Analysis of PET parameters as prognosticators of survival and tumor extent in Oropharyngeal Cancer treated with surgery and postoperative radiotherapy.

BACKGROUND: Positron-emission tomography (PET) is widely used to detect malignancies, but consensus on its prognostic value in oropharyngeal cancer has not been established. The purpose of this study was to analyze the PET parameters associated with tumor extent and survival in resectable oropharyngeal cancer. METHODS: The PET parameters in oropharyngeal cancer patients with regional node metastasis who underwent surgery and postoperative radiotherapy between January 2005 and January 2019 were analyzed. We calculated the SUVmax, tumor-to-liver ratio (TLR), metabolic tumor volume (MTV, volume over SUV 2.5), and total lesion glycolysis (TLG, MTV x mean SUV) of the primary lesion and metastatic nodes. Histologic findings, patient survival, and recurrence were reviewed in the medical records. RESULTS: Fifty patients were included, and the PET parameters were extracted for 50 primary lesions and 104 nodal lesions. In the survival analysis, MTV and TLG of the primary lesions showed significant differences in overall survival (OS) and recurrence-free survival (RFS). In the multiple regression analysis, TLG of the primary lesion was associated with the depth of invasion (DOI). MTV of the nodes was a significant factor affecting extranodal extension (ENE). CONCLUSIONS: PET parameters could be related with OS, RFS, DOI of the primary tumor, and ENE. PET would be expected to be a useful diagnostic tool as a prognosticator of survival and pathologic findings in oropharyngeal cancer.

Influence of remoteness of residence on timeliness of diagnosis and treatment of oral cavity and oropharynx cancer: A retrospective cohort study.

INTRODUCTION: Geographic disparities in head and neck cancer (HNC) outcomes in Australia may be mediated by timeliness of diagnosis and treatment. This retrospective cohort study examines geographic variations in survival and time intervals leading up to treatment for HNC at two tertiary referral centres in New South Wales. METHODS: Eligible patients were NSW residents aged ≥18 years, diagnosed with primary oropharynx or oral cavity squamous cell carcinoma (SCC) between 01 July 2008 and 30 June 2013, and treated with curative intent. Main outcomes were times from diagnosis to treatment and from surgery to post-operative radiotherapy and overall survival. Differences based on remoteness of residence (regional/remote or metropolitan) were assessed. RESULTS: A total of 224 patients were eligible. Median time from symptom onset to treatment was longer for regional/remote patients with oropharynx SCC (4.7 vs. 3.8 months, P = 0.044) and oral cavity SCC (6.4 vs. 3.3 months, P = 0.003). Median time from diagnosis to treatment was longer for regional/remote patients with oropharyngeal SCC (47 days vs. 36 days, P = 0.003). Time from surgery to adjuvant radiotherapy was longer among regional/remote patients with oral cavity SCC (66 vs. 42 days, P = 0.001). Overall survival did not differ based on remoteness. CONCLUSION: Regional/remote HNC patients experienced longer times to diagnosis and treatment, and regardless of remoteness of residence, fewer than half of patients were treated within guideline recommended timeframes. Despite this non-adherence to guidelines, there were no differences in survival outcomes among this cohort. However, the impact of not meeting guidelines on patient outcomes other than survival warrants further investigation.

Treatment outcomes in oropharynx cancer patients who did not complete planned curative radiotherapy.

PURPOSE: To evaluate outcomes in oropharyngeal cancer (OPC) patients who did not complete their planned curative radiation therapy (RT). METHODS: OPC Patients who received less than planned curative RT dose between 2002 and 2016 were identified for analysis. HPV status was assessed. Radiation dose was normalized for fractionation variations using biological effective doses assuming tumor α/ß = 10 Gy [BED10]. Outcomes were compared using BED10. Multivariable and univariable analysis identified OS predictors. RESULTS: From a total of 80 patients who did not complete therapy, 64 patients were eligible for analysis. RT incompletion was due to: RT side effects (n = 23), patients' decision (n = 21), disease progression or metastases (n = 3), and other causes (n = 7). Median BED10 (Gy) was 56.2 for the HPV-positive and 58 for the HPV-negative. Three-year OS was 74% vs 13% (p < 0.001) for the HPV-positive (n = 29) and HPV-negative (n = 24), respectively. HPV-positive patients who received BED10 ≥55 had higher OS than those received BED10 <55 (94% vs 47%, p = 0.002) while no difference in OS by BED10 ≥55 vs <55 for the HPV-negative (12 vs 13%, p = NS). HPV-positive status was associated with a higher OS (HR 12.5, 95% CI, 4.54 to 33.3, p < 0.001). A total of 37 patients were available to estimate TD50 for local control assessment. TD50 (BED10) was estimated at 60.5 Gy for HPV-negative patients compared to 27.2 Gy for HPV-positive patients. CONCLUSION: Overall, in patients with incomplete treatment, HPV-positive OPC patients demonstrated a better OS compared to HPV-negative patients. HPV-positive patients who received BED10 ≥55 have higher rates of OS.

Characterization and radiosensitivity of HPV-related oropharyngeal squamous cell carcinoma patient-derived xenografts.

Background: Oropharyngeal squamous cell carcinomas (OPSCC) are rising rapidly in incidence due to Human Papillomavirus (HPV) and/or tobacco smoking. Prognosis is better for patients with HPV-positive disease, but may also be influenced by tobacco smoking and other factors. There is a need to individualize treatment to minimize morbidity and improve prognosis. Patient-derived xenografts (PDX) is an emerging pre-clinical research model that may more accurately reflect the human disease, and is an attractive platform to study disease biology and develop treatments and biomarkers. In this study we describe the establishment of PDX models, compare PDX tumors to the human original, and assess the suitability of this model for radiotherapy research and biomarker development. Material and methods: Tumor biopsies from 34 patients with previously untreated OPSCC were implanted in immunodeficient mice, giving rise to 12 squamous cell carcinoma PDX models (7 HPV+, 5 HPV-). Primary and PDX tumors were characterized extensively, examining histology, immunohistochemistry, cancer gene sequencing and gene expression analysis. Radiosensitivity was assessed in vivo in a growth delay assay. Results: Established PDX models maintained histological and immunohistochemical characteristics as well as HPV-status of the primary tumor. Important cancer driver gene mutations, e.g., in TP53, PIK3CA and others, were preserved. Gene expression related to cancer stem cell markers and gene expression subtype were preserved, while gene expression related to hypoxia and immune response differed. Radiosensitivity studies showed high concordance with clinical observations. Conclusion: PDX from OPSCC preserves important molecular characteristics of the human primary tumor. Radiosensitivity were in accordance with clinically observed treatment response. The PDX model is a clinically relevant surrogate model of head and neck cancer. Perspectives include increased understanding of disease biology, which could lead to development of novel treatments and biomarkers.

Priorities of human papillomavirus-associated oropharyngeal cancer patients at diagnosis and after treatment.

INTRODUCTION: Little is known regarding how human papillomavirus-positive oropharyngeal cancer (HPV-OPC) patient goals change with treatment. This study evaluates whether patient ranking of non-oncologic priorities relative to cure and survival shift after treatment as compared to priorities at diagnosis. MATERIALS AND METHODS: This is a prospective study of HPV-OPC patient survey responses at diagnosis and after treatment. The relative importance of 12 treatment-related priorities was ranked on an ordinal scale (1 as highest). Median rank (MR) was compared using Wilcoxon matched-pairs signed-rank tests. Prevalence of high concern for 11 treatment-related issues was compared using paired t-test. The effect of patient characteristics on change in priority rank and concern was evaluated using linear regression. RESULTS: Among 37 patients, patient priorities were generally unchanged after treatment compared with at diagnosis, with cure and survival persistently ranked top priority. Having a moist mouth uniquely rose in importance after treatment. Patient characteristics largely did not affect change in priority rank. Concerns decreased after treatment, except concern regarding recurrence. DISCUSSION: Treatment-related priorities are largely similar at diagnosis and after treatment regardless of patient characteristics. The treatment experience does not result in a shift of priorities from cure and survival to non-oncologic domains over cure and survival. The rise in importance of moist mouth implies that xerostomia may have been underappreciated as a sequelae of treatment. A decrease in most treatment-related concerns is encouraging, whereas the persistence of specific areas of concern may inform patient counseling.

Tumor volume as a prognostic marker in p16-positive and p16-negative oropharyngeal cancer patients treated with definitive intensity-modulated radiotherapy.

PURPOSE: To investigate the impact of primary gross tumor volume (pGTV) and nodal gross tumor volume (nGTV) in oropharyngeal squamous cell carcinoma (OPSCC) and the difference in their role between human papillomavirus (HPV)-positive and HPV-negative patients. METHODS: The patient cohort consists of 91 OPSCC patients treated with definitive radiochemotherapy or radiotherapy using intensity-modulated radiotherapy (IMRT). All patients had a minimum follow-up of 31 months. Volume measurements were made from computer tomography (CT) scans and HPV status was assessed by p16 immunohistochemistry. The end points were as follows: overall survival (OS), disease-free survival (DFS) and locoregional control (LRC). RESULTS: pGTV was a significant independent prognostic factor for overall survival (OS; p = 0.020) in p16-negative patients. nGTV of p16-negative tumors had significant prognostic value in all end points in multivariate analyses. High-stage (III-IVc) p16-negative tumors were only associated with significantly poorer OS (p = 0.046) but not with poorer LRC or DFS when compared with the low-stage (I-II) tumors. nGTV of p16-positive tumors was an independent prognostic factor for DFS (p = 0.005) and LRC (p = 0.007) in multivariate analyses. CONCLUSION: pGTV may serve as an independent prognostic factor in p16-negative patients and nGTV may serve as an independent prognostic factor both in p16-positive and p16-negative patients treated with radiochemotherapy or radiotherapy using IMRT. Tumor volume may have an impact on selecting patients for de-escalation protocols in the future, both in p16-positive and p16-negative patients.

Comparison of conventional fractionation (five fractions per week) and altered fractionation (six fractions per week) in stage I and II squamous cell carcinoma of oropharynx: An institutional study.

BACKGROUND: The radiotherapy (RT) dose and fractionation schedule for head and neck cancers for locoregional control and acceptable organ toxicity are still debatable. Accelerated RT includes administration of six fractions per week with the same dose per fraction. AIM: Comparison of conventional versus accelerated RT in terms of locoregional control, and acute and late radiation toxicity in squamous cell carcinoma oropharynx (stage I and II). SETTINGS AND DESIGN: Prospective, double arm, phase 2, randomized study. MATERIALS AND METHODS: Sixty patients of squamous cell carcinoma oropharynx (stage I and II) were randomized in two arms (accelerated fractionation, arm 1 and conventional fractionation, arm 2). All patients received RT dose of 66 Gray (Gy) in 33 fractions (#). The patients in arm 1 received six fractions per week with 2 Gy/# (Monday-Saturday) and in arm 2, five fractions per week with 2 Gy/# (Monday-Friday). No chemotherapy was administered. During and after the treatment, locoregional control, and acute and late radiation toxicity were assessed. RESULTS: At 1-year follow-up, 76% patients in arm 1 and 64% patients in arm 2 had complete response. The recurrence rate at the end of 1 year in arm 1 was 12% and it was 20% in arm 2.The acute Grade 2 and 3 toxicities were higher in the accelerated arm and no significant difference in late toxicities was found. SPSS version 4.0 was used for statistical analysis. CONCLUSION: Accelerated fractionation provides better locoregional control with higher but acceptable acute and equal late radiation toxicity in squamous cell carcinoma oropharynx.

Assessment of indomethacin oral spray for the treatment of oropharyngeal mucositis-induced pain during anticancer therapy.

PURPOSE: The efficacy and safety of indomethacin (IM) oral spray (OS) as a pain control therapy for oropharyngeal mucositis due to anticancer chemo- and radiotherapy were assessed in patients with head and neck carcinomas and haematological tumours. METHOD: We observed 35 patients (male/female, 20/15; 53 ± 17 years) with oropharyngeal mucositis who were treated with IM-OS preparation for pain relief at University of Tsukuba Hospital, Japan. Analgesic effects were assessed using the six-grade face scale for pain in 28 patients at the start of IM oral spray treatment. Systemic exposure was assessed by determining urinary excretions of IM in seven patients. RESULTS: Pain relief was achieved in 26 (93%) patients at 25 (5-60) min after applying the IM-OS preparation (15.6 ± 3.4 µg/kg) and analgesic effects were maintained for 120 (10-360) min. The pain was significantly decreased after using the spray (3.6 ± 0.7 vs. 2.4 ± 0.9, p < 0.01). Moreover, urinary IM excretion rates after applying the IM spray preparation were 1.8 ± 0.8% of the IM oral spray dose (130.5 ± 77.7 µg/kg/day), which was markedly lower than that following oral administration of IM (60%). No adverse events were observed following application of the spray. CONCLUSIONS: The present IM spray is an effective and safe preparation for pain relief and can be used as an alternative therapeutic option for oropharyngeal mucositis in cancer patients.

Definitive Intensity-modulated Radiation Therapy in Elderly Patients with Locally Advanced Oropharyngeal Cancer.

BACKGROUND: To evaluate the treatment tolerance and clinical outcomes in patients aged 70 years and older with locally advanced oropharyngeal cancer treated by definitive intensity-modulated radiation therapy (IMRT). PATIENTS AND METHODS: We retrospectively analyzed 15 consecutive elderly patients, with histologically-proven squamous cell carcinoma of the oropharynx, staged T3-4 with or without involved lymph nodes at diagnosis, who received definitive sequential IMRT (70 Gy; 2 Gy/fraction). Adult Comorbidity Evaluation-27 (ACE-27) score was calculated and its influence on treatment tolerance and clinical outcomes was analyzed. RESULTS: A total of 15 patients were included with a median age of 77 years (range=70-88 years). At baseline, 8 patients (53.3%) had an ACE-27 score of 1, and the remainder (n=7, 46.7%) had a comorbidity index of 0. All patients completed programmed IMRT treatment, without any reduction of total dose. Oral pain and mucositis were the most common acute side-effects, classified as grade 3 in 6 patients (40%) only. Xerostomia was reported in 13 patients (86.7%), without severe manifestation. There was no hematological toxicity. ACE-27 score was not related to higher severe acute toxicity. No patients experienced grade 3 or more late toxicity. Five-year overall survival and disease-free survival rates were 63.6% (95% confidence interval=32.7-83.3%) and 55% (95% confidence interval=24.4-77.6%), respectively. Comorbidity score did not influence survival outcomes, both overall survival (p=0.46) and disease-free survival (p=0.55). CONCLUSION: Treatment tolerance, as well as survival outcomes were good in elderly oropharyngeal cancer patients treated with definitive sequential IMRT. Due to age and comorbidity, no dose or volume reduction for IMRT should be considered in this setting of patients. A prospective randomized trial with a large sample size should be conducted to confirm our results.

Photobiomodulation therapy: management of mucosal necrosis of the oropharynx in previously treated head and neck cancer patients.

Necrosis of the oral mucosa following head and neck cancer radiation therapy presents considerable clinical management challenges. We report three cases of symptomatic persisting oral ulcerations where the addition of photobiomodulation therapy resulted in a rapid resolution of the oral lesions and in patient symptoms. These cases suggest that photobiomodulation may represent an adjunct to care of these difficult to manage complications in oncology.

Randomized clinical trial on 7-days-a-week post-operative radiotherapy vs concurrent post-operative radiochemotherapy in locally advanced cancer of the oral cavity/oropharynx: a report on acute normal tissue reactions.

OBJECTIVE: The purpose of the study was to evaluate acute normal tissue reactions and treatment compliance in a randomized clinical trial on 7-days-a-week post-operative radiotherapy (p-CAIR) vs post-operative concurrent radiochemotherapy (p-RTCT) in locally advanced cancer of the oral cavity/oropharynx. The sample analyzed at present represents approximately 30% of the intended future trial size. METHODS: The patients were randomly assigned to receive 63 Gy in 1.8-Gy fractions 7 days a week (n = 44) or 63 Gy in 1.8-Gy fractions 5 days a week with concurrent cisplatin 80-100 mg per square metre of body surface area on Days 1, 22 and 43 of the course of radiotherapy (n = 40). Acute mucosal reactions were scored using the modified Dische system. RESULTS: 15 (17.9%) patients, including 5 patients in p-CAIR and 10 patients in p-RTCT, did not comply with the assigned radiation treatment, mostly because of rapid tumour progression or deteriorating general performance. In p-RTCT, 22 (55%) patients received less than the intended three courses of chemotherapy mostly owing to haematological toxicity. The average maximum mucosal severity score was 14.2 in p-CAIR compared with 13.4 in p-RTCT; the difference was not statistically significant (p = 0.31). CONCLUSION: The schedules compared (p-CAIR and p-RTCT) did not differ considerably with respect to acute mucosal reactions. Haematological toxicity in p-RTCT was elevated compared with p-CAIR. Both schedules were considered tolerable with respect to acute toxicity, which justifies further recruitment to the trial. ADVANCES IN KNOWLEDGE: The results show that early mucosal reactions are comparable in both trial arms but haematological toxicity is more pronounced during radiochemotherapy.

Thermal tomography imaging in photonic traditional Chinese medicine information therapy with holistic effect for health whole nursing.

A photonic traditional Chinese medicine (TCM) information therapy was developed that has applications in whole health nursing including the prevention and treatment of ischemic cardiovascular and cerebrovascular diseases as well as the conditioning of the subhealth state. This therapy utilizes the beam of a 630 nm LED light to irradiate the oropharynx, while simultaneously employing two beams of 650 nm LED light to irradiate corresponding acupuncture points resulting in a synergistic outcome. This method was named "1 + 2 phototherapy." The principle mechanism of the therapy is a series of photon induced biological effects that are triggered by stimulating the photosensitive tissues of the oropharynx. This tissue includes the oral mucosa, capillaries, lymph nodes, saliva glands, nerves, and Jingluo and is stimulated by light beams of certain photon energy and imitative acupuncture information. Thermal tomography imaging shows that the average temperature of the upper-body was improved significantly after oropharyngeal irradiation under irradiation of "Futu point": the heat radiation of the spine, as well as chest, shoulders, arms, and clavicle, increased under irradiation of "Hoku," whereas the overall average temperature was below the temperature before irradiation. The experiment indicates that this therapy can promote blood circulation, regulate varied physiological parameters, and have holistic effects in whole health nursing.

Radiotherapeutic treatment of a fighter pilot with nasopharyngeal carcinoma.

BACKGROUND: Radiotherapy is the standard and most effective treatment for nasopharyngeal carcinoma (NPC) in its early stages. However, its application in fighter pilots returning to flying duties with NPC has not been previously reported, presumably due to post-radiotherapeutic complications. CASE REPORT: A 36-yr-old male fighter pilot had a painless mass in the left neck for 5 mo. Pathological diagnosis demonstrated nonkeratinizing squamous cell carcinoma in the left nasopharynx which had metastasized to lymph nodes in the left side of the neck. He was diagnosed and staged with NPC (T1N2M0) before treatment with radiotherapy and adjuvant chemotherapy. The patient suffered from catarrhal otitis media and xerostomia after 3 mo of radiotherapy, but these symptoms resolved. After a total of 8 mo of radiotherapy, he was in remission with no evidence of tumor recurrence or metastasis. He had normal Eustachian tube, hearing, and vestibular function before and after hypobaric chamber testing and passed all flight-related physical examinations. Consequently, he was granted a medical waiver and returned to flying status in two-seat fighter aircraft, flying for 53 h in a 12-mo period. After passing all flight-related tests again, he was then allowed to fly in single-seat aircraft. At the time of submission of this article, he has flown for 147 h and remained on flying status for 26 mo. He will be monitored annually for long-term effects of radiotherapy and/or disease recurrence. CONCLUSIONS: Fighter pilots with NPC may be safely considered for medical waiver with appropriate monitoring after successful treatment.

Initial experience with oropharynx-targeted radiation therapy for metastatic squamous cell carcinoma of unknown primary of the head and neck.

AIM: Metastasis of unknown primary (MUP) is commonly treated with radiation therapy (RT) to the entire mucosal surfaces and bilateral neck nodes (LN). We report outcomes of oropharynx-targeted RT, retropharyngeal nodes (RPN) and bilateral LN in this context. PATIENTS AND METHODS: Single-Institution retrospective study of 68 patients. Forty percent were treated with intensity-modulated radiation therapy (IMRT). Fifty-six percent received concurrent chemoradiotherapy (CCRT). The median age was 58 years, 82% were Caucasian, and 75% males. Stage III disease was present in 9%, stage IVA in 75% and IVB in 16%. RESULTS: At a median follow-up of 3.5 years, the actuarial locoregional control was 95.5%. The emergence of primary developed in 1patient (1.5%) and 2patients (3%) failed in the neck. The median time-to-locoregional failure (LRF) was 18 months. Actuarial long-term RT toxicity was grade 1 xerostomia (68%), dysphagia (35%), neck stiffness (15%) and trismus (6%). CONCLUSION: RT to the oropharynx, RPN, and bilateral neck provides excellent oncological and functional outcomes in MUP in non-Asian patients. Sparing the mucosal surfaces of the nasopharynx, hypopharynx, and larynx seems reasonable without impacting on survival and locoregional control.

Effect of recombinant human deoxyribonuclease on oropharyngeal secretions in patients with head-and-neck cancers treated with radiochemotherapy.

PURPOSE: The current study examined the effect of recombinant human deoxyribonuclease (rhDNase) on quality of life (QOL) measures, clinical improvement, and DNA content of thick oropharyngeal secretions (OPS) in patients with head-and-neck (H&N) cancers. METHODS AND MATERIALS: Thirty-six patients with local-regional advanced H&N cancer receiving chemoradiationtherapy (CRT) were randomized to receive either placebo or rhDNase. Endpoints included MD Anderson Symptom Inventory-Head and Neck (MDASI-HN) and Functional Assessment of Cancer Therapy-Head and Neck (FACT-NH) scores, along with clinical assessment and DNA concentration of OPS. RESULTS: There were no statistically significant differences in patients' QOL outcomes over the study period. Both groups showed an increase in symptom and interference scores, although patients in the rhDNase group showed a greater decline in both scores during the 3 months posttreatment. Similarly, both groups showed a decline in physical and functional well being but recovered in the 3 months posttreatment follow-up, with the rhDNase group exhibiting speedier recovery. Patients in the rhDNase group exhibited significant clinical improvement in OPS, blindly assessed by a physician, compared with the placebo group (67% vs 27%, respectively; P=.046). The rhDNase group showed no change in OPS-DNA concentration, although the placebo group showed a significant increase in DNA concentration during the drug trial (P=.045). There was no differences in acute toxicities between the 2 groups. CONCLUSIONS: Our preliminary data suggest that rhDNase did not significantly improve study primary endpoints of QOL measures compared with the placebo group. However, there was a significant improvement in secondary endpoints of clinically assessed OPS and DNA concentration compared with placebo in H&N cancer patients treated with CRT. Further investigation in larger numbers of patients is warranted.

Spine radiosurgery: a dosimetric analysis in 124 patients who received 18 Gy.

PURPOSE: To define the safely tolerated doses to organs at risk (OARs) adjacent to the target volume (TV) of spine radiosurgery (SRS) with 18-Gy in a single fraction. METHODS AND MATERIALS: A total of 124 patient cases with 165 spine metastases were reviewed. An 18-Gy single-fraction regimen was prescribed to the 90% isodose line encompassing the TV. A constraint of 10 Gy to 10% of the spinal cord outlined 6 mm above and below the TV was used. Dosimetric data to OARs were analyzed. RESULTS: A total of 124 patients (100%) were followed-up, and median follow-up time was 7 months (1-50 months). Symptoms and local control were achieved in 114 patients (92%). Acute Radiation Therapy Oncology Group (RTOG) grade 1 oral mucositis occurred in 11 of 11 (100%) patients at risk for oropharyngeal toxicity after cervical spine treatment. There were no RTOG grade 2-4 acute or late complications. Median TV was 43.2 cc (5.3-175.4 cc) and 90% of the TV received median dose of 19 Gy (17-19.8 Gy). Median (range) of spinal cord maximum dose (Dmax), dose to spinal cord 0.35 cc (Dsc0.35), and cord volume receiving 10 Gy (Vsc10) were 13.8 Gy (5.4-21 Gy), 8.9 Gy (2.6-11.4 Gy) and 0.33 cc (0-1.6 cc), respectively. Other OARs were evaluated when in proximity to the TV. Esophagus (n=58), trachea (n=28), oropharynx (n=11), and kidneys (n=34) received median (range) V10 and V15 of 3.1 cc (0-5.8 cc) and 1.2 cc (0-2.9 cc), 2.8 cc (0-4.9 cc), and 0.8 cc (0-2.1 cc), 3.4 cc (0-6.2 cc) and 1.6 cc (0-3.2 cc), 0.3 cc (0-0.8 cc) and 0.08 cc (0-0.1 cc), respectively. CONCLUSIONS: Cord Dmax of 14 Gy and D0.35 of 10 Gy are safe dose constraints for 18-Gy single-fraction SRS. Esophagus V10 of 3 cc and V15 of 1 cc, trachea V10 of 3 cc, and V15 of 1 cc, oropharynx V10 of 3.5 cc and V15 of 1.5 cc, kidney V10 of 0.3 cc, and V15 of 0.1 cc are planning guidelines when these OARs are in proximity to the TV.

Biological mechanisms of normal tissue damage: importance for the design of NTCP models.

The normal tissue complication probability (NTCP) models that are currently being proposed for estimation of risk of harm following radiotherapy are mainly based on simplified empirical models, consisting of dose distribution parameters, possibly combined with clinical or other treatment-related factors. These are fitted to data from retrospective or prospective clinical studies. Although these models sometimes provide useful guidance for clinical practice, their predictive power on individuals seems to be limited. This paper examines the radiobiological mechanisms underlying the most important complications induced by radiotherapy, with the aim of identifying the essential parameters and functional relationships needed for effective predictive NTCP models. The clinical features of the complications are identified and reduced as much as possible into component parts. In a second step, experimental and clinical data are considered in order to identify the gross anatomical structures involved, and which dose distributions lead to these complications. Finally, the pathogenic pathways and cellular and more specific anatomical parameters that have to be considered in this pathway are determined. This analysis is carried out for some of the most critical organs and sites in radiotherapy, i.e. spinal cord, lung, rectum, oropharynx and heart. Signs and symptoms of severe late normal tissue complications present a very variable picture in the different organs at risk. Only in rare instances is the entire organ the critical target which elicits the particular complication. Moreover, the biological mechanisms that are involved in the pathogenesis differ between the different complications, even in the same organ. Different mechanisms are likely to be related to different shapes of dose effect relationships and different relationships between dose per fraction, dose rate, and overall treatment time and effects. There is good reason to conclude that each type of late complication after radiotherapy depends on its own specific mechanism which is triggered by the radiation exposure of particular structures or sub-volumes of (or related to) the respective organ at risk. Hence each complication will need the development of an NTCP model designed to accommodate this structure.

A double-blind, placebo-controlled, randomised trial of active manuka honey and standard oral care for radiation-induced oral mucositis.

Our aim was to investigate the effect of active manuka honey on radiation-induced mucositis. A total of 131 patients diagnosed with head and neck cancer who were having radiotherapy to the oral cavity or oropharyngeal area were recruited into the study, and were randomly allocated to take either manuka honey or placebo (golden syrup) 20 ml 4 times daily for 6 weeks. Mucositis was assessed according to the Radiation Therapy Oncology Group (RTOG) scale at baseline, weekly during radiotherapy, and twice weekly thereafter until the mucositis resolved. The patient's weight was recorded at the same time as the mucositis was assessed. Throat swabs to identify bacterial or fungal infections were taken at baseline, and during and after radiotherapy. There was no significant difference between honey and golden syrup in their effects on mucositis. Active manuka honey did not improve mucositis, but both the honey and the syrup seemed to be associated with a reduction in bacterial infections. Compliance was a problem after the onset of mucositis, which may have affected the findings.

Fixed number of segments in unidirectional decompositions of fluence matrices for step-and-shoot IMRT.

The decomposition of a fluence matrix in step-and-shoot mode for intensity-modulated radiation therapy (IMRT) usually yields a large number of segments (NS) and, consequently, treatment time is substantially increased. In this paper, we propose a method for reducing the original NS in multileaf collimator segmentations to a user-specified quantity. The proposed method clusters original segments into the same number of groups as desired NS, and computes for each group an equivalent segment and an associated weight. In order to avoid important changes in dose-volume histograms (DVHs), equivalent segments and weights are computed taking into account the original fluence matrix and preserving the highest fluence zones, thus staying as close as possible to the original planned radiation. The method is applicable to unidirectional segmentations, where there is no backtracking of leaves, since this property facilitates the grouping of segments. The experiments showed that treatment times can be considerably reduced, while maintaining similar DVHs and dosimetric indexes. Furthermore, the algorithm achieved an excellent reduction/dose-quality ratio since the final NS was close to that reported for direct step-and-shoot solutions.