Xerostomia Grade Research Articles

Impact of Salivary Gland Dosimetry on Post-IMRT Recovery of Saliva Output and Xerostomia Grade for Head-and-Neck Cancer Patients Treated With or Without Contralateral Submandibular Gland Sparing: A Longitudinal Study

To observe the recovery of saliva output and effect on xerostomia grade after intensity-modulated radiotherapy (IMRT) with or without contralateral submandibular gland (cSMG) sparing and to assess the impact of salivary gland dosimetry on this recovery among patients with head-and-neck cancer. Between May 2007 and May 2008, 52 patients with head-and-neck cancer received definitive (n=5 patients) and postoperative (n=47 patients) IMRT at our institution, with at least one parotid gland spared. Of these patients, 26 patients with a low risk of recurrence in the cSMG region underwent IMRT and had their cSMGs spared (cSMG-sparing group). The remaining 26 high-risk patients had no cSMGs spared (cSMG-unspared group). Xerostomia grades and salivary flow rates were monitored at five time points (before IMRT and at 2, 6, 12, and 18 months after IMRT). Average mean doses and mean volumes receiving 30 Gy (V30) of the cSMGs were lower in the cSMG-sparing group than in the cSMG-unspared group (mean dose, 20.4 Gy vs. 57.4 Gy; mean V30, 14.7% vs. 99.8%, respectively). Xerostomia grades at 2 and 6 months post-IMRT were also significantly lower among patients in the cSMG-sparing group than in the cSMG-unspared group, but differences were not significant at 12 and 18 months after IMRT. Patients in the cSMG-sparing group had significantly better mean unstimulated salivary flow rates at each time point post- IMRT as well as better mean stimulated salivary flow rates at 2 months post-IMRT. Recovery of saliva output and grade of xerostomia post-IMRT in patients whose cSMGs were spared were much better than in patients whose cSMGs were not spared. The influence of the mean doses to the cSMG and parotid gland on the recovery of saliva output was equivalent to that of the mean V30 to the glands.

SU‐GG‐J‐153: Voxel‐Based Phenomenological SUV‐Dose Response Model for the Human Parotid Glands

Purpose: The goal of this study is to evaluate SUV as an imaging biomarker of parotid function following radiotherapy (RT) and to develop a phenomenological model of SUV‐dose response, enabling prediction of the biomarker prior to RT. Method and Materials: As part of an ongoing study, patients (n = 8) with head and neck cancer (HNC) had 18F‐FDG PET/CT studies performed before (within 30 days) and following RT (∼50 days). In addition, resting and stimulated whole mouth saliva was collected. Next, a deformable image registration algorithm was utilized to map parotid contours from planning CT (PCT) images to pre‐ and post‐RT PET/CT studies, separately. Mean SUV was then calculated for the parotid glands at both time points and compared to collected saliva. The SUV‐dose response relationship was assessed in a separate cohort (n = 60) also treated for HNC. Pre‐ and post‐RT PET/CT images were deformably aligned to PCT images to achieve correspondence between SUV and planned dose. SUV response was then modeled using a single parameter, incorporating planned dose and pre‐RT SUV; defined as metabolic dose. Results: Post‐RT stimulated saliva and SUV decreased (59% and 20%, respectively) in seven patients. For one patient, stimulated saliva and SUV increased (14% and 11%, respectively). Fractional SUV correlated significantly with xerostomia grade, P < 0.01 and Spearman's ρ = −0.964. A second order polynomial provided an adequate fit to the log transformed SUV‐dose response curve, adjusted R2 = 0.95. Post‐RT SUV was predicted within 3% for an exemplary patient, but overestimated (50%) in the worst case. Conclusions: Pilot data suggest that SUV is significantly correlated with parotid saliva output. Furthermore, the feasibility of predicting reductions in SUV, prior to treatment delivery, has been demonstrated.Conflict of Interest: Research partially sponsored by Varian Medical Systems.

Multi-Institutional Trial of Accelerated Hypofractionated Intensity-Modulated Radiation Therapy for Early-Stage Oropharyngeal Cancer (RTOG 00-22)

To assess the results of a multi-institutional study of intensity-modulated radiation therapy (IMRT) for early oropharyngeal cancer. Patients with oropharyngeal carcinoma Stage T1-2, N0-1, M0 requiring treatment of the bilateral neck were eligible. Chemotherapy was not permitted. Prescribed planning target volumes (PTVs) doses to primary tumor and involved nodes was 66 Gy at 2.2 Gy/fraction over 6 weeks. Subclinical PTVs received simultaneously 54-60 Gy at 1.8-2.0 Gy/fraction. Participating institutions were preapproved for IMRT, and quality assurance review was performed by the Image-Guided Therapy Center. 69 patients were accrued from 14 institutions. At median follow-up for surviving patients (2.8 years), the 2-year estimated local-regional failure (LRF) rate was 9%. 2/4 patients (50%) with major underdose deviations had LRF compared with 3/49 (6%) without such deviations (p = 0.04). All cases of LRF, metastasis, or second primary cancer occurred among patients who were current/former smokers, and none among patients who never smoked. Maximal late toxicities Grade >or=2 were skin 12%, mucosa 24%, salivary 67%, esophagus 19%, osteoradionecrosis 6%. Longer follow-up revealed reduced late toxicity in all categories. Xerostomia Grade >or=2 was observed in 55% of patients at 6 months but reduced to 25% and 16% at 12 and 24 months, respectively. In contrast, salivary output did not recover over time. Moderately accelerated hypofractionatd IMRT without chemotherapy for early oropharyngeal cancer is feasible, achieving high tumor control rates and reduced salivary toxicity compared with similar patients in previous Radiation Therapy Oncology Group studies. Major target underdose deviations were associated with higher LRF rate.

Unstimulated whole saliva flow rate in relation to sicca symptoms in Hungary

To assess the prevalence of xerostomia and the related oral and extraoral dryness symptoms in Hungary, to evaluate the association of those symptoms with the unstimulated whole saliva (UWS) flow rate, and to find correlation between the level of UWS flow rate and the oral health status of the questioned patients. A total of 600 patients between the age of 18 and 92 years, 265 male, 335 female, were selected in accordance with the current regional age and residence distribution scheme of the Hungarian Statistical Office. A questionnaire was designed to determine the subjective presence or absence of the sicca symptoms. UWS flow rate and the dental and periodontal status were determined. The percentages of subjective symptoms in the questioned subjects were oral dryness, 34%; reduced salivation, 11%; mucous saliva, 15%; dysphagia, 13%; glossopyrosis, 7%; dysphonia, 31%; dysgeusia, 9%; nasal dryness, 32%; ocular dryness, 21%; itching, 40% and xeroderma, 60%. Vaginal dryness was 14%, vaginal itching was 16% in the interviewed women. The grade of xerostomia, dysphagia, tiredness, and additionally the gingival bleeding index showed a negative correlation with the UWS flow rate. After all decayed, missing and filled teeth (DMF-T) mean values, gingival bleeding index and plaque index were significantly higher in hyposalivators, compared with those who had normal flow rates This cross sectional study, representative of the Hungarian population, clearly shows that one-third of the adult population suffers from xerostomia. The clinical severity of the xerostomia demonstrated a strong relationship with the lower levels of UWS flow rate. Reduced levels of UWS flow rate in this study were also shown to be associated with dysphagia, fatigue, and increased DMF-T numbers. The data show that oral dryness, its associated desiccation symptoms and its clinical manifestations are significant health problems in Hungary.

Compensator-based Intensity-modulated Radiotherapy in Head and Neck Cancer: Our Experience in Achieving Dosimetric Parameters and their Clinical Correlation

Aims To review the Batra Hospital and Medical Research Centre experience of using compensator-based intensity-modulated radiotherapy (IMRT) to treat head and neck cancer. Materials and methods Between October 2003 and August 2004, 18 patients underwent IMRT for head and neck cancer at our institution. IMRT was delivered using partial transmission high-resolution compensator blocks. Results With a median follow-up of 13.3 months, two patients had residual disease and two failed in the gross tumour volume (GTV). The complete response rate after surgical salvage was 94.5%. Both the locoregional relapse-free and disease-free survival rates were 81.8%. The target coverage in terms of average maximum, mean and minimum dose (in Gy) delivered was 78.6, 73.5 and 58.4 to the GTV–planning target volume, 82.3, 70.9 and 47.3 to clinical target volume 1 (CTV1) and 82.9, 66.2 and 29.6 to CTV2. The dose constraint of 30 Gy to less than 50% of the contralateral parotid volume was achieved in 12 (66.7%) patients. If the dose constraint was revised to 35 Gy, at least 50% of the parotid volume was spared in 17 (94.5%) patients. On average, 75% of the contralateral parotid volume received a dose less than 35 Gy in 13 (72.3%) patients with grade I xerostomia, whereas this was 49.3% in five (27.7%) patients with grade II xerostomia, and the difference was statistically significant ( P = 0.001). Conclusions In our initial experience, compensator-based IMRT is feasible with regard to target coverage and parotid volume sparing. The parotid volume dose has significant clinical implications on the grade of xerostomia. Our results invoke rethinking into the issues of the parotid volume dose constraint in our subpopulation.

Neoadjuvant paclitaxel plus carboplatin followed by concomitant radiochemotherapy in stage IVb nasopharyngeal carcinoma: Preliminary results

15521 Background: Nasopharyngeal cancer Is the first head and neck cancer in Morocco. undifferentiated carcinoma (WHO 3)is dominant. Loco regional advanced stages IVa and IVb (AJCC/UICC 1997) represents 60 to 78%. Classical treatment is neoadjuvant chemotherapy (3 courses of BEP protocol) followed by radiotherapy. Therapeutic results are characterised by a high rate of failure. For stage IVb failure is due to distant metastasis wich occur in 30 to 40% of cases needing more systemic therapy. The aim of this prospective study is to analyse for stage IVb the benefit of introducing paclitaxel associated to carboplatin as a neoadjuvante chemotherapy followed by chemoradiation in terms of reducing distant metastasis and improving local control. Tolerance of this protocol was also analysed. Methods: Between September 2003 and January 2004, a total of 33 previously untreated, histologically confirmed NPC adults, were enrolled in this study. The new protocol is based on 1-Four courses of neoadjuvant chemotherapy (1 course = paclitaxel: 175 mg/m2 day 1 + carboplatin: 300 mg/m2 day 1; 1 course every 21 days) 2-followed by a concomitant radiochemotherapy: -radiotherapy to a total dose of 65 gray -and low dose of cisplatine (30 mg/m2) delivered on a weekly schedule. Eligibility criteria were: histologically confirmed NPC, stage IVb, no prior treatment, and informed consent of patients. There were 21 male and 12 female patients and their ages ranged from 19 to 58 years. Results: The minimal follow up was 2 years. The 2 year DFS was 85% and the 2 year loco regional free survival was 91%. All patients completed radiotherapy. Neutropenia grade III-IV was observed in 6% without fever. According to NCI toxicity criteria, acute mucositis (due to radiation) grade 3 was observed in 15% and grade 2 in 24%. Xerostomia grade 1 was observed in 70%. Conclusion: This protocol is very effective with less toxicity. Radiation dose is reduced without decreasing local control rate. The 2 years DFS is increased with this protocol to 85%. No significant financial relationships to disclose.

Three-dimensional conformal radiotherapy for locally advanced (Stage II and worse) head-and-neck cancer: Dosimetric and clinical evaluation

To evaluate the dosimetric parameters of three-dimensional conformal radiotherapy (3D-CRT) in locally advanced head-and-neck tumors (Stage II and above) and the effects on xerostomia. A total of 49 patients with histologically proven squamous cell cancer of the head and neck were consecutively treated with 3D-CRT using a one-point setup technique; 17 had larynx cancer, 12 oropharynx, 12 oral cavity, and 6 nasopharynx cancer; 2 had other sites of cancer. Of the 49 patients, 41 received postoperative RT and 8 definitive treatment. Also, 13 were treated with cisplatin-based chemotherapy before and during RT; in 6 cases, 5-fluorouracil was added. The follow-up time was 484-567 days (median, 530 days). One-point setup can deliver 96% of the prescribed dose to the isocenter, to the whole planning target volume, including all node levels of the neck and without overdosages. The mean dose to the primary planning target volume was 49.54 +/- 4.82 Gy (51.53 +/- 5.47 Gy for larynx cases). The average dose to the contralateral parotid gland was approximately 38 Gy (30 Gy for larynx cases). The maximal dose to the spinal cord was 46 Gy. A Grade 0 Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer xerostomia score corresponded to a mean dose of 30 Gy to one parotid gland. A lower xerostomia score with a lower mean parotid dose and longer follow-up seemed to give rise to a sort of functional recovery phenomenon. Three dimensional-CRT in head-and-neck cancers permits good coverage of the planning target volume with about 10-11 segments and one isocenter. With a mean dose of approximately 30 Gy to the contralateral parotid, we observed no or mild xerostomia.

Importance of the Initial Volume of Parotid Glands in Xerostomia for Patients with Head and Neck Cancers Treated with IMRT

Our aim was to evaluate predictors of xerostomia in patients with head and neck cancers treated with intensity-modulated radiation therapy (IMRT). Thirty-three patients with pharyngeal cancer were evaluated for xerostomia after having been treated with IMRT. All patients were treated with whole-neck irradiation of 46-50 Gy by IMRT, followed by boost IMRT to the high-risk clinical target volume to a total dose of 56-70 Gy in 28-35 fractions (median, 68 Gy). For boost IMRT, a second computed tomography (CT-2) scan was done in the third to fourth week of IMRT. Xerostomia was scored 3-4 months after the start of IMRT. The mean doses to the contralateral and ipsilateral parotid glands were 24.0 +/- 6.2 and 30.3 +/- 6.6 Gy, respectively. Among the 33 patients, xerostomia of grades 0, 1, 2 and 3 was noted in one, 18, 12 and two patients, respectively. Although the mean dose to the parotid glands was not correlated with the grade of xerostomia, the initial volume of the parotid glands was correlated with the grade of xerostomia (P = 0.04). Of 17 patients with small parotid glands (< or =38.8 ml) on initial CT (CT-1), 11 (65%) showed grade 2 or grade 3 xerostomia, whereas only three (19%) of 16 patients with larger parotid glands showed grade 2 xerostomia (P < 0.05). The mean volume of the parotid glands on CT-1 was 43.1 +/- 15.2 ml, but decreased significantly to 32.0 +/- 11.4 ml (74%) on CT-2 (P < 0.0001). Initial volumes of the parotid glands are significantly correlated with the grade of xerostomia in patients treated with IMRT. The volume of the parotid glands decreased significantly during the course of IMRT.

Subcutaneous amifostine for reduction of radiation xerostomia in nasopharynx cancer: A prospective randomised study

8043 Background: Xerostomia is the most common long-term toxicity after radiation therapy (RT) for nasopharynx cancer (NPC). Amifostine (AF) has recognised benefit in reduction of radiation xerostomia for head and neck cancers. However, there has been no randomized study specifically addressing the impact of AF on RT for NPC, and data on the use of subcutaneous amifostine is limited. Methods: Treatment naïve NPC patients whose primary treatment was conventional RT without chemotherapy were randomized to either RT only or RT plus amifostine (RT+AF). Patients in RT+AF arm received subcutaneous amifostine 500mg before each RT treatment during a 6.6–8.6 week course of RT. Primary endpoint was RTOG acute (at 4 weeks after RT), and chronic (at 1 year after RT) xerostomia grade (proportion of grade 2 xerostomia). Secondary endpoints were total salivary flow rates and scoring on a 6-item xerostomia questionnaire. Planned sample size was 28 patients in each arm, to detect a 40% reduction of grade 2 or worse xerostomia (assumed to occur in >=80% of patients in Arm-RT) with 80% power for alpha=0.05. Results: 49 patients were recruited, 3 patients were withdrawn before commencement of treatment, four patients had died of metastatic NPC, including one before completion of RT. 45 patients were evaluable for acute xerostomia and 37 patients for chronic xerostomia. Patients in RT+AF had significantly less grade 2 chronic xerostomia (8/17 vs 19/20, p=0.002, Fisher’s Exact Test) while the acute xerostomia grades were similar in both arms. The scores on the xerostomia questionnaire and the total saliva flow rates were similar in both arms, both at the early post-RT and 1 year post-RT time points. Conclusions: Subcutaneous amifostine reduces the occurrence of severe xerostomia as assessed by RTOG grading at one year after RT for NPC. No significant financial relationships to disclose.

Is chemoradiation feasible for child nasopharyngeal carcinoma ?

8558 Background: Nasopharyngeal cancer is the first head and neck cancer in morocco. Children form is frequent representing 5 to 7% of all cases and is histologically dominated by the undifferentiated carcinoma (WHO 3). There is a high incidence of locoregionally advanced disease: stage IVa and IVb (AJCC/UICC 1997) represents 97% of total recruitment. Classical treatment is neoadjuvant chemotherapy (3 courses of BEP protocol) followed by radiotherapy for nasopharynx tumour and cervical nodes. Therapeutic results are characterised by a high rate of failure. For stage IVb failure is due to distant metastasis wich occur in 30 to 40% of cases needing more systemic therapy. For stage IVa the major cause of failure is local relapse wich occur in 40 to 50% of cases requiring more intensive local treatment strategies. The aim of this prospective study is to analyse for stage IVa the benefit for local control of adjunction of low dose weekly cisplatine concomitantly to radiotherapy. Tolerance of this protocol was also analysed. Methods: Between January 1999 and December 2002, a total of 31 previously untreated, histologically confirmed NPC childs, were treated in our center with a new protocol. The protocol is based on 3 courses of neoadjuvant chemotherapy (B.E.P)followed by a concomitant radiochemotherapy wich associate radiotherapy to a total dose of 65 to 70 gray and low dose of cisplatine (20 mg/m2) delivered on a weekly schedule. Eligibility criteria were: histologically confirmed undifferentiated carcinoma of nasopharynx, stage IVa, age less than 18 years and informed consent of patients, parents with approbation of ethic groupe. There were 19 female and 12 male patients and their ages ranged from 10 to 17 years. Results: The minimal follow up was 2 years. The 2 year disease free survival was 67% and the 2 year loco regional free survival was 77%. All patients completed radiotherapy. According to NCI toxicity criteria, acute mucositis (due to radiation) grade 3 was observed in 3% and grade 2 in 22%. Xerostomia grade 1 was observed in 32%. Conclusions: This protocol is tolerated and feasible. The 2 years DFS is increased with this protocol to 67%. These results will certainly change management of child nasopharyngeal carcinoma No significant financial relationships to disclose.

Importance of mean dose and initial volume of parotid glands in xerostomia of patients with head and neck cancers receiving imrt

To evaluate the predictors of xerostomia in the treatment of head and neck cancers treated with intensity-modulated radiation therapy (IMRT). Dosimetric parameters of the parotid glands are correlated to the grade of xerostomia. Between December 2000 and December 2003, 25 patients were evaluated for xerostomia after being treated definitively for head and neck cancers with IMRT. Of the 25 patients, 13 were nasopharyngeal cancer (NPC), six oropharyngeal cancers, and six hypopharyngeal cancers. Except for one non-Hodgkin lymphoma of nasopharynx, the remaining 24 tumors were squamous cell carcinomas. All of the patients were treated with whole neck irradiation to 46–50 Gy/23–25 fractions by IMRT, followed by boost IMRT to the GTV and high-risk CTV to a total dose of 66–70 Gy/33–35 fractions (median 68 Gy). For the boost IMRT, second CT-simulation was done for all patients when the patients received a total dose of 30–40 Gy. Most patients were treated by concurrent chemo-radiation therapy. Concurrent cisplatin (60–80mg/m2 x 2–3 times) was given for 10 patients with NPC, and weekly docetaxel of 15/m2 was given for 10 patients with oro-hypopharyngeal cancers. Xerostomia was scored according to the subjective assessment of RTOG/EORTC late salivary gland toxicity when acute mucositis subsided 3–4 months after the start of IMRT. Slight dryness without affecting quality of life correlated to grade-1 toxicity, and moderate dryness requiring a water bottle correlated to grade-2 toxicity. Severe dryness referred to patients with a profound change in quality of life resulting from xerostomia was grade 3. It was possible to reduce the mean dose to the contra-lateral parotid gland to 25.0 Gy ± 6.4 Gy by IMRT. The mean dose to the ipsi-lateral parotid gland was 31.0 Gy ± 6.9 Gy. Among the 25 patients, 15 patients showed grade-1 xerostomia 3–4 months after IMRT, and eight and two patients showed grade-2 and grade-3 toxicities, respectively. Correlation between the grade of xerostomia and various dosimetric parameters were analyzed by the Spearman rank correlation. The mean dose to the contra-lateral parotid gland was significantly correlated to the grade of xerostomia (p = 0.036). Interestingly, parotid glands regressed significantly during the course of IMRT. The mean volume of parotid glands in the initial CT simulation was 44.9 ± 16.3 cc, and it was significantly reduced to 32.5 cc ± 12.1 cc (73%) in the second CT simulation obtained at 3–4th week of IMRT (p < 0.0001). Of the nine patients with small parotid glands of less than 35 cc in the initial CT, four grade-2 and two grade-3 xerostomia (67%) were noted, while only four grade-2 xerostomia (25%) were noted out of the remaining 16 patients with larger parotid glands (p < 0.05). In the treatment of head and neck cancers, IMRT could reduce the dose to the parotid glands resulted in sparing salivary function. The mean dose to the contra-lateral parotid gland and initial volume of the parotid glands are predictors of xerostomia. In addition, volume of parotid glands reduced significantly during the course of IMRT. This means that the dosimetric parameters including mean parotid doses obtained by an initial CT simulation are not accurate enough

The role of amifostine in prophylaxis of radiotherapy induced mucositis and xerostomia in head and neck cancer

5568 Background: To evaluate the use of amifostine prophylactically in radiochemotherapy induced acute mucositis and xerostomia in patients with head and neck carcinoma. Methods: One hundred and seventy patients of head and neck carcinoma were randomized to receive radiochemotherapy with or without amifostine. All the patients were suffering from locally advanced malignancy. A total of 66–72 gy was delivered conventionally with 40 mg/m2 weekly cisplatin. Amifostine 250mg was infused 10 min. prior to RT for four days a week to the patients in study group. Parotid scintigraphy was done before starting the treatment and at 3,6,12 and 24 months after completion of treatment. Mucositis and xerostomia were evaluated using RTOG criteria. Disease control was assessed at each follow up for two years. Results: The control group experienced an earlier onset of mucositis than the study group. By the end of 2nd week 74/85 control patients experienced grade II mucositis while similar toxicity was observed in 64/85 in the study group (p=0.05). All the patients had grade 3 or 4 mucositis in the control group whereas such severity was seen in 75/85 patients in the control group (p<0.001). The post radiation recovery of mucositis was faster in study group. By the end of 5 weeks of completion of radiation therapy 73/85 and 64/85 had no mucositis in the study and control group respectively (p<0.001). At 3 months follow up xerostomia grade 2 or more was found in 42/85 in control group compared with 32/85 in study group (p=0.017). By the end of 12 months of treatment in study group 37/85 experienced grade 1 or no xerostomia as compared to 59/85 in the control groups (p=0.002). However, treatment result remained unaffected in the amifostine groups. There were 49/85 disease free patients in control group compared with 52/85 in the study group (p=0.987). Conclusions: Amifostine was effective in reducing the severity and it delayed the onset of mucositis, a side effect with concurrent radiochemotherapy in head and neck carcinoma. It also decreased the severity of delayed xerostomia. Amifostine does not alter the response or the survival. No significant financial relationships to disclose.

Phase II trial of subcutaneous amifostine in patients undergoing radiation therapy for head and neck cancer

The availability of subcutaneously (SC) administered amifostine may present an advantage for radioprotectant therapy in head and neck cancer patients. In a randomized phase II trial comparing SC amifostine versus no amifostine in 140 patients undergoing radiation therapy for head and neck, thoracic, or pelvic cancers, amifostine treatment was associated with reductions in mucosal toxicity and delays in radiation therapy among the 19 patients with head and neck cancer, as well as in the thoracic and pelvic cancer groups. A phase II trial of SC amifostine in head and neck cancer was performed in a patient population (n = 54) similar to that studied in a phase III trial of intravenous amifostine to allow comparisons of outcomes. Acute xerostomia grade 2 occurred in 56% with SC amifostine and 51% with intravenous amifostine (78% in the no-amifostine group in phase III trial), with median time to onset being 40 days and 45 days, respectively (30 days with no amifostine), and cumulative radiation dose to onset being 58 Gy and 60 Gy (42 Gy with no amifostine), respectively. Amifostine SC was well tolerated, with three quarters of patients receiving ≥75% of the planned dose. Nausea, vomiting, and hypotension were less severe with SC amifostine, but cutaneous toxicity was more frequent. The reduction in radiation therapy-induced acute xerostomia with SC amifostine is similar to that with intravenous amifostine in patients with head and neck cancer. If cutaneous toxicity is judged an acceptable risk, SC amifostine may represent a second, more convenient option for treating physicians. Semin Oncol 29 (suppl 19):80-83. Copyright 2002, Elsevier Science (USA). All rights reserved.

A randomized, double-blind, placebo-controlled trial of concomitant pilocarpine with head and neck irradiation for prevention of radiation-induced xerostomia

Background: Xerostomia is one of the disturbing side-effects of radiotherapy to the head and neck region. Pilocarpine has been approved for the treatment of this condition in the chronic phase, but its use concurrent with radiation could also be beneficial for prevention or reduction of the subsequent radiation-induced xerostomia. We undertook to test this hypothesis in a clinical trial. Methods: At the start of radiotherapy, randomization was performed to either pilocarpine 5 mg three times daily or placebo in a double-blind setting. The drug was started with irradiation and continued until 3 months after the end of radiotherapy. Xerostomia was evaluated 6 months after the end of radiation by a subjective visual analog scale questionnaire. Also the objective grade of xerostomia was recorded by two separate observers. Results: A total number of 60 patients were randomized into the trial, but unfortunately only 39 patients were finally evaluated for xerostomia, 18 in the pilocarpine and 21 in the placebo group. Mean age was 42 years, and mean parotid dose was 58 Gy. Mean subjective xerostomia was 40.3 mm in the pilocarpine group and 57 mm in the placebo group ( P=0.02). Also mean objective xerostomia grade was 2.2 in the pilocarpine group and 2.6 in the placebo group ( P=0.01). Subjective and objective xerostomia results were positively correlated ( P=0.01). Age and the parotid dose did not have a significant effect on xerostomia. Conclusions: Compared to placebo, pilocarpine used with radiotherapy could lead to a significant diminishment of subsequent radiation-induced xerostomia.

Assessment of salivary gland dysfunction following chemoradiotherapy using quantitative salivary gland scintigraphy

Purpose:To assess chemoradiotherapy-induced salivary gland dysfunction using quantitative salivary gland scintigraphy (QSGS), and whether QSGS is capable of predicting the grade of persistent salivary dysfunction after chemoradiotherapy.Methods: From a time–activity curve using a stimulation test, the washout rate (WR) calculated was assessed. All glands (n = 155) were classified into four groups: a no-therapy group (n = 18), a chemotherapy alone group (n = 31), a radiotherapy alone group (n = 50), and a chemoradiotherapy group (n = 56). Subjective descriptions of xerostomia were recorded 1 year after the completion of the treatment period, and the 32 glands subjected to irradiation with or without chemotherapy were assessed.Results: The WR values were significantly lower in glands that received chemoradiotherapy than in glands treated with radiotherapy alone (mean: 0.75 × 10-3, n = 40 vs. 0.22, n = 36, p < 0.015), but there was no significant difference in the WR values between the no-therapy group and the chemotherapy alone group. The mean values of WR were lower in the chemoradiotherapy glands than in the radiotherapy alone glands in each of cumulative dose ranges of 1–20, 21–30, and 31–60 Gy. With regard to recovery from xerostomia, the WR values at a cumulative dose range of 20 to 40 Gy were significantly lower in the not improved group (−0.418, n = 16) than in the improved group (0.245, n = 16) (p < 0.0001).Conclusion: Chemotherapy per se has no or little adverse effect on salivary function, but combination chemotherapy can deteriorate radiation-induced injury of the salivary glands. QSGS appears useful in predicting the grade of persistent xerostomia following chemoradiotherapy.