlined as organ at risk and the contralateral upper lymph node area was contoured as volume of interest. In selected cases, convergent oblique two wedge-pair half fields were added to opposed oblique two-field technique in order to cover only PTV2: generally, in these patients, PTV1 received 1.8 Gy per fraction and PTV2 2.2 Gy per fraction up to total doses of 54 Gy and 66 Gy, respectively. RESULTS: Ten patients received radical radiotherapy, 9 patients radical alternating chemo-radiotherapy, and 11 patients adjuvant radiotherapy. At the end of treatment, unilateral confluent mucositis was recorded in 13 (43%) patients and unilateral moist skin epidermolysis in 14 (46%) patients. Six months after the end of radiotherapy, grade 0 xerostomia was recorded in 20 (67%) patients. No patient experienced grade 2+ xerostomia. At a median follow-up of 12 months, 26 (86%) patients were alive and well; 2 patients (6%) developed contralateral neck node failure, both 4 months after the end of ipsilateral radiotherapy. CONCLUSIONS: These results, although preliminary, suggest that by using an ipsilateral radiotherapy technique, symptomatic xerostomia may be avoided in selected patients with lateralized squamous cell carcinoma of the head and neck without an increased short-term risk of contralateral nodal failure.     

头颈部肿瘤放疗对甲状腺功能的损伤

头颈部肿瘤放疗后会引起不同程度的甲状腺功能减退.引起甲状腺功能减退的机制包括射线对甲状腺及垂体细胞的直接损伤、对相关血管的损伤以及自身免疫反应等.影响头颈部肿瘤放疗后甲状腺功能的因素主要有:放疗剂量、放疗技术、是否联合手术化疗等.通过对这些影响因素的研究可为防治甲状腺功能减退提供依据,从而提高患者生活质量.     

头颈部肿瘤放疗对甲状腺功能的损伤

头颈部肿瘤放疗后会引起不同程度的甲状腺功能减退.引起甲状腺功能减退的机制包括射线对甲状腺及垂体细胞的直接损伤、对相关血管的损伤以及自身免疫反应等.影响头颈部肿瘤放疗后甲状腺功能的因素主要有:放疗剂量、放疗技术、是否联合手术化疗等.通过对这些影响因素的研究可为防治甲状腺功能减退提供依据,从而提高患者生活质量.     

头颈部肿瘤放疗对甲状腺功能的损伤

头颈部肿瘤放疗后会引起不同程度的甲状腺功能减退.引起甲状腺功能减退的机制包括射线对甲状腺及垂体细胞的直接损伤、对相关血管的损伤以及自身免疫反应等.影响头颈部肿瘤放疗后甲状腺功能的因素主要有:放疗剂量、放疗技术、是否联合手术化疗等.通过对这些影响因素的研究可为防治甲状腺功能减退提供依据,从而提高患者生活质量.     

头颈部肿瘤放疗对甲状腺功能的损伤

头颈部肿瘤放疗后会引起不同程度的甲状腺功能减退.引起甲状腺功能减退的机制包括射线对甲状腺及垂体细胞的直接损伤、对相关血管的损伤以及自身免疫反应等.影响头颈部肿瘤放疗后甲状腺功能的因素主要有:放疗剂量、放疗技术、是否联合手术化疗等.通过对这些影响因素的研究可为防治甲状腺功能减退提供依据,从而提高患者生活质量.     

头颈部肿瘤放疗对甲状腺功能的损伤

头颈部肿瘤放疗后会引起不同程度的甲状腺功能减退.引起甲状腺功能减退的机制包括射线对甲状腺及垂体细胞的直接损伤、对相关血管的损伤以及自身免疫反应等.影响头颈部肿瘤放疗后甲状腺功能的因素主要有:放疗剂量、放疗技术、是否联合手术化疗等.通过对这些影响因素的研究可为防治甲状腺功能减退提供依据,从而提高患者生活质量.     

头颈部肿瘤放疗对甲状腺功能的损伤

头颈部肿瘤放疗后会引起不同程度的甲状腺功能减退.引起甲状腺功能减退的机制包括射线对甲状腺及垂体细胞的直接损伤、对相关血管的损伤以及自身免疫反应等.影响头颈部肿瘤放疗后甲状腺功能的因素主要有:放疗剂量、放疗技术、是否联合手术化疗等.通过对这些影响因素的研究可为防治甲状腺功能减退提供依据,从而提高患者生活质量.