Mild Xerostomia Research Articles

225 Ac-PSMA-617 Augmentation in High-Risk mCRPC Undergoing 177 Lu-PSMA-617 Radioligand Therapy : Pilot Experience From a Prospective Registry.

This pilot study investigates the efficacy and safety profile as well as predictive biomarkers of 225 Ac-PSMA-617-augmented 177 Lu-PSMA-617 radioligand therapy (RLT) in a cohort of high-risk patients with metastatic castration-resistant prostate cancer (mCRPC), enrolled in a prospective registry (NCT04833517). A group of n = 33 high-risk mCRPC patients received 177 Lu-PSMA-617 RLT, augmented by 1 or more cycles of 225 Ac-PSMA-617. Response was assessed by prostate-specific antigen (PSA) serum value after 2 cycles of treatment. Overall survival (OS) and PSA-based progression-free survival were evaluated using Kaplan-Meier analysis. To assess the side effect profile, Common Terminology Criteria for Adverse Events were applied. In total, 12 potential pretherapeutic biomarkers were tested for association with OS. The median decrease in serum PSA value was -49.1%, and 16/33 (48.5%) patients experienced a partial response after 2 cycles RLT. The median PSA-based progression-free survival and median OS was 7.2 and 14.8 months, respectively. Alkaline phosphatase ( P < 0.001), lactate dehydrogenase ( P = 0.035), Eastern European Oncology Group Performance Score ( P = 0.037), and the presence of visceral metastases ( P = 0.029) revealed significant association with OS in Kaplan-Meier analysis (log-rank test). Most of the recorded adverse events were rated as mild or moderate. Higher-grade adverse events were very limited with only 1 case (3.0%) of grade 3 anemia. Treatment-related mild xerostomia was recorded in 6/33 (18.2%) patients. 225 Ac-PSMA-617 augmentation in high-risk mCRPC undergoing 177 Lu-PSMA-617 RLT appears to be an effective treatment option with a favorable safety profile. The pretherapeutic values of alkaline phosphatase, lactate dehydrogenase, the Eastern European Oncology Group Performance Score, and the presence of visceral metastases may be appropriate biomarkers predicting survival outcome of this treatment regimen.

Morphological, Functional and Texture Analysis Magnetic Resonance Imaging Features in the Assessment of Radiotherapy-Induced Xerostomia in Oropharyngeal Cancer

The aim of this single-center, observational, retrospective study was to investigate magnetic resonance imaging (MRI) biomarkers for the assessment of radiotherapy (RT)-induced xerostomia. Twenty-seven patients who underwent radiation therapy for oropharyngeal cancer were divided into three groups according to the severity of their xerostomia—mild, moderate, and severe—clinically confirmed with the Common Terminology Criteria for Adverse Events (CTCAE). No severe xerostomia was found. Conventional and functional MRI (perfusion- and diffusion- weighted imaging) performed both pre- and post-RT were studied for signal intensity, mean apparent diffusion coefficient (ADC) values, k-trans, and area under the perfusion curves. Contrast-enhanced T1 images and ADC maps were imported into 3D slicer software, and salivary gland volumes were segmented. A total of 107 texture features were derived. T-Student and Wilcoxon signed-rank tests were performed on functional MRI parameters and texture analysis features to identify the differences between pre- and post-RT populations. A p-value &lt; 0.01 was defined as acceptable. Receiver operating characteristic (ROC) curves were plotted for significant parameters to discriminate the severity of xerostomia in the pre-RT population. Conventional and functional MRI did not yield statistically significant results; on the contrary, five texture features showed significant variation between pre- and post-RT on the ADC maps, of which only informational measure of correlation 1 (IMC 1) was able to discriminate the severity of RT-induced xerostomia in the pre-RT population (area under the curve (AUC) &gt; 0.7). Values lower than the cut-off of −1.473 × 10−11 were associated with moderate xerostomia, enabling the differentiation of mild xerostomia from moderate xerostomia with a 73% sensitivity, 75% specificity, and 75% diagnostic accuracy. Therefore, the texture feature IMC 1 on the ADC maps allowed the distinction between different degrees of severity of RT-induced xerostomia in the pre-RT population. Accordingly, texture analysis on ADC maps should be considered a useful tool to evaluate salivary gland radiosensitivity and help identify patients at risk of developing more serious xerostomia before radiation therapy is administered.

Transfer learning approach based on computed tomography images for predicting late xerostomia after radiotherapy in patients with oropharyngeal cancer.

Background and purposeAlthough the latest breakthroughs in radiotherapy (RT) techniques have led to a decrease in adverse event rates, these techniques are still associated with substantial toxicity, including xerostomia. Imaging biomarkers could be useful to predict the toxicity risk related to each individual patient. Our preliminary work aims to develop a radiomic-based support tool exploiting pre-treatment CT images to predict late xerostomia risk in 3 months after RT in patients with oropharyngeal cancer (OPC).Materials and methodsWe performed a multicenter data collection. We enrolled 61 patients referred to three care centers in Apulia, Italy, out of which 22 patients experienced at least mild xerostomia 3 months after the end of the RT cycle. Pre-treatment CT images, clinical and dose features, and alcohol-smoking habits were collected. We proposed a transfer learning approach to extract quantitative imaging features from CT images by means of a pre-trained convolutional neural network (CNN) architecture. An optimal feature subset was then identified to train an SVM classifier. To evaluate the robustness of the proposed model with respect to different manual contouring practices on CTs, we repeated the same image analysis pipeline on “fake” parotid contours.ResultsThe best performances were achieved by the model exploiting the radiomic features alone. On the independent test, the model reached median AUC, accuracy, sensitivity, and specificity values of 81.17, 83.33, 71.43, and 90.91%, respectively. The model was robust with respect to diverse manual parotid contouring procedures.ConclusionRadiomic analysis could help to develop a valid support tool for clinicians in planning radiotherapy treatment, by providing a risk score of the toxicity development for each individual patient, thus improving the quality of life of the same patient, without compromising patient care.

Diffusion-weighted imaging as a\xa0follow-up modality for evaluation of major salivary gland function in nasopharyngeal carcinoma patients: a\xa0preliminary study

PurposeTo investigate the value of diffusion-weighted imaging (DWI) in assessing dynamic changes of major salivary gland function during follow-up post radiotherapy (RT) in nasopharyngeal carcinoma (NPC) patients.Materials and methods31 consecutive patients with pathologically confirmed NPC scheduled for RT underwent six routine follow-up MRI examinations including DWI sequence prior to (pre-RT) and 1, 3, 6, 9, and 12 months post RT. Mean apparent diffusion coefficient (ADC) values of bilateral parotid glands (PGs) and submandibular glands (SMGs) were measured. Objective measurement of salivary flow rate (SFR) under unstimulated (uSFR) and stimulated conditions (sSFR) as well as subjective xerostomia assessment according to a patient-rated questionnaire were conducted before each MRI. Variance analysis was used to evaluate dynamic changes of ADC, SFR and xerostomia questionnaire summary scores (XQ-sum) at different timepoints and the correlation between ADC and XQ-sum. Pearson’s correlation test was used to evaluate the correlations between pre- and post-RT changes of ADC (ΔADC) and SFR (ΔSFR) or mean RT dose.ResultsAt each timepoint, ADCs of PGs were significantly lower than of SMGs, uSFR was significantly lower than sSFR. For both PGs and SMGs, ADCpost-RT were all higher than ADCpre-RT, with significant differences. ADC1m-post-RT initially increased and changed little to ADC3m-post-RT, ADC6m-post-RT, ADC9m-post-RT, and ADC12m-post-RT, then gradually declined over time. The dynamic change trends of SFR were negatively paralleled to those of ADC, while that of XQ-sum was similar. Dose–response relationships were detected between salivary gland mean RT dose and ΔADC. In PGs, negative correlations between ΔsSFR9m-post-RT and ΔADC9m-post-RT, and ΔsSFR12m-post-RT and ΔADC12m-post-RT were detected. In SMGs, negative correlations between ΔsSFR12m-post-RT and ΔADC12m-post-RT, and ΔuSFR12m-post-RT and ΔADC12m-post-RT were also detected. The ADCs of patients with severe subjective xerostomia were significantly higher, while patients with moderate subjective xerostomia presented a tendency toward higher ADCs compared to those with mild xerostomia from 6 to 12 months post RT.ConclusionAs part of routine follow-up MRI in NPC patients, DWI might be a promising modality for follow-up assessing the dynamic changes of major salivary gland function and might be more powerful in the late post-RT period.

PENERAPAN PEMBERIAN PERMEN KARET XYLITOL UNTUK XEROSTOMIA PADA PASIEN PENYAKIT GINJAL KRONIS DI RUMAH SAKIT TK. III 04.06.02 BHAKTI WIRA TAMTAMA SEMARANG

Hemodialysis is an action used in kidney failure patients to remove and clean up metabolic waste substances and other toxic substances. So you have to undergo hemodialysispatients undergoing hemodialysis must be limited to administration of fluids. The consequences of fluid restriction can lead to complaints of thirst and xerostomia. Giving xylitol gum can stimulate saliva to overcome xerostomia. The purpose of this case study is to describe the application of xylitol gum to reduce xerostomia in patients. The method used in this study is Quasy Experiment. The instrument used was SXI-D (Summated Xersotomia Inventory-Dutch Version). Subjects of 2 people over the age of 30 years. The intervention was done in the form of chewing 2 grains of xylitol gum 3 times a day after a large meal and brushing his teeth for 2 consecutive weeks. The results of case studies on subject 1 showed a decrease in xerostomia before being given the first hemodialysis measurement intervention, namely 23 severe xerostomia, on the last day of intervention, 7 mild xerostomia. In subject 2 there was a decrease in xerostomia before the first. gum administration is recommended as a nursing intervention in the management of patients with hemodialysis measurement intervention was given, 23 severe xerostomia, on the last day of intervention, 10 mild xerostomia. The application of xylitol xerostomia.

Abstract CT015: Safety and long-term efficacy of radioligand therapy using Lu-177 labeled PSMA ligands in metastatic prostate cancer: A single center experience over 5 years

Abstract Aim: Metastatic prostate cancer (mPC) has still a poor prognosis. First- and second-line chemotherapy with docetaxel or cabazitaxel is often toxic and prolongs life by only a few months. Also novel agents like abiraterone, enzalutamide or Ra-223-chloride confer a limited survival benefit. Prostate-specific membrane antigen (PSMA) is a glutamate carboxypeptidase II overexpressed especially in poorly differentiated prostate cancer (1) and is a very attractive target for diagnosis and therapy (theranostics) with radiolabeled small molecules. Internalization and retention within the tumor cell provides very promising and highly selective treatment effects of multiple metastases with PSMA radioligand therapy (PRLT) (2-5). Methods: 224 mPC patients (mean age 71 years, mean Gleason score 8), screened by Ga-68 PSMA or F-18 DCFPyl PET/CT imaging, were treated with 1 - 9 cycles (3.5 - 12 GBq Lu-177 PSMA per cycle) between April 2013 and October 2017 and included in the intention to treat analysis with a median follow-up time of 16 months (3 - 55). Previous treatments were surgery (154), external beam radiation (151), chemotherapy (110), androgen deprivation (206) and Ra-223 chloride (19). The serum prostate antigen (PSA) levels were monitored before and after therapy. Response to therapy was also determined by RECIST as well as according to molecular imaging criteria using standardized uptake values (SUV) on Ga-68 PSMA PET/CT studies. Hematological and organ toxicity was documented according to CTCAE v4.03. Results: Reduction in serum PSA was observed in 157/224 (70%) patients; 121/224 patients (54%) demonstrated a PSA decline by &amp;gt;50%, best response was complete remission with undetectable PSA. Ga-68 PSMA PET/CT after at least 2 PRLT cycles in 200 patients demonstrated complete remission in 6 (3%), partial remission in 70 (35%), stable disease in 55 (27.5%) and progressive disease in 69 (34.5%) patients. RECIST revealed 46 (23%) partial remissions, 6 (3%) complete remissions, 84 (42%) with stable disease and 64 (32%) disease progressions. The median overall survival was 27 months. Median progression-free survival was 18 months. No severe (G3-4) bone marrow toxicity was observed and patients didn't show any evidence of nephrotoxicity or any other significant organ toxicity. Mild xerostomia occurred in less than 3% of all patients. Conclusion: Lu-177 PSMA radioligand therapy appears to be effective for the treatment of metastatic prostate cancer with only minimal toxicity, offering a significant benefit in overall and progression-free survival even in patients whose disease had progressed despite all standard treatments. Randomized controlled studies are required to best determine the place of this theranostic approach in the management of mPC. Citation Format: Harshad R. Kulkarni, Thomas Langbein, C Atay, Aviral Singh, Christiane Schuchardt, Coline Lehmann, Martin Pomper, Kenneth J. Pienta, Richard P. Baum. Safety and long-term efficacy of radioligand therapy using Lu-177 labeled PSMA ligands in metastatic prostate cancer: A single center experience over 5 years [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT015.

Clinical outcomes and toxicity after exclusive versus postoperative radiotherapy in supraglottic cancer: new solutions for old problems? The case of stage III and IV disease.

To compare toxicity, survival and laryngeal preservation rate after radiotherapy alone (RR), radiotherapy after supraglottic horizontal laryngectomy (SHLR) and radiotherapy after total laryngectomy (TLR) for advanced supraglottic laryngeal cancer. From 1984 to 2012, 532 patients (pts) were treated in our Department: 273 were potentially fit for conservative surgery (Group I) and 259 were not amenable to partial surgery (Group II). A younger age (p = 0.005), a better performance status (p < 0.001), the absence of comorbidities (p < 0.001) and the absence of nodal involvement (p = 0.006) favorably impacted on overall survival. More high-grade mucositis (p = 0.009), mild dysphagia (p < 0.001) and mild xerostomia (p < 0.001) were found in RR group; surgical patients had more edema of neck (p = 0.009) and skin toxicity (p = 0.008). Group I No differences in local, nodal and distant recurrences and in number of rescue laryngectomies were observed. The disease characteristics (T, N and stage) but not the treatment modality impacted on disease-free survival (DFS). Group II There was an higher number of local (p = 0.013) and nodal (p = 0.022) recurrences after RR. DFS (p = 0.01) was longer after TLR. No differences in DFS between TLR patients and RR patients who underwent radio-chemotherapy were found. In Group I, RR results in a local-regional control and organ preservation comparable to surgical treatments, with only slight increase of late mild xerostomia and dysphagia. In Group II RR was less effective than TLR, with a significantly worse DFS. The use of concurrent radical radio-chemotherapy seems to provide comparable loco-regional control to TLR.

Xerostomia: A day and night difference

PurposeTo compare patient-reported xerostomia during daytime and during nighttime with objectively measured parotid and submandibular gland function in a cohort of head-and-neck cancer (HNC) patients treated with RT. Materials and methodsA cohort of 138 HNC patients underwent objective measurements of parotid (PF) and submandibular (SMF) gland function and completed a xerostomia questionnaire (XQ) before RT, at 6weeks, 6months and 1year after RT. No attempt was made to spare the submandibular gland(s). The XQ contained specific questions concerning the sensation of dry mouth during day- (XD) and nighttime (XN), scored on a 5-point Likert scale. Patients with no or mild (grade 1–3) xerostomia and patients with more severe (grade 4–5) complaints were grouped together. ResultsBefore RT, no association existed between dry mouth complaints and PF or SMF. At 6weeks, 6months and 1year after RT; 37%, 51% and 36% had grade 4–5 XD and 65%, 64% and 56% had grade 4–5 XN, respectively. Patients with grade 4–5 XD and XN had significantly worse SMF at all time points after RT compared to patients with grade 1–3 XD and XN, while PF was significantly worse only at 6weeks after RT. In multivariate analyses, SMF was consistently the most important factor related to XN after treatment. PF significantly influenced XD at 6weeks and 1year after RT. ConclusionsDifferentiating between complaints during day- and nighttime in xerostomia research is necessary. Dry mouth at night is a frequent problem after (parotid-sparing) RT for HNC and is explained by submandibular gland dysfunction. Sparing of the contralateral submandibular gland, in addition to parotid gland sparing, may result in improved patient-reported xerostomia.

MUC5B levels in submandibular gland saliva of patients treated with radiotherapy for head-and-neck cancer: A pilot study

BackgroundThe salivary mucin MUC5B, present in (sero)mucous secretions including submandibular gland (SMG) saliva, plays an important role in the lubrication of the oral mucosa and is thought to be related to the feeling of dry mouth. We investigated if MUC5B levels in SMG saliva could distinguish between the presence or absence of severe dry mouth complaints 12 months after radiotherapy (RT) for head-and-neck cancer (HNC).FindingsTwenty-nine HNC patients with a residual stimulated SMG secretion rate of ≥0.2 ml/10 min at 12 months after RT were analyzed. MUC5B (in U; normalized to 1) and total protein levels (mg/ml) were measured in SMG saliva at baseline and 12 months after RT using ELISA and BCA protein assay, respectively. Overall, median MUC5B levels decreased after RT from 0.12 to 0.03 U (p = 0.47). Patients were dichotomized into none/mild xerostomia (n = 12) and severe xerostomia (n = 17) based on a questionnaire completed at 12 months. SMG and whole saliva flow rates decreased after RT but were comparable in both groups. The median MUC5B level was higher in patients with no or mild xerostomia compared to patients with severe xerostomia (0.14 vs 0.01 U, p = 0.22). Half of the patients with severe xerostomia had no detectable MUC5B at 12 months after RT. No differences in total protein levels were observed.ConclusionsQualitative saliva parameters like MUC5B need further investigation in RT-induced xerostomia. This pilot study showed a trend towards lower MUC5B levels in the SMG saliva of patients with severe xerostomia 12 months after RT for HNC.

Nephrotic syndrome presenting in a patient with primary Sjögren’s syndrome: questions

Case summary A 17 year-old African American woman with a history of Sjogren’s syndrome presented with several days of periorbital and pedal edema. She also had fatigue, headache, abdominal pain, and diffuse arthralgias. She had no gross hematuria or oliguria. There were no recent sore throats or upper respiratory tract infections. She had no weight loss, night sweats, joint swelling, oral ulcerations, or rash. She had taken several doses of ibuprofen for arthralgias but was not taking any other medications. She was diagnosed with primary Sjogren’s syndrome at 11 years of age after presenting with bilateral parotitis. The diagnosis of Sjogren’s syndrome was based on the parotitis and a history of xerostomia and xerophthalmia. Schirmer’s test was abnormal (prolonged wetting time of filter paper placed in the lower eyelid), indicating abnormal tear production. Sialometry showed inadequate saliva production. Serologic markers at the time of diagnosis of Sjogren’s syndrome included normal serum C3 and C4, elevated antinuclear antibodies (ANA) of 1:2560, elevated anti-Ro/SSA antibody, negative anti-double-stranded DNA antibody, and elevated rheumatoid factor. She had a normal serum creatinine concentration of 0.7 mg/dl and a normal urinalysis with no blood or protein. She was treated with prednisone for 1 year and remained symptom free aside from intermittent mild xerostomia and xerophthalmia. Her father has systemic lupus erythematosus (SLE) and lupus nephritis.

Long term chemoradiotherapy-related dental and skeletal complications in a young female with nasopharyngeal carcinoma

We describe the long-term complications six years after chemoradiotherapy in a 20-year old woman with nasopharyngeal carcinoma. We wanted to know whether the radiation dose was constant throughout the oral cavity, and thus uniformly affecting the corresponding dental and skeletal structures. Clinical and radiologic findings are described six years after chemoradiotherapy based on a two-dimensional computerized treatment planning system. This revealed radiation caries limited only to posterior teeth, proximal caries in the anterior teeth, limited but continuous salivary flow, mild periodontal infection, mild xerostomia, and a regenerative capacity of bones and the developmental process. The quantitative assessment of radiation delivered to the mandible revealed a high radiation dose in the posterior area and a minimal dose in the anterior area. This explains the differences in caries manifestation between the anterior and posterior teeth. According to the present study, individualized radiation fields, using a two-dimensional treatment planning system, result in restriction of severe damage of the dental and skeletal structures, which usually follows chemoradiotherapy. Orthodontic treatment could be initiated according to individual patient needs.

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.

Concomitant 3D-radiotherapy (3D-RT) with cisplatin (P) for advanced paranasal sinus carcinoma

5608 Background: To determine the benefit of concomitant 3D-RT with P on locoregional control in-patients (pts) with locally advanced paranasal sinus carcinoma. Methods: 6 pts with histopathologically proven carcinoma of the maxillary sinuses and residual macroscopic tumor were treated with combined P (30 mg/m2once per week(w)) and 3D-RT. All pts had undergone surgical reduction. The isocenric 3D technique consisted of several unwedged or wedged beams using 6-MV photon beams. The prescribed total dose at the isocenter was 66–70 Gy in fraction of 2 Gy. The clinical target volume (CTV) was determined according to the CT/MRI findings of the gross tumor volume (GTV). We were considered edges of the resections and regions with residual disease in which the GTV had invaded surround structures. In those regions in which the GTV was limited by intact bone, no margin was added in that direction. In the regions in which the GTV had invaded other paranasal sinuses the whole compartment was included in the CTV. In those regions in which the GTV had invaded the orbit or extended intracranially margin of 0.5–1 sm. was added to the GTV. A 3-mm expansion margin was applied to the CTV to obtain the planning target volume (PTV). All pts were closely followed with clinical examination and control MRI scans in intervals of 6 w and 3 months (m), then 6 m after therapy. Treatment related acute and late side effects ware assessed according to the Common Toxicity Criteria (CTC). Results: Median follow-up was 10 m. One pt developed locoregional recurrence 9 m after therapy. Actuarial locoreginal control rate was 83.33%, with locoregional recurrence of 16.67%. Most common acute side effects were skin erythema CTC Grade 1 in all pts and mucositis Grade 2 and 3. Mild xerostomia was persistent in all pts. Hematological toxicity was low with anemia Grade 1 in 2 pts and leucopenia grade 2 in 3 pts. Conclusions: Our preliminary data indicate that concomitant P and 3 D-RT is feasible and effective in pts with locally advanced paranasal carcinoma. Acute and late toxicity is moderate. Here, P has radiosensitisizing potential and 3D-RT brings opportunity for substantial decrease in the irradiated volume. No significant financial relationships to disclose.

Treatment results of tonsillar lymphoma: a 10-year experience.

Primary extranodal non-Hodgkin's lymphomas of the head and neck account for 10-20% of all non-Hodgkin's lymphomas. Primary tonsillar lymphoma accounts for less than 1% of head and neck malignancies, although the tonsil is the most common primary extranodal site of head and neck non-Hodgkin's lymphomas. In this study we analyzed our cases of tonsillar lymphoma treated in our institution during the last 10 years to compare the finding of this study with those of previous studies. We reviewed the cases of tonsillar lymphoma treated in the Radiation Oncology Department of Shiraz University from 1992 to 2002. Clinical data were obtained from patients' files. The patients were treated by combined chemotherapy [a median of six cycles of a CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisolone)] and radiation therapy (40-50 Gy to the primary site and neck). Chemotherapy mainly preceded radiotherapy, although the sequence of radiotherapy and chemotherapy was determined by individual physicians and patients' choice. Surgery was used mainly to establish the diagnosis, and tonsillectomy was performed for localized small lesions. Between 1992 and 2002, 19 patients with stage IE (10), IIE (7), and IIIE (2) disease were treated. Median and mean age was 48 and 44 years (range: 22-76 years), respectively, at the time of diagnosis, with a male to female ratio of 1.2:1. The vast majority of patients presented in early stages with aggressive histology. High-grade tumors seemed to affect mainly young people (p=0.226). Diffuse large B-cell lymphomas were the most prevalent. Male patients were significantly younger than females (p=0.021). The patients were treated by combined chemotherapy and radiation therapy. All patients achieved and maintained complete remission with a median of 60 months relapse-free survival and a 5-year cause-specific survival rate of 100%. All patients developed some degree of oropharyngeal mucositis. Three patients (16%) experienced grade 3 or 4 neutropenia. Mild (grade I) xerostomia remained persistently in four patients (21%). A late fatal side effect was observed in one patient who developed radiation-induced sarcoma 7 years after initial diagnosis and died 8 months later without evidence of recurrent lymphoma. Complete follow-up was obtained in all patients. The follow-up period ranged from 18 to 141 months with a median of 60 and a mean of 60.4 months. At the time of last follow-up, all patients but one were alive. Age, sex, stage, bulk of disease, performance status, number of chemotherapy cycles, number of involved sites, histologic subtypes, and radiation dose were analyzed as prognostically significant for disease-specific survival in our cases. Significant prognostic factors were not identified by multivariate analysis. Combined chemotherapy and radiation therapy is safe, highly effective, and probably curative for most patients with primary tonsillar lymphoma.

Preservation of oral health–related quality of life and salivary flow rates after inverse-planned intensity- modulated radiotherapy (IMRT) for head-and-neck cancer

PurposeTo assess whether comprehensive bilateral neck intensity-modulated radiotherapy (IMRT) for head-and-neck cancer results in preserving of oral health–related quality of life and sparing of salivary flow in the first year after therapy. Methods and materialsTwenty-three patients with head-and-neck cancer (primary sites: nasopharynx [5], oral cavity [12], oropharynx [3], and all others [3]) were accrued to a Phase I–II trial. Inverse planning was carried out with the following treatment goals: at least 1 spared parotid gland (defined as the volume of parotid gland outside the planning target volume [PTV]) to receive a median dose of less than 20 Gy; spinal cord, maximum 45 Gy; PTV1 to receive a median dose of 50 Gy; PTV2 to receive a median dose of 60 Gy (postoperative setting, n = 15) or 66–70 Gy (definitive radiotherapy setting, n = 8). Treatment was delivered with 6 and 15 MV photons using a “step-and-shoot” technique on a Varian 2300 EX linac with 120-leaf Millenium MLC. Unstimulated and stimulated whole-mouth salivary flow rates were measured, and patients completed the University of Washington instrument (UWQOL) and a separate xerostomia questionnaire (XQOL) in follow-up. ResultsEarly functional outcome end point data are available at the 1-, 3-, and 12-month follow-up time points for 22, 22, and 18 patients, respectively. The combined mean parotid dose was 30.0 Gy (95% confidence interval: 26.9–33.1). The differences from baseline in mean overall UWQOL scores at 1, 3, and 12 months postradiotherapy were −0.24, 0.32, and 4.28, not significantly different from zero (p = 0.89, p = 0.87, p = 0.13). None of the UWQOL individual domain scores related to oral health (pain, eating-chewing, eating-swallowing, and speech) at 1, 3, or 12 months were significantly different from baseline. Both unstimulated and stimulated whole-mouth flow was variably preserved. Unstimulated salivary flow at 1 and 12 months was inversely correlated with combined mean parotid dose (p = 0.014, p = 0.0007), whereas stimulated salivary flow rates at 3 and 12 months were also correlated with combined mean parotid dose (p = 0.025, p = 0.0016). Combined maximum parotid dose was correlated with unstimulated flow rate at 12 months (p = 0.02, r = −0.56) and stimulated flow rate at 1 and 12 months (p = 0.036, r = −0.45; p = 0.0042, r = −0.66). The proportion of patients reporting total XQOL scores of 0 or 1 (no or mild xerostomia) did not diminish significantly from baseline at 1, 3, or 12 months (p = 0.72, p = 0.51, p = 1.0). Unstimulated and stimulated flow at 1 month was inversely correlated with total XQOL score at 12 months (p = 0.025, p = 0.029). ConclusionsOral health–related quality of life (HRQOL) was highly preserved in the initial 12 months after IMRT, as assessed with separate, validated instruments for xerostomia-specific quality of life and oral HRQOL. In general, patients with better-preserved unstimulated salivary flow rates tended to report lower xerostomia scores. Whole-mouth salivary flow rates post IMRT were inversely correlated with combined mean parotid doses. Longer follow-up is required to assess to what extent HRQOL is favorably maintained.

Immediate toxicity during fractionated total body irradiation as conditioning for bone marrow transplantation

Background: Total body irradiation followed by bone marrow transplantation is well established as a part of the conditioning regimen in high dose therapy. The immediate tolerance of fractionated total body irradiation (FTBI) was investigated prospectively. Methods: From January 1995 to December 1998 162 patients received a FTBI, 6×2 Gy on 3 consecutive days, lung dose 10 Gy, for allogeneic ( n=112) or autologous ( n=50) bone marrow transplantation. High dose chemotherapy (mostly Cyclophosphamide) was administered after the FTBI. A standardized supportive therapy was administered. The immediate toxicity of FTBI was evaluated prospectively prior to each radiation fraction using a defined questionnaire. Results: Main symptoms distressing the patient during irradiation period were gastrointestinal symptoms like nausea and emesis. The prevalence of nausea per fraction increased to 26.1% after the 4th fraction, with a significant higher prevalence in children younger than 10 years at 1st and 2nd fractions. 42.6 and 22.8%, respectively, of all patients complained of nausea and episodes of emesis, during FTBI. Mild xerostomia and parotiditis were observed in 29.9 and 7.1% of all patients. Further gastrointestinal side effects during FTBI were loss of appetite in 16.0%, indisposition in 25.3%, mild oesophagitis in 3.7% and diarrhoea in 3.7% of the patients. During FTBI 41.4% of the patients developed a temporary skin irritation (mild erythema). Pruritus was registered in 3.7% of the patients. Headache was observed in 14.8% and Fatigue syndrome in 49.2% of women and 28.3% of men ( P<0.005). Conclusion: FTBI is a well tolerated therapeutic regimen in high dose therapy. The 162 patients investigated revealed no severe immediate side effects.

Reduction of radiation-induced xerostomia in nasopharyngeal carcinoma using CT simulation with laser patient marking and three-field irradiation technique

Tumor control and reduction of postirradiation xerostomia in patients with nasopharyngeal carcinoma (NPC) using the three-field irradiation technique based on the CT-based simulation with laser patient marking was investigated. Seventy-eight patients with NPC were consecutively treated between 1983 and 1993. In 33 patients treated before 1987, target volume was determined using a conventional x-ray simulator with a reference of CT images, and the primary site was treated by the conventional parallel-opposed two-field technique (Group I). In 45 patients treated from 1987, target volume was determined using a CT simulator slice by slice, the treatment field was projected onto the patient's skin by a laser beam projector mounted on a C-arm, and the primary site was irradiated by a three-fields (anterior and bilateral) technique (Group II). In Group II, the shape of each field was determined using a beam's eye view to reduce the dose to the bilateral parotid glands. The three-field technique reduced the dose to the superficial lobe of parotid gland to about two-thirds of the dose given by the two-field technique. Radiation-induced xerostomia was evaluated by clinical symptoms and radioisotope sialography. The 5-year survival rate and disease-free survival rate were 46.6 and 31.2% in Group I, and 46.8 and 46.5% in Group II. A large variation in the volume of parotid glands were demonstrated, ranging from 9 cm3 to 61 cm3 among patients treated with CT simulation. Forty percent of the patients in Group II showed no or mild xerostomia, whereas all of the patients in Group I showed moderate to severe xerostomia (p < 0.01). The radioisotope sialography study showed that the mean secretion ratio by acid stimulation was improved from 3.8% in the Group I to 15.2% in the Group II (p < 0.01). CT simulation was useful to determine the size and shape of each field to reduce the dose to the parotid gland, of which size varies largely among individual patients. The three-field technique based on CT simulation with laser patient markings is suggested to result in superior complication-free survival in terms of salivary dysfunction than did the conventional two-field technique with x-ray simulatior for NPC.

Parotid gland sparing in patients undergoing bilateral head and neck irradiation: Techniques and early results

To minimize xerostomia in patients receiving bilateral head and neck irradiation (RT) by using conformal RT planning to spare a significant volume of one parotid gland from radiation. The study involved 15 patients with head and neck tumors in whom bilateral neck radiation was indicated. The major salivary glands and the targets (tumor, surgical bed, metastases to lymph nodes, and the locations of lymph nodes at risk for metastases) were outlined on axial computed tomography images. Beam's-eye view (BEV) displays were used to construct conformal beams that delivered the prescribed doses to the targets while sparing from direct radiation most of one parotid gland. The gland that was planned to be spared resided in the neck side that was judged in each patient to be at a lesser risk of metastatic disease. Major salivary gland flow rates and the responses to a subjective xerostomia questionnaire were assessed before, during, and after radiation. Radiation planning for patients with central oropharyngeal tumors required the generation of multiple axial nonopposed beams. The resulting isodoses encompassed the targets, including the retropharyngeal nodes and the jugular nodes up to the base of skull bilaterally, while limiting the dose to the oral cavity, spinal cord, and one parotid gland. For patients with lateralized tumors, the ipsilateral neck side was treated up to the base of the skull; in the contralateral neck side, the treatment included the subdigastric nodes but excluded the jugular nodes at the base of the skull and most of the parotid gland. This was accomplished by a moderate gantry angle that was chosen using the BEV displays. Three months following the completion of radiation, the spared parotid glands retained on average 50% of their unstimulated and stimulated flows. In contrast, no saliva flow was measured from the unspared glands in any of the patients. Subjective xerostomia was absent, mild, or not different from that reported before radiation in 10 of 15 patients (67%). Partial parotid gland sparing is feasible by using three-dimensional planning in patients undergoing bilateral head and neck radiation. Approximately 50% of the saliva flow from the spared glands may be retained, and most patients thus treated have no or mild xerostomia in the early period after the completion of radiation. Whether tumor control and late complications are comparable to standard radiation will be assessed as more experience is gained.

Radiation therapy as a treatment for benign lymphoepithelial parotid cysts in patients infected with human immunodefiency virus-1

Patients who are infected with the human immunodeficiency virus (HIV) may develop benign lymphoepithelial cysts within the parotid gland that cause severe facial deformity. Standard treatment for this disorder has been superficial parotidectomy, repeated fine-needle aspirations or observation alone. These approaches are unsatisfactory because elective surgery in immunocompromised patients should be avoided, the cysts recur soon after aspiration, and observation alone for a treatable deforming facial process is unacceptable. Radiotherapy's proven effectiveness in treating other benign disorders of the parotid gland led us to evaluate its usefulness as a treatment for this disorder. Eight patients with parotid enlargement, who were seropositive for HIV, received 8–10 Gy to the parotids in 1 week. Five patients had complete response and three patients had partial response. All were very satisfied with the cosmetic result. Treatment-related toxicity was well tolerated and consisted of mild xerostomia and transient taste loss. In all cases, these side effects resolved within 1 month. Radiation therapy thus appears to be an effective and well-tolerated treatment for AIDS-related parotid enlargement.

13-cis-retinoic acid induces cellular differentiation and durable remission in refractory cutaneous ki-1 lymphoma

A 35-year-old man with refractory cutaneous Ki-1 lymphoma was salvaged successfully with oral 13-cis-retinoic acid (1 mg/kg/day). He had a complete remission lasting for 20 months before a single nodule recurred on his skin. Excisional biopsy of the recurrent tumor revealed a distinct morphologic change, suggesting cellular differentiation toward a more benign phenotype. No significant side effects were noted except mild xerostomia, bone pain, and hyperlipidemia. The authors believe that 13-cis-retinoic acid should be considered in the treatment of cutaneous Ki-1 lymphoma.